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Guitao Wu, Xi Lin, Hua Jiang, Zhenyin Liu Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, People’s Republic of ChinaCorrespondence: Zhenyin Liu, Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong, 510623, People’s Republic of China, Email zhenyin@gwcmc.orgBackground: Venous malformation is related to genes and results in functional and morphologic anomalies. Genetic variations affecting the development of vessel endothelial cells are unclear. Therefore, this study aimed to investigate the potential value of the miR-100 rs1834306 A>G polymorphism as a marker of susceptibility to venous malformation.Methods: In this case–control study in southern Chinese children, we collected blood samples from 1158 controls and 1113 patients with venous malformation. TaqMan genotyping of miR-100 rs1834306 A>G was performed by real-time fluorescent quantitative polymerase chain reaction.Results: Multivariate logistic regression analysis showed that there was no significant association between the presence of the miR-100 rs1834306 A>G polymorphism and susceptibility to venous malformation by evaluating the values of pooled odds ratios and 95% confidence intervals. Similarly, among different sites, rs1834306 A>G was also not associated with venous malformation.Conclusion: Our results suggest that the miR-100 rs1834306 A>G polymorphism is not associated with susceptibility to venous malformation in southern Chinese children. These results need to be further confirmed by investigating a more diverse ethnic population of patients with venous malformations.Keywords: vascular malformation, susceptibility, miR-100, polymorphism

Abstract Background Neuroblastoma is a common malignant tumor stemming from the sympathetic nervous system in children, which is often life‐threatening. The genetics of neuroblastoma remains unclear. Studies have shown that miRNAs participate in the regulation of a broad spectrum of biological pathways. The abnormity in the miRNA is associated with the risk of various cancers, including neuroblastoma. However, research on the relationship of miRNA polymorphisms with neuroblastoma susceptibility is still in the initial stage. Methods In this research, a retrospective case–control study was conducted to explore whether miR‐100 rs1834306 A > G polymorphism is associated with neuroblastoma susceptibility. We enrolled 402 cases and 473 controls for the study. The logistic regression analysis was adopted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between miR‐100 rs1834306 A > G and neuroblastoma risk. Results Our results elucidated that the miR‐100 rs1834306 A > G polymorphism was associated with the decreased risk of neuroblastoma (AG versus AA: adjusted OR = 0.72, 95% CI = 0.53–0.98, and P = 0.038). The subsequent stratified analysis further found that rs1834306 AG/GG genotype reduced the risk of neuroblastoma in the subgroup with tumors of the mediastinum origin (adjusted OR = 0.63, 95% CI = 0.41–0.95, and P = 0.029). Conclusions In summary, miR‐100 rs1834306 A > G polymorphism was shown to associate with decreased neuroblastoma risk in Chinese children, especially for neuroblastoma of mediastinum origin. This conclusion needs to be verified in additional large‐size case–control studies.

Objective: To investigate the expression of long chain non coding RNA-MIR100HG（lncRNA-MIR100HG） and microribonucleic acid-100（mi R-100） in serum exosomes of patients with gastric cancer, and analyze the correlation between them and clinical pathological characteristics and progression free survival rate. Methods: Blood samples from 60 patients with gastric cancer and60 patients with benign diseases were collected, and the exosomes were extracted. The expression of lncRNA-MIR100HG/miR-100 was detected and compared between groups. Pearson correlation was used to analyze the correlation between the expression level of lncRNA-MIR100HG and mi R-100, single factor chi square test was used to analyze the correlation with the clinicopathological characteristics of gastric cancer patients, and Kaplan-Meier survival was used to analyze the expression of lncRNA-MIR100HG/miR-100and the progression free survival rate. Results:（1） The level of serum lncRNA-MIR100HG in patients with gastric cancer was higher than that in patients with gastric cancer, and the relative expression level of mi R-100 was lower than that in patients with benign gastric diseases（P＜0.05）;（2） Pearson correlation analysis showed that there was a negative correlation between serum lncRNA-MIR100HG and mi R-100（r=-0.483, P＜0.05）;（3） Single factor chi square analysis showed that the relative expression level of serum lncRNA-MIR100HG in gastric cancer patients was correlated with tumor size, differentiation, depth of tumor invasion, clinical stage, lymph node metastasis and distant metastasis, and the relative expression level of serum mi R-100 was correlated with tumor size, differentiation, clinical stage and lymph node metastasis（P＜0.05）;（4） PFS of gastric cancer patients with low level expression of serum lncRNA-MIR100HG and mi R-100 was longer than that of patients with high level expression（χ²=37.371, P＜0.05）, PFS of gastric cancer patients with high mi R-100 expression was longer than that of patients with low mi R-100 expression（χ²=28.631, P＜0.05）. Conclusion: The expression level of serum exosomes lncRNA-MIR100HG/miR-100 in patients with gastric cancer is increased, which is related to tumor size, tumor invasion depth, clinical stage and other pathological characteristics. High expression of lncRNA-MIR100HG and low expression of mi R-100 may indicate that the prognosis of gastric cancer patients is worse. [ABSTRACT FROM AUTHOR]

Abstract Background Cervical cancer has ranked the top one in gynecological malignancies for incidence. Radioresistance is now becoming a leading reason of recurrence. Methods Our microRNA array data indicated that the miRNA-100 level decreased significantly during radioresistance. In this study, we up-regulated miR-100 in Hela and Siha cells by using miR-100 mimics and observed proliferation and invasion. Results It turned out that with overexpression of miR-100, the cells had less invasiveness as well as proliferation. It may target gene mTOR, and it deed reduced EMT. To examine the role of miR-100 in radioresistance, there was no significant result showed by BSP. While the circCASC15 has been identified with sponge function according to RNA pull down and ISH. Conclusion The conclusions indicate miR-100 is a tumor suppressor gene and could be a therapeutic target in radio-resistant cervical cancers.

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of insults, such as bacterial and viral infections, including SARS-CoV-2, leading to high mortality. In the murine model of ARDS induced by Staphylococcal enterotoxin-B (SEB), our previous studies showed that while SEB triggered 100% mortality, treatment with Resveratrol (RES) completely prevented such mortality by attenuating inflammation in the lungs. In the current study, we investigated the metabolic profile of SEB-activated immune cells in the lungs following treatment with RES. RES-treated mice had higher expression of miR-100 in the lung mononuclear cells (MNCs), which targeted mTOR, leading to its decreased expression. Also, Single-cell RNA-seq (scRNA seq) unveiled the decreased expression of mTOR in a variety of immune cells in the lungs. There was also an increase in glycolytic and mitochondrial respiration in the cells from SEB + VEH group in comparison with SEB + RES group. Together these data suggested that RES alters the metabolic reprogramming of SEB-activated immune cells, through suppression of mTOR activation and its down- and upstream effects on energy metabolism. Also, miR-100 could serve as novel potential therapeutic molecule in the amelioration of ARDS.

Abstract Background Diet-induced obesity can result in the development of a diverse spectrum of cardiovascular and metabolic diseases, including type 2 diabetes, dyslipidemia, non-alcoholic liver steatosis and atherosclerotic disease. MicroRNAs have been described to be important regulators of metabolism and disease development. Methods In the current study, we investigated the effects of ubiquitous miR-100 overexpression on weight gain and the metabolic phenotype in a newly generated transgenic mouse strain under normal chow and high fat diet and used microarray expression analysis to identify new potential target genes of miR-100. Results While transgenic overexpression of miR-100 did not significantly affect weight and metabolism under a normal diet, miR-100 overexpressing mice showed a reduced weight gain under a high fat diet compared to wildtype mice, despite an equal calorie intake. This was accompanied by less visceral and subcutaneous fat development and lover serum LDL cholesterol. In addition, transgenic miR-100 mice were more glucose tolerant and insulin sensitive and demonstrated increased energy expenditure under high fat diet feeding. A comprehensive gene expression profiling revealed the differential expression of several genes involved in lipid storage- and metabolism, among them CD36 and Cyp4A14. Our data showed a direct regulation of CD36 by miR-100, leading to a reduced fatty acid uptake in primary hepatocytes overexpressing miR-100 and the downregulation of several downstream mediators of lipid metabolism such as ACC1, FABP4, FAS and PPARγ in the liver. Conclusions Our findings demonstrate a protective role of miR-100 in high fat diet induced metabolic syndrome and liver steatosis, partially mediated by the direct repression of CD36 and attenuation of hepatic lipid storage, implicating miR-100 as a possible therapeutic target in liver steatosis.

Background: Cervical cancer has ranked the top one in gynecological malignancies for incidence. Radioresistance is now becoming a leading reason of recurrence. Methods: Our microRNA array data indicated that the miRNA-100 level decreased significantly during radioresistance. In this study, we up-regulated miR-100 in Hela and Siha cells by using miR-100 mimics and observed proliferation and invasion. Results: It turned out that with overexpression of miR-100, the cells had less invasiveness as well as proliferation. It may target gene mTOR, and it deed reduced EMT. To examine the role of miR-100 in radioresistance, there was no significant result showed by BSP. While the circCASC15 has been identified with sponge function according to RNA pull down and ISH. Conclusion: The conclusions indicate miR-100 is a tumor suppressor gene and could be a therapeutic target in radio-resistant cervical cancers. [ABSTRACT FROM AUTHOR]

Objective: Thromboangiitis obliterans is a nonatherosclerotic segmental inflammatory disease, and miR-100 plays an anti-inflammatory role in chronic inflammation. Therefore, we hypothesized that miR-100 might alleviate the inflammatory damage and apoptosis of H2O2-induced ECV304 cells and aimed to investigate the relationship between miR-100 and thromboangiitis obliterans and the related molecular mechanism. Methods: Cell counting kit-8 was used to detect cell viability, and the expression of inflammatory factors and oxidative stress was measured by ELISA. TUNEL assay was used to detect the apoptosis of human umbilical vein endothelial cells after induction by H2O2. Furthermore, the interaction between miR-100 and matrix metalloproteinase-9 was verified by dual-luciferase assay. Quantitative reverse transcription polymerase chain reaction and western blot were used to detect the expression of the adhesion factors, apoptosis-related proteins and Notch pathway-related protein. Results: The results revealed that miR-100 was decreased in H2O2-induced human umbilical vein endothelial cells. Overexpression of miR-100 attenuated inflammatory response and cell apoptosis in H2O2-induced human umbilical vein endothelial cells. The overexpression of miR-100 inhibited matrix metalloproteinase-9 expression in H2O2-induced human umbilical vein endothelial cells. miR-100 inhibited H2O2-induced human umbilical vein endothelial cell inflammation, oxidative stress, and cell apoptosis via inactivation of Notch signaling by targeting matrix metalloproteinase. Conclusions: Our study demonstrated that miR-100 reduced the inflammatory damage and apoptosis of H2O2-induced human umbilical vein endothelial cells via inactivation of Notch signaling by targeting matrix metalloproteinase. These findings suggested that miR-100 might be a novel therapeutic target for the prevention of thromboangiitis obliterans. [ABSTRACT FROM AUTHOR]

Abstract Background Oral squamous cell carcinoma (OSCC) at early stages can be misdiagnosed as an oral ulcer (OU) due to similar symptoms, such as chronic and indurated ulcer. LncRNA NCK1-AS1 has been characterized as a key player in cervical cancer, while its role in OSCC is unknown. Methods All participants were selected at Jiangxi Province Tumor Hospital from December 2016 to December 2018. Expression levels of NCK1-AS1 and miR-100 in plasma from both OSCC and OU patients were measured by RT-qPCR. Diagnostic analysis was performed through ROC curve. Potential interactions between NCK1-AS1 and miR-100 were detected by cell transfection experiments. Cell invasion and migration were assessed by Transwell assays. Results The expression of NCK1-AS1 was upregulated in early-stage OSCC patients but not in OU patients. Upregulation of NCK1-AS1 distinguished OSCC patients from OU patients. The expression of miR-100 was inversely correlated with the expression of NCK1-AS1. Overexpression of NCK1-AS1 was followed by promoted OSCC cell invasion and migration. Overexpression of miR-100 did not affect the expression of NCK1-AS1 but inhibited the role of NCK1-AS1. Conclusions Therefore, NCK1-AS1 may promote the metastasis of OSCC by downregulating miR-100.

Abstract Background miR-100 is reported to be associated with cell proliferation and apoptosis. However, the function of miR-100 in mantle cell lymphoma (MCL) is unknown. The purpose of this study is to analyze the abnormal expression of miR-100 and mTOR in MCL together with their potential biological function and pathogenesis. Method Eighteen MCL tissue samples and 3 cell lines (Jeko-1, Mino, Granta-519) were investigated in this research study, while eighteen samples of proliferative lymphadenitis from patients and peripheral lymphocyte cells from healthy volunteers served as controls. The expression and alteration of miR-100 and mTOR mRNA were detected by RT-PCR. The expression and alteration of mTOR protein were explored by Western blot. LV-miR-100-up and LV-mTOR-RNAi were constructed and transfected by lentivirus transfection. Cell proliferation, cell apoptosis and the cell cycle were detected using CCK-8 and flow cytometry. Bioinformatics prediction software was used to predict the miR-100 target gene of mTOR. A double luciferase experiment was used to verify miR-100 targeting at the mTOR-3′-UTR. The interaction between miR-100 and mTOR was further studied using recovery experiments. GraphPad Prism 7 software (version 7.2) was used for statistical analysis, and a P value

Yun Zhu,* Ao Lin,* Yi Zheng, Xiaoli Xie, Qiuming He, Wei Zhong Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei ZhongDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People’s Republic of ChinaTel/ Fax +86-18902268667Email zhongwei@gwcmc.orgBackground: Hirschsprung disease (HSCR) is a rare congenital gastrointestinal disease characterized by the absence of intestinal submucosal and myometrial ganglion cells. Recently, researches indicated that miR-100 regulated the growth, differentiation and apoptosis of neurons, and affected the functions of HSCR-associated pathways. While miR-100 rs1834306 A>G polymorphism was shown to modify the susceptibility to tumors, the association between this polymorphism and HSCR susceptibility is still unknown.Methods: This was a case–control study consisting of 1470 HSCR cases and 1473 controls from southern China. DNA was genotyped by TaqMan real-time PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were used as statistical indicators.Results: We found that miR-100 rs1834306 G allele and GG genotype significantly increased HSCR susceptibility (GG vs AA: adjusted OR=1.31, 95% CI=1.04– 1.64, P=0.020; G vs A: adjusted OR=1.12, 95% CI=1.01– 1.25, P=0.041; GG vs AA/AG: adjusted OR=1.30, 95% CI=1.07– 1.59, P=0.010). In the stratified analysis, miR-100 rs1834306 GG genotype carriers had higher risk to develop HSCR in all clinical subtypes when compared with those with AA/AG genotypes, and OR was rising with HSCR aggravation (SHSCR: adjusted OR=1.28, 95% CI=1.03– 1.59, P=0.029; LHSCR: adjusted OR=1.48, 95% CI=1.06– 2.07, P=0.020; TCA: adjusted OR=2.12, 95% CI=1.22– 3.69, P=0.008).Conclusion: Our findings suggested that miR-100 rs1834306 A>G polymorphism was associated with increased HSCR susceptibility in southern Chinese children. Furthermore, miR-100 rs1834306 GG genotype had a greater genetic pathopoiesis in severe HSCR.Keywords: Hirschsprung disease, miR-100, polymorphism, susceptibility

Background Non‐small cell lung cancer (NSCLC) is a leading subtype in lung cancer, with high morbidities and mortalities worldwide. microRNA (miRNA) has appeared to play indispensable roles in a variety of solid carcinomas. The current study focused on the functions of miR‐100 in NSCLC. Methods qRT‐PCR was performed to detect miR‐100 and HOXA1 expressions in NSCLC tissues and cells. MTT and transwell assays were used to determine the functions of miR‐100 in NSCLC cell proliferation, invasion and migration abilities. Western blot was used to measure related protein expressions. Results qRT‐PCR results showed that miR‐100 expressions were dramatically decreased in NSCLC tissues. MTT assays indicated that miR‐100 restoration inhibited NSCLC cell proliferation. Furthermore, transwell assay was performed to determine the impacts of miR‐100 on NSCLC invasion and migration abilities. As expected, the invasion and migration capacities were significantly repressed. Direct interactions between HOXA1 and miR‐100 were also verified via dual‐luciferase reporter assays. Western blot analysis demonstrated that miR‐100 exerted suppressive functions via regulating EMT and Wnt/β‐catenin in NSCLC cells. Conclusions Our results showed that miR‐100 served antitumor roles in NSCLC, providing new evidence of miR‐100 as a promising therapeutic biomarker in NSCLC.

Abstract Objectives Microvesicles (MVs) derived from human Wharton’s jelly mesenchymal stem cells (MSC-MVs) were demonstrated to ameliorate acute lung injury (ALI). We have previously found that MSC-MV-transferred hepatocyte growth factor was partly involved in their therapeutic effects. Since MSC-MVs also contained a substantial quantity of miR-100, which plays an important role in lung cancer and injury, we speculated that miR-100 might similarly account for a part of the therapeutic effects of MSC-MVs. Methods MSCs were transfected with miR-100 inhibitor to downregulate miR-100 in MSC-MVs. A rat model of ALI and cell injury in rat type II alveolar epithelial cell line (L2) was induced by bleomycin (BLM). A co-culture model of alveolar epithelial cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs and mechanism. Results MSC-MV treatment attenuated BLM-induced apoptosis and inflammation in BLM-treated L2 cells and ameliorated BLM-induced lung apoptosis, inflammation, and fibrosis in BLM-induced ALI rats. The beneficial effect of MSC-MVs was partly eliminated when miR-100 was knocked down in MSCs. Moreover, MSC-MV-transferred miR-100 mediated the therapeutic effect of MSC-MVs in ALI through enhancing autophagy by targeting mTOR. Conclusion MSC-MVs enhance autophagy and ameliorate ALI partially via delivery of miR-100.

As a chronic inflammatory disease, coronary artery disease (CAD) is a common cause of death worldwide. Dysregulation of microRNA expression levels in peripheral blood mononuclear cells (PBMCs) may contribute to CAD and serve as a potential diagnostic biomarker. Here, we evaluated PBMC expression of two CAD-related inflammatory miRNAs, miR-196a and miR-100, in PBMCs of CAD patients with significant stenosis (CAD, n: 72), patients with insignificant coronary stenosis (ICAD, n: 30), and controls (n: 74) and checked whether they can segregate study groups. MiRNA expression was evaluated using the standard stem-loop RT-qPCR method. MiR-196a expression was downregulated in ICAD compared to CADs and healthy groups. MiR100 expression levels were not different between groups. The receiver operating characteristic (ROC) curve analysis acquainted that miR-196a expression levels in PBMC could segregate CAD individuals or any of its clinical manifestations (i.e. unstable angina, stable angina, acute myocardial infarction) from ICADs. In conclusion, this study reported a distinct miR-196a expression pattern in PBMCs of all patient groups and recommended a biomarker potential for miR-196a in discriminating ICADs from CADs or healthy controls. [ABSTRACT FROM AUTHOR]

Background: Diet-induced obesity can result in the development of a diverse spectrum of cardiovascular and metabolic diseases, including type 2 diabetes, dyslipidemia, non-alcoholic liver steatosis and atherosclerotic disease. MicroRNAs have been described to be important regulators of metabolism and disease development. Methods: In the current study, we investigated the effects of ubiquitous miR-100 overexpression on weight gain and the metabolic phenotype in a newly generated transgenic mouse strain under normal chow and high fat diet and used microarray expression analysis to identify new potential target genes of miR-100. Results: While transgenic overexpression of miR-100 did not significantly affect weight and metabolism under a normal diet, miR-100 overexpressing mice showed a reduced weight gain under a high fat diet compared to wildtype mice, despite an equal calorie intake. This was accompanied by less visceral and subcutaneous fat development and lover serum LDL cholesterol. In addition, transgenic miR-100 mice were more glucose tolerant and insulin sensitive and demonstrated increased energy expenditure under high fat diet feeding. A comprehensive gene expression profiling revealed the differential expression of several genes involved in lipid storage- and metabolism, among them CD36 and Cyp4A14. Our data showed a direct regulation of CD36 by miR-100, leading to a reduced fatty acid uptake in primary hepatocytes overexpressing miR-100 and the downregulation of several downstream mediators of lipid metabolism such as ACC1, FABP4, FAS and PPARγ in the liver. Conclusions: Our findings demonstrate a protective role of miR-100 in high fat diet induced metabolic syndrome and liver steatosis, partially mediated by the direct repression of CD36 and attenuation of hepatic lipid storage, implicating miR-100 as a possible therapeutic target in liver steatosis. [ABSTRACT FROM AUTHOR]

Background/Aims: Breast cancer (BC) is the most common cancer in women worldwide. Despite great advancements in cancer therapy in recent years, surgery and chemotherapy are still the mainstays of BC treatment. However, cancer cells usually develop mechanisms to evade cell death induced by chemotherapy. Thus, strategies are needed to reverse the chemoresistance of cancer cells. Methods: We established cisplatin-resistant BC models in MDA-MB-231 and MCF-7 BC cell lines through long-term exposure to cisplatin. Quantitative reverse transcription PCR was used to examine the expression of microRNA (miR)-100. MTT cell viability assays were performed to determine cell viability. Regulation of hematopoietic cell-specific protein 1-associated protein X-l (HAX-1) targeted by miR-100 was confirmed by western blotting and luciferase reporter assays. The mitochondrial membrane potential and apoptosis were measured by flow cytometry. Release of cytochrome c from the mitochondria into the cytoplasm, HAX-1 expression, and activation of caspase-9 and caspase-3 were detected by western blotting. Results: A clear decrease in miR-100 expression was observed in cisplatin-resistant MDA-MB-231 and MCF-7 cells (MDA-MB-231/R and MCF-7/R). Overexpression of miR-100 increased the sensitivity of MDA-MB-231/R and MCF-7/R cells to cisplatin treatment and promoted cisplatin-induced mitochondrial apoptosis by targeting HAX-1 gene. Conclusions: MiR-100 targeted HAX-1 to increase the chemosensitivity of BC by mediating the mitochondrial apoptosis pathway.

: microRNAs are playing important roles in the diagnosis and prognosis of pediatric acute lymphoblastic leukemia (ALL). Expression levels of miR-100 and miR-210 were assessed in bone marrow aspirate of 85 pediatric ALL patients compared to 12 healthy control using quantitative real-time polymerase chain reaction. Data were correlated with relevant clinico-pathological features of the patients, response to treatment, disease-free survival (DFS), and overall survival (OS). miR-100 was significantly downregulated in ALL patients [median: 1.21, range: 0–434.3] compared to the control group [median: 8.41, range; 0–840.3, P = 0.035]. miR-210 was significantly upregulated in ALL patients [median: 6.34, range: 1.16–1088.7] compared to the control group [median: 2.57, range: 0.11–709.2, P = 0.025]. The sensitivity, specificity, and area under curve of miR-100 were (64.7%, 62.5%, and 0.642; respectively, P = 0.035) at a cut-off 2.6 and that of miR-210 were (60%, 58.3% and 0.650; respectively, P = 0.025) at a cut-off 3.5. miR-100 overexpression associated with shorter DFS and OS (P = 0.033 and 0.046; respectively). Patients with miR-100 lowexpression showed a significant incidence of late death (P = 0.024). There was no significant association between miR-210 expression and DFS, OS, incidence of early or late death. : miR-100 and miR-210 could be used as potential diagnostic markers for pediatric ALL. miR-100 is a useful prognostic and predictive biomarker for childhood ALL. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) at early stages can be misdiagnosed as an oral ulcer (OU) due to similar symptoms, such as chronic and indurated ulcer. LncRNA NCK1-AS1 has been characterized as a key player in cervical cancer, while its role in OSCC is unknown. Methods: All participants were selected at Jiangxi Province Tumor Hospital from December 2016 to December 2018. Expression levels of NCK1-AS1 and miR-100 in plasma from both OSCC and OU patients were measured by RT-qPCR. Diagnostic analysis was performed through ROC curve. Potential interactions between NCK1-AS1 and miR-100 were detected by cell transfection experiments. Cell invasion and migration were assessed by Transwell assays. Results: The expression of NCK1-AS1 was upregulated in early-stage OSCC patients but not in OU patients. Upregulation of NCK1-AS1 distinguished OSCC patients from OU patients. The expression of miR-100 was inversely correlated with the expression of NCK1-AS1. Overexpression of NCK1-AS1 was followed by promoted OSCC cell invasion and migration. Overexpression of miR-100 did not affect the expression of NCK1-AS1 but inhibited the role of NCK1-AS1. Conclusions: Therefore, NCK1-AS1 may promote the metastasis of OSCC by downregulating miR-100. [ABSTRACT FROM AUTHOR]

Background: Non‐small cell lung cancer (NSCLC) is a leading subtype in lung cancer, with high morbidities and mortalities worldwide. microRNA (miRNA) has appeared to play indispensable roles in a variety of solid carcinomas. The current study focused on the functions of miR‐100 in NSCLC. Methods: qRT‐PCR was performed to detect miR‐100 and HOXA1 expressions in NSCLC tissues and cells. MTT and transwell assays were used to determine the functions of miR‐100 in NSCLC cell proliferation, invasion and migration abilities. Western blot was used to measure related protein expressions. Results: qRT‐PCR results showed that miR‐100 expressions were dramatically decreased in NSCLC tissues. MTT assays indicated that miR‐100 restoration inhibited NSCLC cell proliferation. Furthermore, transwell assay was performed to determine the impacts of miR‐100 on NSCLC invasion and migration abilities. As expected, the invasion and migration capacities were significantly repressed. Direct interactions between HOXA1 and miR‐100 were also verified via dual‐luciferase reporter assays. Western blot analysis demonstrated that miR‐100 exerted suppressive functions via regulating EMT and Wnt/β‐catenin in NSCLC cells. Conclusions: Our results showed that miR‐100 served antitumor roles in NSCLC, providing new evidence of miR‐100 as a promising therapeutic biomarker in NSCLC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the expression of circ_0072309 in patients with ischemic stroke (IS) and in LIFR humanized mice with middle cerebral artery occlusion (MCAO). Further, we explored the underlying mechanism of circ-0072309 in IS. MATERIALS AND METHODS: The content of circ-0072309 in serum of patients with IS (n = 70) was measured by qRT-PCR, and the ROC curve was analyzed. LIFR humanized mice were used to measure the content of circ-0072309 in ischemic hemisphere by qRT-PCR and the protein expression of cleaved-caspase-3, cleavedcaspase- 8 were detected by Western blot. After that, the expression of miR-100 in serum of patients with IS and in ischemic hemisphere of MCAO mice were detected, and then, we analyzed the correlation between the expression of circ-0072309 and miR-100. The binding sites between circ-0072309 and miR-100 were predicted by online database. We detected whether cric-0072309 bind to miR-100 by Dual-Luciferase report in bEnd2. In addition, bEnd2 was treated with oxygen-glucose deprivation (OGD) to simulate injury of cerebral vascular after cerebral ischemia. After treated with miR-100 mimic or miR-100-inhibitor, we detected the cell survival and rate of cell apoptosis, and the content of cleaved-caspase-3 and caspase-8 protein. The target mRNA of miR-100 was predicted by bioinformatics analysis and analyzed by Dual-Luciferase. After treating bEnd2 with circ-0072309 and miR-100 mimic, we analyzed the cell survival and apoptosis to identify the potential regulatory mechanism. RESULTS: The results of qRT-PCR showed that the expression of circ-0072309 was significantly decreased while the content of miR- 100 was significantly increased in the serum of IS patients and in the ischemic hemisphere of MCAO mice. There was a negative correlation between the expression of circ-0072309 and miR- 100. The results of Dual-Luciferase showed that circ-0072309 could directly bind to miR-100. After treating bEnd2 with OGD, miR-100-mimic caused a decrease rate of cell survival and an increased rate of apoptosis. Dual-Luciferase showed that miR-100 regulated cell survival and apoptosis by directly binding to mTOR. By comparing treated bEnd2 with circ-0072309, co-transfected bEnd2 with circ-0072309 and miR-100 reduced cell survival and increased apoptosis. CONCLUSIONS: According to these results, this study revealed that the circ_0072309-miR- 100-mTOR regulatory axis could alleviate IS, and it may be a potential target for the treatment of IS. [ABSTRACT FROM AUTHOR]

Objectives: Microvesicles (MVs) derived from human Wharton's jelly mesenchymal stem cells (MSC-MVs) were demonstrated to ameliorate acute lung injury (ALI). We have previously found that MSC-MV-transferred hepatocyte growth factor was partly involved in their therapeutic effects. Since MSC-MVs also contained a substantial quantity of miR-100, which plays an important role in lung cancer and injury, we speculated that miR-100 might similarly account for a part of the therapeutic effects of MSC-MVs. Methods: MSCs were transfected with miR-100 inhibitor to downregulate miR-100 in MSC-MVs. A rat model of ALI and cell injury in rat type II alveolar epithelial cell line (L2) was induced by bleomycin (BLM). A co-culture model of alveolar epithelial cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs and mechanism. Results: MSC-MV treatment attenuated BLM-induced apoptosis and inflammation in BLM-treated L2 cells and ameliorated BLM-induced lung apoptosis, inflammation, and fibrosis in BLM-induced ALI rats. The beneficial effect of MSC-MVs was partly eliminated when miR-100 was knocked down in MSCs. Moreover, MSC-MV-transferred miR-100 mediated the therapeutic effect of MSC-MVs in ALI through enhancing autophagy by targeting mTOR. Conclusion: MSC-MVs enhance autophagy and ameliorate ALI partially via delivery of miR-100. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is the most common pediatric malignancy and a major cause of morbidity and mortality in children. miR-100 is associated with progression of various diseases including AML. The aim of this study was to explore the underlying molecule mechanisms of miR-100 involved in AML. The expressions of miR-100 and ataxia telangiectasia mutated (ATM) in pediatric AML patients and cell lines were monitored using qRT-PCR and western blot assays. MTT assay was carried to evaluate cell viability. Cell apoptosis was measured by flow cytometry. The binding sites between miR-100 and ATM were predicted by mirtarbase database. Luciferase reporter assay was used to confirm the relationship between miR-100 and ATM. miR-100 expression was highly expressed in bone marrow of AML patients and cell lines. Moreover, Knockdown of miR-100 led to the inhibition of viability and promotion of apoptosis in Kasumi-1 and MV-4-11 cells. miR-100 harbored the 3′UTR of ATM. Meanwhile, the expression of ATM was downregulated in bone marrow of AML patients and AML cell lines. Subsequently, a negative correlation between miR-100 and ATM in bone marrow of AML patients was also observed. Furthermore, ectopic expression of ATM repressed cell viability while enhanced apoptosis. Notably, loss of ATM attenuated the effect of miR-100 depletion on cell viability and apoptosis in AML cells. miR-100 participates in cell viability and apoptosis by targeting ATM in pediatric AML. • miR-100 expression is Significantly elevated in bone marrow of pediatric AML patients and AML cell lines. • miR-100 depletion inhibits cell viability and induces cell apoptosis. • ATM is a direct target of miR-100. • ATM overexpression suppresses cell viability and induces cell apoptosis. • miR-100 regulates AML cell viability and apoptosis by inhibiting ATM. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence indicates that the dysregulation of miRNAs plays a vital role in tumorigenesis and progression of nasopharyngeal carcinoma (NPC). Thus, it is necessary to further investigate the function and mechanism of miRNAs in NPC. Methods: miR-100 expression was analyzed using publicly available databases and then tested using quantitative RT-PCR in NPC tissues and cell lines. MTT and colony formation assays and xenograft tumor model were used to test the NPC cell growth and proliferation abilities while modulating miR-100 expression. The target of miR-100 was predicted with TargetScan and validated with luciferase reporter assay, quantitative RT-PCR, and Western blot. Results: The expression of miR-100 was significantly reduced in NPC tissues and cell lines. Overexpression of miR-100 obviously suppressed NPC cell growth and proliferation, whereas silencing miR-100 promoted NPC cell growth and proliferation in vitro. HOXA1 (homeobox A1) was validated as a direct target of miR-100, and restoring HOXA1 expression could reverse the inhibitive effect of miR-100 on NPC cell growth and proliferation. The mRNA and protein expression of HOXA1 was increased in NPC cell lines. Furthermore, ectopic expression of miR-100 inhibited xenograft tumor growth in vivo. Conclusion: Taken together, our findings suggest that miR-100 could suppress NPC growth and proliferation through targeting HOXA1, providing a novel target for the miRNA-mediated therapy for patients with NPC in the future. [ABSTRACT FROM AUTHOR]

Aims: To explore the roles and regulatory mechanisms of the circular RNA (circRNA)-hsa-circ-0072309 in CAKI-1 and ACHN cells. Methods: CAKI-1 and ACHN cells were transfected with hsa-circ-0072309 overproduction vector (circRNA) and microRNA-100 (miR-100) mimic or the corresponding controls. Cell viability was detected with the CCK-8. The protein expression levels of p53, c-Myc, cleaved-caspase-3/9, matrix metalloproteinase (MMP)-2/9, vimentin, AKT, PI3K and mTOR were individually determined through western blot. qRT-PCR was used to examine the expressions of hsa-circ-0072309 and miR-100. The apoptotic rate and the migration or invasion rates were separately determined by the annexin v-FITC/PI with a flow cytometer and modified two-chamber migration assay or millicell hanging cell culture. Results: The hsa-circ-0072309 was poorly expressed in tumor tissue. Abundant hsa-circ-0072309 induced the inhibitions of cell proliferation, migration and invasion, as well as the PI3K/AKT and the mTOR cascades but enhancement of apoptosis. circRNA stimulated the down-regulation of miR-100, which was low-expressed in tumour tissue and whose overproduction abolished the impacts of circRNA on these elements mentioned above. Conclusion: The hsa-circ-0072309 played anti-tumour roles by targeting miR-100 by blocking the PI3K/AKT and mTOR cascades in the CAKI-1 and ACHN cell lines. [ABSTRACT FROM AUTHOR]

This research planned to grab the expression and impact of lncRNA HAGLROS in the biology and progression of mantle cell lymphoma. HAGLROS level in mantle cell lymphoma cell lines was detected, followed by investigation of the influences of HAGLROS silencing on Mino cell biological performances. Afterwards, the express patterns of HAGLROS vs. miR-100, as well as miR-100 vs. ATG5, were investigated. Furthermore, whether HAGLROS could regulate the signals of PI3K/AKT/mTOR was analyzed. HAGLROS level was high in mantle cell lymphoma cell lines. Silencing of HAGLROS inhibited Mino cell viability, increased apoptosis and decreased autophagy by sponging miR-100. Moreover, miR-100 targeted ATG5 fixed. Furthermore, HAGLROS suppression resulted in inhibition on the briskness of PI3K/AKT/mTOR signals. Concurrently HAGLROS suppression and miR-100 inhibitor markedly changed the impacts of HAGLROS down-regulation alone on activating PI3K/AKT/mTOR signals, which could further change after co-transfection of si-HAGLROS + miR-100 inhibitor + siATG5. Our findings point out that expression of HAGLROS is increased in mantle cell lymphoma cells and may function as an oncogene in mantle cell lymphoma. HAGLROS may promote tumour development by regulating miR-100/ATG5/PI3K/AKT/mTOR axis. [ABSTRACT FROM AUTHOR]

We planned to dig the significant role of long noncoding RNA HAGLROS in nasopharyngeal carcinoma (NPC) and the latent mechanism. The levels of HAGLROS in NPC tissues and cells were determined, followed by correlation analysis of HAGLROS level and clinicopathological features of patients suffered with NPC. The impacts of HAGLROS dysregulation on NPC cell viability, apoptosis, and the expression of apoptotic proteins and autophagy-related symbols were investigated. Moreover, we explored whether HAGLROS modulated the expression of autophagy-related gene 14 (ATG14) by competitively sponging miR-100, and then regulated the briskness of PI3K/AKT/mTOR signals in NPC development. HAGLROS level in NPC tissues and cell was very high. High level of HAGLROS indicated a short overall survival in NPC patients. Depressing of HAGLROS lessened NPC cell viability, enhanced apoptosis and reduced autophagy. Besides, HAGLROS negative controlled miR-100 and consequently targeted ATG14 expression, thus modulating NPC cell viability, apoptosis, and autophagy. Besides, dysregulation of HAGLROS/miR-100/ATG14 axis was correlated to the briskness of PI3K/AKT/mTOR signals in NPC cells. Our results indicate that of the augment of HAGLROS contributes to NPC development via modulating miR-100/ATG14 axis-mediated PI3K/AKT/mTOR signals. Our study will offer a comprehensive basis for better illustrating the pathogenesis of NPC. HAGLROS expression was upregulated in NPC tissues and cells. High expression of HAGLROS indicated a short overall survival in NPC patients. Silencing of HAGLROS promoted apoptosis and inhibited autophagy of NPC cells. HAGLROS regulated ATG14 expression in NPC cells via sponging miR-100. HAGLROS/miR-100/ATG14 axis regulated NPC development via PI3K/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common age-related neurodegenerative disease resulted from the progressive degeneration of dopaminergic neurons in the pars compacta region of substantia nigra. The goal of this study was to investigate the effects and mechanisms of long noncoding RNA (lncRNA) HAGLROS on the apoptosis and autophagy in PD. The MPTP-induced PD mouse model and MPP+-intoxicated SH-SY5Y cell model were established, and the expression levels of HAGLROS and miR-100 were determined. Subsequently, the effects of suppression of HAGLROS on apoptosis and autophagy in MPTP-induced PD mouse model and in MPP+-intoxicated SH-SY5Y cells were investigated. In addition, the association between HAGLROS and miR-100 as well as HAGLROS and activation of phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in MPP+-intoxicated SH-SY5Y cells was explored. HAGLROS was increasingly expressed in MPTP-induced PD mouse model and MPP+-intoxicated SH-SY5Y cells and suppression of HAGLRO decreased apoptosis and autophagy in both in vivo and in vitro PD models. Further in vitro studies showed that HAGLRO negatively regulated miR-100 expression, and HAGLROS regulated apoptosis and autophagy of MPP+-intoxicated SH-SY5Y cells through sponging miR-100. Moreover, ATG10 was identified as a target of miR-100. Besides, suppression of HAGLROS alleviated MPP+-intoxicated SH-SY5Y cell injury by activating PI3K/AKT/mTOR pathway. Our findings reveal that upregulation of HAGLROS may contribute to the development of PD via inhibiting apoptosis and autophagy, which may be achieved by regulating miR-100/ATG10 axis and PI3K/AKT/mTOR pathway activation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aims to ascertain the effect of miR-100 on inflammation, apoptosis and functional rehabilitation after spinal cord injury (SCI) and the potential mechanism. MATERIALS AND METHODS: Firstly, microglia were extracted from 3-day-old neonatal rats and cultured for the purpose of inflammatory activation. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to detect the levels of miR-100, toll-like receptors 4 (TLR4) and nuclear factor-κB (NF-κB). Moreover, proteins expressions of I-κB and induced-nitric oxide synthase (iNOS) and apoptosis-related genes were measured by Western blotting. In addition, SCI model was established in rats. Expressions of inflammatory factors in SCI rats were determined by enzyme-linked immunosorbent assay (ELISA) assay. Expression levels of TLR4/NF-κB pathway and miR-100 were determined by qRT-PCR. Immunofluorescence was conducted to measure activated microglia. Hindlimbs motor function in SCI rats was estimated via BBB 21-point rating scale. RESULTS: In activated microglia, miR-100 level decreased, while TLR4 and NF-κB levels increased. The protein level of I-κB decreased and iNOS increased. Transfection of miR-100 mimics reversed the above trends. Inflammatory factors were highly elevated in SCI rats and mRNA levels of the TLR4/NF-κB pathway and miR-100 were down-regulated, which were ameliorated in SCI rats overexpressing miR-100 in vivo. The amount of activated microglia was declined with the administration of miR-100 mimics compared with the untreated SCI rats. Furthermore, apoptosis- related proteins were down-regulated by miR-100 mimics injection. Motor function in the miR-100 mimics group was improved better than that in the SCI group. CONCLUSIONS: MiR-100 alleviates inflammation of microglia and neuronal tissue apoptosis, and improves motor function following SCI via inhibiting the TLR4/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Purpose: To explore the clinical significance and mechanism of long noncoding RNA (lncRNA) HAGLROS in ovarian cancer.Methods: The expression of HAGLROS in ovarian cancer was verified by online databases and quantitative reverse transcription polymerase chain reaction (qRT-PCR), and its relationship with clinicopathological parameters was analysed. Pearson correlation analysis was used to study the correlation between HAGLROS and miR-100 in ovarian cancer. Meta-analysis was used to explore the expression of miR-100 in ovarian cancer. In addition, we used bioinformatics to explore the target genes of miR-100 and perform functional analysis.Results: HAGLROS was significantly upregulated in ovarian cancer (P < 0.001) and was closely related to disease stage (P = 0.033), tumour size (P = 0.032) and poor prognosis (P = 0.019). HAGLROS had a certain diagnostic value in ovarian cancer (area under the curve = 0.751). MiR-100 was negatively correlated with HAGLROS (r = 0.167, P = 0.001) and significantly downregulated in ovarian cancer. Bioinformatics analysis predicted a total of 31 potential target genes that interact with miR-100. These target genes were mainly involved in the regulation of cellular catabolic process, proteoglycan biosynthetic process and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Among them, mTOR and ZNRF2 are hub genes.Conclusion: HAGLROS is a potential biomarker for early diagnosis and prognosis evaluation of ovarian cancer. It can be used as a molecular sponge of miR-100 to regulate the expression of mTOR and ZNRF2 and affect the signal transduction of the mTOR pathway. HAGLROS is expected to be a new target for the treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Circulating microRNAs (miRNAs) have a vital role in Hepatitis B virus (HBV) diagnosis and therapeutics. miR-100 was reported to be associated with various aspects of HBV biology. This study focused on a miR-100 Single Nucleotide Polymorphism (SNP) (rs1834306 T/C) and its contribution to an individual's susceptibility and prognosis of HBV infection. The effect of SNP on miR-100 expression will be also evaluated. Two hundred subjects: 100 HBV infected patients and 100 age-and-sex-matched healthy individuals served as a control group. SNP detection was performed using polymerase chain reaction technique with sequence-specific primers (PCR-SSP) method and miR-100 expression through quantitative real-time PCR (qRT-PCR). Our result showed a significant up-regulation of miR-100 expression in HBV patients versus the control group (P <.01). A positive correlation was found between viral load and elevation in miR-100 expression (r = 0.508; P <.01). Concerning miR-100 expression in different genotypes/alleles, TC genotype and T allele in coincides with a significantly elevated expression level of miR-100 (P <.001) in HBV patients than in controls. Best of our knowledge, it is the first observational prospective case-control study concerned with miR-100 (rs1834306 T/C) SNP in the Egyptian population. However, the small size of this preliminary work required more prospective investigations to confirm our data. • An observational prospective case-control study focus on miR-100 on HBV patients. • A significant up-regulation of miR-100 expression in HBV patients was observed. • Significant increase of miR-100 was detected in patients harboring TC genotype/T allele. • Positive correlation was found between PCR value and increase of miR-100 expression. • miR-100 may be considered as a marker to appraise prognosis of patients with HBV. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is one of the most commonly diagnosed age-related bone diseases worldwide, and it is also one of the leading causes of fracture. MicroRNAs (miRNAs) are critical molecular regulators that are involved in the bone re-modelling processes, and the circulating miRNAs were stable in the peripheral blood. Thus, to detect the level of miRNAs in plasma of osteoporotic patients may be an efficient, repeatable, and inexpensive method for the early diagnosis and evaluation of the therapeutic efficacy of osteoporosis. The aim of the present study was to investigate the potential diagnostic value of miR-100 in plasma of patients with osteoporosis. Methods: A total of 120 osteoporotic patients were recruited and 120 healthy individuals were also included as the control group. The plasma of the participants was collected and the RNAs were extracted. The expressions of miR-100 in different clinical samples were examined using the RT-qPCR method. Furthermore, receiver operating characteristics curve (ROC) was drawn to determine the diagnostic value of miR-100 for osteoporosis. Next, the correlation between the plasma levels of miR-100 and T-scores of the patients were evaluated and, finally, the correlation between the plasma level of miR-100 and the expression levels of 25OH-D2 and 25OH-D3 were analyzed. Results: miR-100 was significantly increased in plasma of patients with osteoporosis in comparison with healthy individuals; moreover, results of ROC analysis indicated that plasma level of miR-100 is a sensitive biomarker that could distinguish osteoporosis patients from healthy controls (AUC, 0.8916, 95% confidence interval (CI), 0.8468 to 0.9364). Furthermore, miR-100 was found to be negatively correlated with both vBMD (r = -0.3117, p = 0.0005) and Lumbar Spine L2-L4 T-score in patients with osteoporosis (r = -0.2929, p = 0.012). Finally, the plasma level of miR-100 was negatively correlated with the levels of 25OH-D2 (r = -0.3002, p = 0.0008) and 25OH-D3 (r = -0.3105, p = 0.0006) of the osteoporotic patients. Conclusions: miR-100 was abnormally increased in the plasma of osteoporotic patients, suggesting that circulating miR-100 could serve as potential biomarker for the diagnosis and treatment osteoporosis. [ABSTRACT FROM AUTHOR]

The expression of microRNA (miR)-100 in non-small cell lung cancer (NSCLC) and its association with clinicopathological features and poor prognosis were investigated. A total of 283 patients with NSCLC were enrolled in The First Hospital of Jiaxing from February 2013 to April 2015. Total RNA was extracted from cancer tissues and corresponding adjacent normal tissues. The expression of miR-100 was detected by RT-qPCR. Association between the expression level of miR-100 with clinicopathological features and prognosis of NSCLC were analyzed. The expression level of miR-100 in NSCLC tissues was lower than that in the normal tissues (P<0.05). According to the median expression level of miR-100 in cancer tissue, patients were divided into the high expression and low expression groups. Cross-tabulation analysis showed that the expression level of miR-100 was significantly associated with patients' age, TNM stage, metastasis and histological type (P<0.05), but not with sex (P>0.05). The proportion of patients with low miR-100 expression was higher in patients who died than in those who survived (P<0.05). Univariate prognostic analysis showed that miR-100 expression, age, TNM staging, and metastasis may be risk factors for poor prognosis in patients with NSCLC. Cox multivariate regression analysis showed that the downregulated miR-100 expression, advanced TNM stage, and metastasis were independent risk factors for poor prognosis of NSCLC. The relatively low expression level of miR-100 in NSCLC is associated with poor prognosis of patients. Therefore, miR-100 shows potential as a prognostic marker for NSCLC. [ABSTRACT FROM AUTHOR]

We identified that transforming growth factor-β (TGF-β) induces long non-coding RNA (lncRNA) MIR100HG along with its host microRNAs (miRNAs) miR-100 and miR-125b, to regulate its response in pancreatic ductal adenocarcinoma (PDAC). Importantly let-7a, despite originating from MIR100HG, remains unchanged because post-transcriptionally repressed by lin-28 homolog B (LIN28B). A novel method for global miRNA-target discovery identified that miR-100/125b regulates crucial PDAC pathways.

MicroRNAs (miRNAs) are a recently discovered class of endogenous, small (about 22 nucleotides) non-coding RNAs, which play important roles in cancer development and progression. Emerging evidence shows that microRNAs exert their regulatory effects by directly binding to the 3'- untranslated regions (UTRs) of their target genes. MicroRNA-100 (miR-100) is aberrantly expressed and functions in many human cancers by regulating multiple cell processes, such as cell cycle, proliferation, differentiation, migration, invasion and apoptosis, via post-transcriptionally regulating various target genes. A better understanding of the molecular mechanisms involved in miR-100-mediated tumor progression will provide an opportunity for exploring novel miR-100-based targeted therapies for human cancers. This review aims to summarize the recently published literature on the roles of miR-100 in regulating tumorigenesis, and explore its potential clinical applications for cancer diagnosis, prognosis and clinical treatment.

Background/Aims: The pathogenesis of lumbar disc degeneration (LDD) involved activation of matrix metalloproteinase 13 (MMP13) by differential expression of fibroblast growth factor receptor 1 (FGFR1) and FGFR3. Nevertheless, the molecular regulation of FGFR1 and FGFR3 in the lumber disc cells remains elusive. Methods: We examined the FGFR1 and FGFR3 levels and microRNAs (miRNAs) levels in the resected LDD discs, compared to the traumatized, non-LDD discs. We analyzed the binding of miR-100 to the 3′UTR of FGFR3 mRNA and its effects on FGFR3 translation by bioinformatics analysis and by luciferase-reporter assay, respectively. We modified miR-100 levels in a human nucleus pulposus SV40 cell line (HNPSV), and examined the effects on the expression of FGFR3 and MMP13, by RT-qPCR, Western blot and ELISA. Results: The levels of FGFR1 and miR-100 were significantly higher, while the levels of FGFR3 were significantly lower, in LDD discs, compared to the control non-LDD discs. The levels of FGFR3, but not the levels of FGFR1, inversely correlated with the levels of miR-100. Moreover, miR-100 was found to bind to the 3'UTR of FGFR3 mRNA to prevent its translation. In miR-100-modified HNPSV cells, we found that miR-100 decreased FGFR3 levels, and increased MMP13 levels. Conclusion: miR-100 may activate MMP13 through 3′UTR-suppressoin of FGFR3 mRNA to facilitate development of LDD.

Background: Neuroblastoma is a common malignant tumor stemming from the sympathetic nervous system in children, which is often life-threatening. The genetics of neuroblastoma remains unclear. Studies have shown that miRNAs participate in the regulation of a broad spectrum of biological pathways. The abnormity in the miRNA is associated with the risk of various cancers, including neuroblastoma. However, research on the relationship of miRNA polymorphisms with neuroblastoma susceptibility is still in the initial stage., Methods: In this research, a retrospective case-control study was conducted to explore whether miR-100 rs1834306 A > G polymorphism is associated with neuroblastoma susceptibility. We enrolled 402 cases and 473 controls for the study. The logistic regression analysis was adopted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between miR-100 rs1834306 A > G and neuroblastoma risk., Results: Our results elucidated that the miR-100 rs1834306 A > G polymorphism was associated with the decreased risk of neuroblastoma (AG versus AA: adjusted OR = 0.72, 95% CI = 0.53-0.98, and P = 0.038). The subsequent stratified analysis further found that rs1834306 AG/GG genotype reduced the risk of neuroblastoma in the subgroup with tumors of the mediastinum origin (adjusted OR = 0.63, 95% CI = 0.41-0.95, and P = 0.029)., Conclusions: In summary, miR-100 rs1834306 A > G polymorphism was shown to associate with decreased neuroblastoma risk in Chinese children, especially for neuroblastoma of mediastinum origin. This conclusion needs to be verified in additional large-size case-control studies., (© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

OBJECTIVE: Mammalian target of rapamycin (mTOR) can negatively regulate cell autophagy, while its expression and activity are associated with the pathogenesis of osteosarcoma. MicroRNA 100 (MiR-100) down-regulation is associated with the pathogenesis and chemo- sensitivity of osteosarcoma. Bioinformatics analysis revealed the targeted relationship between miR-100 and the 3'-UTR of mTOR. We investigate the role of miR-100 in affecting mTOR expression, osteosarcoma cell autophagy, and sensitivity to cisplatin. PATIENTS AND METHODS: MiR-100, mTOR, and Beclin-1 expressions in osteosarcoma tissue and normal control were compared. The relationship between miR-100 and mTOR was verified by dual luciferase assay. MiR-100, mTOR, and Beclin-1 levels in MG-63 cells and MG-63/ DDP cells were tested. Cell apoptosis was determined by using flow cytometry. Cell malignancy was evaluated by colony formation assay. RESULTS: MiR-100 and Beclin-1 significantly declined, while mTOR significantly increased in osteosarcoma tissue compared with that of normal tissue (p<0.05). MiR-100 targeting significantly inhibited mTOR expression compared to that of untreated (p<0.05). MiR-100 expression was down-regulated and mTOR level was elevated in MG-63/DDP cells compared with MG-63 cells (p<0.05). MG-63/DDP cells exhibited reduced cell autophagy and apoptosis, and enhanced colony formation induced by DDP. MiR-100 mimic and/or small interfere mTOR (simTOR) significantly promoted Beclin-1 expression, cell autophagy, and cell apoptosis, while attenuated colony formation. CONCLUSIONS: MiR-100 declined, while mTOR up-regulated in osteosarcoma tissue. MiR-100 up-regulation enhanced cell autophagy and apoptosis induced by cisplatin via targeted inhibiting of mTOR. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is one of the deadliest malignancies worldwide. Esophageal squamous cell carcinoma (ESCC) constitutes the most common type of EC in Asian countries. Despite advanced surgical techniques, 5-year survival of the affected patients is very low. Therefore, identification of genetic factors and cellular regulatory pathways, including microRNAs (miRNAs), in esophageal carcinogenesis is necessary for early detection. MiRNAs are a class of small non-coding RNA about 18-24 nucleotides in length that negatively regulate gene expression. Deregulation of miRNAs was shown to have a crucial role in the pathways underlying tumorigenesis and tumor progression. Evidence indicates that aberrant expression pattern of miR-100 is associated with pathogenesis of ESCC. The function and expression pattern of miR-100 in ESCC are controversial and its effects in tumor progression has not been fully elucidated. A better understanding of molecular procedures mediated by miR-100 in carcinogenesis, may lead to the opportunity of exploring potential miR-100 based therapeutic applications. In this review, we provide an overview of miR-100, including its important regulation pathways and target genes involved in the development of cancers, emphasizing on its potential role in ESCC. [ABSTRACT FROM AUTHOR]

Pneumonia is a lower respiratory disease caused by pathogens or other factors. This study aimed to explore the roles and mechanism of long noncoding RNA HAGLROS in lipopolysaccharides (LPS)-induced inflammatory injury in pneumonia. The HAGLROS expression in serum of patients with acute stage pneumonia was detected. To induce pulmonary injury, WI-38 human lung fibroblasts were stimulated with lipopolysaccharides (LPS). The HAGLROS expressions in LPS-treated WI-38 cells and the effects of HAGLROS knockdown on the viability, apoptosis, and autophagy of LPS-induced cells were detected. Moreover, the regulatory relationship between HAGLROS and miR-100 was explored as well as the functional targets of miR-100 were identified. Furthermore, the regulatory relationship between miR-100 and PI3K/AKT/NF-κB pathway was elucidated. LncRNA HAGLROS was higher expressed in serum of patients with acute stage pneumonia compared with that in serum of healthy control. LPS caused WI-38 cell injury and increased HAGLROS levels. Downregulation of HAGLROS alleviated LPS-induced cell injury via increasing cell viability, and inhibiting apoptosis and autophagy. Moreover, there was a negative correlation between HAGLROS and miR-100, and the effects of HAGLROS downregulation on LPS-induced apoptosis and autophagy in WI-38 cells were by regulation of miR-100. Furthermore, NFΚB3 was verified as a functional target of miR-100 and effects of miR-100 inhibition on LPS-induced WI-38 cell injury were alleviated by knockdown of NFΚB3. Besides, Knockdown of HAGLROS inhibited the activation of PI3K/AKT/NF-κB pathway. Our findings reveal that downregulation of HAGLROS may alleviate LPS-induced inflammatory injury in WI-38 cells via modulating miR-100/NF-κB axis. HAGLROS/miR-100/NF-κB axis may provide a new strategy for treating acute stage of pneumonia. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a cancer pattern that often develops in the epithelial cells of the nasopharynx. miR-100 is a miRNA that has been identified in a number of cancers. The aim of the present study was to investigate whether miR-100 can affect cell migration and proliferation of NPC by targeting insulin-like growth factor 1 receptor (IGF1R). Western blot analysis was used to determine the protein levels of genes. The reverse transcription-quantitative PCR (RT-qPCR) was used to detect the expression level of miR-100 and IGF1R. Transwell assay was used to detect the migration and invasion of cell lines. The luciferase reporter assay was employed to confirm the target gene of miR-100. miR-100 expression was highly reduced in NPC tissues compared with non-cancerous tissues. Overexpression of miR-100 significantly inhibited the migration and invasion of NPC cell lines C666-1 and SUNE1. IGF1R was a downstream target of miR-100 and was downregulated by miR-100. Knockdown of IGF1R by siRNA suppressed cell proliferation of the C666-1 cell line. The newly identified miR-100/IGF1R axis offers novel biomarkers for the therapeutic intervention of NPC treatment. As a result, our findings suggest that miR-100 plays an important role in suppressing migration and invasion of NPC cells and suppresses IGF1R expression by directly targeting its 3'-UTR. It is suggested that miR-100 may be a novel therapeutic target of microRNA-mediated suppression of cell migration and invasion in NPC. However, the role of the miR-100/IGF1R axis in NPC progression needs further investigation. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) regulate genes expression by directly binding to the 3′ untranslated region (3′UTR) of specific target mRNAs. Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) are proposed to be important in the development of breast cancer (BC). In the present study, we conducted a case-control study with 266 BCE patients and 288 control women to examine the possible association of miRNAs polymorphisms (miR-100 rs1834306, miR-124-1 rs531564, miR-218-2 rs11134527, miR-301b rs384262, miR-605 rs2043556, and miR-4293 rs12220909) with BC susceptibility. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The findings showed miR-218-2 rs11134527 variant increased the risk of BC (OR = 7.70, 95%CI = 3.84–15.43, P < .0001, GA vs GG and OR = 6.86, 95%CI = 3.47–13.57, P < .0001, A vs G). Regarding miR-301b rs384262 polymorphism, we observed that this variant significantly increased the risk of BC (OR = 3.12, 95%CI = 2.20–4.45, P < .0001, AG vs AA and OR = 2.22, 95%CI = 1.68–2.93, P < .0001, G vs A). Our findings did not support an association between miR-100 rs1834306, miR-124-1 rs531564, miR-605 rs2043556 and miR-4293 rs12220909 polymorphism and the risk of BC. In conclusion, the finding showed that miR-218-2 rs11134527 and miR-301b rs384262 variant might contribute to increase the risk of BC in a sample of Iranian population. Additional studies with larger sample sizes and different ethnicities are necessary to confirm our finding. [ABSTRACT FROM AUTHOR]

Micro RNAs (mi RNAs) are small RNA molecules that regulate gene expression associated with many complex biological processes. By comparing mi RNA expression between long-lived cohorts of Drosophila melanogaster that were fed a low-nutrient diet with normal-lived control animals fed a high-nutrient diet, we identified miR-184, let-7, miR-125, and miR-100 as candidate mi RNAs involved in modulating aging. We found that ubiquitous, adult-specific overexpression of these individual mi RNAs led to significant changes in fat metabolism and/or lifespan. Most impressively, adult-specific overexpression of let-7 in female nervous tissue increased median fly lifespan by ~22%. We provide evidence that this lifespan extension is not due to alterations in nutrient intake or to decreased insulin signaling. [ABSTRACT FROM AUTHOR]

Chronic arsenic treatment induces epithelial-mesenchymal transition (EMT) and promotes tumorigenicity, but the mechanism is unclear. MiR-100 has been shown to be involved in this biologic process. In this study, we hypothesize that inactivation of miR-100 combined with low concentration of arsenic exposure could promote the malignant transformation of human bronchial epithelial cells (BEAS-2B cell) by promoting EMT. To test this hypothesis, BEAS–2B cells were treated with low-dose of As2O3chronically, and lentiviral vectors were used to mediate the inhibition of miR-100 expression. Flow cytometry, cloning formation, and transwell assays were used to examine cell cycle progression, cell proliferation, and cell migration, respectively. The mouse xenograft model was used to investigate the cell malignant growth in vivo, and western blot was used to detect EMT related marker expressions. Our results showed that, the inactivation of miR-100 combined with arsenic treatment significantly promoted the proliferation, viability, and migration of BEAS-2B cells in vitro, and tumorigenesis in vivo. Consistently, the EMT related marker expressions were also significantly increased in corresponding groups. Our data indicate that inactivation of miR-100 combined with chronic arsenic treatment promotes tumorigenicity of BEAS-2B cells via activation of EMT. This novel insight may help us to better understand the pathogenesis of arsenic carcinogenesis. [ABSTRACT FROM PUBLISHER]

Purpose: Medulloblastoma (MB) is the most common malignant tumor of the central nervous system (CNS) in children. Despite its relative good survival rates, treatment can cause long time sequels and may impair patients' lifespan and quality, making the search for new treatment options still necessary. Polo like kinases (PLKs) constitute a five-member serine/threonine kinases family (PLK 1-5) that regulates different stages during cell cycle. Abnormal PLKs expression has been observed in several cancer types, including MB. As gene regulators, miRNAs have also been described with variable expression in cancer. Methods: We evaluated gene expression profiles of all PLK family members and related miRNAs (miR-100, miR-126, miR-219, and miR-593*) in MB cell lines and tumor samples. Results: RT-qPCR analysis revealed increased levels of PLK1-4 in all cell lines and in most MB samples, while PLK5 was found underexpressed. In parallel, miR-100 was also found upregulated while miR-129, miR-216, and miR-593* were decreased in MB cell lines. Variable miRNAs expression patterns were observed in MB samples. However, a correlation between miR-100 and PLK4 expression was observed, and associations between miR-100, miR-126, and miR-219 expression and overall and event free survival were also evinced in our cohort. Moreover, despite the lack of association with clinico-pathological features, when comparing primary tumors to those relapsed, we found a consistent decrease on PLK2, miR-219, and miR-598* and an increase on miR-100 and miR-126. Conclusion: Specific dysregulation on PLKs and associated miRNAs may be important in MB and can be used to predict prognosis. Although miRNAs sequences are fundamental to predict its target, the cell type may also be consider once that mRNA repertoire can define different roles for specific miRNA in a given cell. [ABSTRACT FROM AUTHOR]

A majority of early colorectal cancers ( CRCs) with submucosal invasion undergo surgical operation, despite a very low incidence of lymph node metastasis. Our study aimed to identify micro RNAs (mi RNAs) specifically responsible for lymph node metastasis in submucosal CRCs. Micro RNA microarray analysis revealed that miR-100 and miR-125b expression levels were significantly lower in CRC tissues with lymph node metastases than in those without metastases. These results were validated by quantitative real-time PCR in a larger set of clinical samples. The transfection of a miR-100 or miR-125b inhibitor into colon cancer HCT116 cells significantly increased cell invasion, migration, and MMP activity. Conversely, overexpression of miR-100 or miR-125b mimics significantly attenuated all these activities but did not affect cell growth. To identify target m RNAs, we undertook a gene expression array analysis of miR-100-silenced HCT116 cells as well as negative control cells. The Ingenuity Pathway Analysis, TargetScan software analyses, and subsequent verification of m RNA expression by real-time PCR identified mammalian target of rapamycin (m TOR) and insulin-like growth factor 1 receptor ( IGF1R) as direct, and Fas and X-linked inhibitor-of-apoptosis protein ( XIAP) as indirect candidate targets for miR-100 involved in lymph node metastasis. Knockdown of each gene by si RNA significantly reduced the invasiveness of HCT116 cells. These data clearly show that downregulation of miR-100 and miR-125b is closely associated with lymph node metastasis in submucosal CRC through enhancement of invasion, motility, and MMP activity. In particular, miR-100 may promote metastasis by upregulating m TOR, IGF1R, Fas, and XIAP as targets. Thus, miR-100 and miR-125b may be novel biomarkers for lymph node metastasis of early CRCs with submucosal invasion. [ABSTRACT FROM AUTHOR]

OBJECTIVE: MicroRNAs are noncoding RNA molecules involved in the development and progression of tumors. We have found that miRNA-100 is underexpressed in metastatic prostate cancer compared to localized disease. Conversely higher levels of miR-100 are related to biochemical recurrence after surgery. This suggests that miR-100 may be a context-dependent miRNA, acting as oncogene or tumor suppressor miRNA. Our aim is to demonstrate the role of miR-100 in the control of predicted target genes in prostate cancer cell lines. METHODS: Cell lines DU145 and PC3 were transfected with miR-100, antimiR-100 and after 24 h and 48 h of exposure, qRT-PCR and western blot were performed for mTOR, FGFR3, THAP2, SMARCA5 and BAZ2A. RESULTS: There was reduction in mTOR (p = 0.025), THAP2 (p = 0.038), SMARCA5 (p = 0.001) and BAZ2A (p = 0.006) mRNA expression in DU145 cells after exposure to miR-100. In PC3 cells, mTOR expression was decreased by miR-100 (p = 0.01). There was a reduction in the expression levels of proteins encoded by studied genes, ranging from 34% to 69%. CONCLUSIONS: We demonstrate that miR-100 is a context-dependent miRNA controlling BAZ2, mTOR, FGFR3, SMARCA5 and THAP2 that might be involved in PC progression. The elucidation of the roles of miRNAs in tumors is important because they can be used as therapeutic targets in the future.

Short-term (5-10 days) calorie restriction (CR) downregulates muscle protein synthesis, with consumption of a high protein-based diet attenuating this decline. Benefit of increase protein intake is believed to be due to maintenance of amino acid-mediated anabolic signaling through the mechanistic target of rapamycin complex 1 (mTORC1), however, there is limited evidence to support this contention. The purpose of this investigation was to determine the effects of prolonged CR and high protein diets on skeletal muscle mTORC1 signaling and expression of associated microRNA (miR). 12-wk old male Sprague Dawley rats consumed ad libitum (AL) or calorie restricted (CR; 40%) adequate (10%, AIN-93M) or high (32%) protein milk-based diets for 16 weeks. Body composition was determined using dual energy X-ray absorptiometry and muscle protein content was calculated from muscle homogenate protein concentrations expressed relative to fat-free mass to estimate protein content. Western blot and RT-qPCR were used to determine mTORC1 signaling and mRNA and miR expression in fasted mixed gastrocnemius. Independent of dietary protein intake, muscle protein content was 38% lower (P < 0.05) in CR compared to AL. Phosphorylation and total Akt, mTOR, rpS6 and p70S6K were lower (P < 0.05) in CR versus AL, and total rpS6 was associated with muscle protein content (r = 0.64, r2 = 0.36). Skeletal muscle miR expression was not altered by either energy or protein intake. This study provides evidence that chronic CR attenuates muscle protein content by downregulating mTORC1 signaling. This response is independent of skeletal muscle miR and dietary protein.

摘 要： 【目的】 在宫颈癌Ｈｅｌａ、Ｓｉｈａ细胞中上调ｍｉＲ－１００后，研究细胞侵袭及迁移功能及顺铂耐药性变化并探讨其机制。【方法】 将ｍｉＲ－１００ ｍｉｍｉｃ通过ｌｉｐｏｍａｘ试剂转染至宫颈癌细胞Ｈｅｌａ、Ｓｉｈａ中，细胞主要分为两组：ＮＣ组，为空白对照；ｍｉｒ１００组，为上调ｍｉＲ－１００后的细胞。ｔｒａｎｓｗｅｌｌ法观察细胞侵袭性，划痕实验观察迁移性；ＷＢ测定上皮间质变相关蛋白Ｅ－Ｃａｄｈｅｒｉｎ、Ｓｎａｉｌ、Ｖｉｍｉｎｔｉｎ及ＭＭＰ２、ｕＰＡ的表达；ＣＣＫ８法测定顺铂耐药性。 【结果】 ①两系宫颈癌细胞上调ｍｉＲ－１００后，细胞的侵袭、迁移性降低；②上调ｍｉＲ－１００后的宫颈癌细胞中上皮相关分子Ｅ－Ｃａｄｈｅｒｉｎ表达上调，间质表型分子Ｓｎａｉｌ、Ｖｉｍｉｎｔｉｎ表达下调，ＭＭＰ－２表达无差异，ｕＰＡ表达下降；③不同浓度顺铂作用（Ｐ ＜ ０．００１）及是否转染ｍｉｒ－１００ ｓｉＲＮＡ（Ｐ ＜ ０．００１）对细胞存活率的改变均具有显著统计学意义，且浓度因素与处理因素间相对独立；在Ｓｉｈａ细胞中得出相同结论（Ｐ ＜ ０．００１）。ＨｅｌａＮＣ、Ｈｅｌａ １００细胞株顺铂ＩＣ５０（μｍｏｌ／Ｌ）分别为：８．１９ ± ０．３４、５．３８ ± ０．４７，ＳｉｈａＮＣ、Ｓｉｈａ １００的ＩＣ５０分别为８．８６ ± ０．９２、６．１９ ± ０．２３， Ｐ ＜ ０．０５。【结论】 ｍｉＲ－１００在宫颈癌细胞Ｈｅｌａ及Ｓｉｈａ中通过降低上皮间质变过程起抑制侵袭和转移的作用，该功能可能与ｕＰＡ的改变有关。上调ｍｉＲ－１００可降低宫颈癌细胞对顺铂的耐药性。

Non-coding RNAs (ncRNAs) play a vital role in the diagnosis and treatment of hepatitis B virus (HBV). ncRNAs include major classes, such as microRNAs (miRNAs/miRs) and long ncRNAs (lncRNAs). The present study focused on miR-100 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) single nucleotide polymorphisms (SNPs) and their expression levels. In addition to their dual effect on susceptibility to hepatitis B virus (HBV) infection, new molecular biomarkers of HBV infection are suggested. In the present study, 100 patients with HBV infection vs. 100 healthy controls were enrolled. miR-100 SNP (rs1834306T/C) was detected using the polymerase chain reaction sequence-specific primers technique, while MALAT1 SNP (rs619586A/G) was detected using the restriction fragment length polymorphism-PCR technique. Their expression levels were measured using reverse transcription-quantitative PCR. As per the miR-100 genotyping results, the TC genotype represented the most frequent genotype in all subjects. However, in MALAT1 SNP, only the dominant AA genotype was detected. A significant upregulation of both miR-100 (P<0.01) and MALAT1 (P<0.05) expression was observed in the patient group compared to the controls. A positive correlation was found between the viral load and an elevation in miR-100 and MALAT1 expression levels (r=0.508, P<0.01; and r=0.282, P<0.05, respectively). On the whole, the present study demonstrates that miR-100 and MALAT1 may be considered as potential molecular markers for the prognosis of patients with HBV infection. To the best of our knowledge, this is the first observational prospective case-control study to scrutinize all the possible correlations between miR-100 (rs1834306T/C) and MALAT1 (rs619586A/SNPs) and their expression levels. Further extensive studies with large sample sizes are recommended to confirm the findings obtained herein. [ABSTRACT FROM AUTHOR]