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Background: Glioma is the most common malignant brain tumor. GPR133 is a key factor in the progression of glioma. However, the role of GPR133 in glioma invasion and EMT and the microRNAs (miRNAs) associated with this pathway are still poorly understood.Objective: This study aims to elucidate the biological function of miR-106a-5p and GPR133 in glioma as well as the molecular mechanism of their interaction.Methods: The mRNA expression of miR-106a-5p and GPR133 in glioma specimens and cells was analyzed by quantitative real-time polymerase chain reaction (qRT–PCR). The protein level of GPR133 and the levels of invasion- and EMT-related proteins were measured by western blotting. miR-106a-5p and GPR133 function in glioma cells was determined through cell counting kit-8 (CCK-8), transwell, wound healing, colony formation assays in vitro and xenograft assays in vivo. To determine the targeting relationship between miR-106a-5p and GPR133, a dual-luciferase reporter assay was conducted.Results: A marked reduction in miR-106a-5p expression was observed in glioma cells and specimens. Patients with high expression of miR-106a-5p had a good prognosis, while patients with high expression of GPR133 had a shorter OS. Additionally, overexpression of miR-106a-5p or downregulation of GPR133 inhibited the progression of glioma cells. Furthermore, miR-106a-5p negatively regulated GPR133 expression by binding to its 3′-UTR, and restrained the invasion, migration, proliferation and EMT of glioma cells by targeting GPR133.Conclusions: miR-106a-5p is a tumor suppressor that negatively regulates GPR133. The miR-106a-5p/GPR133 axis could potentially serve as a therapeutic target for glioma. [ABSTRACT FROM AUTHOR]

Abstract Background It is essential to find reliable biomarkers for early diagnosis and prognosis of acute heart failure (AHF) for its mitigation. Currently, increasing attention is paid to the role of microRNAs (miRNAs/miRs) as diagnostic or prognostic markers for cardiovascular diseases. Since plasma miR-106a-5p has been observed to be downregulated in AHF, its value in the diagnosis and prognostic assessment of AHF deserves further exploration. Accordingly, this study analyzed the diagnostic and prognostic value of plasma miR-106a-5p in AHF patients. Methods Prospectively, this study included 127 AHF patients who met the 2021 European Society of Cardiology Guidelines and 127 control individuals. Plasma miR-106a-5p levels were determined with RT-qPCR. Spearman correlation analysis was performed to evaluate the correlation of plasma miR-106a-5p levels with NT-proBNP and hs-CRP levels in AHF patients. All AHF patients were followed up for 1 year and allocated into poor and good prognosis groups, and plasma miR-106a-5p levels were compared. The diagnostic and prognostic value of plasma miR-106a-5p for AHF was assessed with a receiver-operating characteristic curve. Results Plasma miR-106a-5p was lowly expressed in AHF patients versus controls (0.53 ± 0.26 vs. 1.09 ± 0.46) and showed significant negative correlations with NT-proBNP and hs-CRP levels. Plasma miR-106a-5p level

MicroRNAs (miRNAs) are a class of small non-coding RNAs that may function as tumor suppressors or oncogenes. Alteration of their expression levels has been linked to a range of human malignancies, including cancer. The objective of this investigation is to assess the relative expression levels of certain miRNAs to distinguish between prostate cancer (PCa) from benign prostatic hyperplasia (BPH). Blood plasma was collected from 66 patients diagnosed with BPH and 58 patients with PCa. Real-time PCR technology was used to evaluate the relative expression among the two groups for miR-106a-5p and miR-148a-3p. The significant downregulation of both miRNAs in plasma from PCa versus BPH patients suggests their potential utility as diagnostic biomarkers for distinguishing between these conditions. The concurrent utilization of these two miRNAs slightly enhanced the sensitivity for discrimination among the two analyzed groups, as shown in ROC curve analysis. Further validation of these miRNAs in larger patient cohorts and across different stages of PCa may strengthen their candidacy as clinically relevant biomarkers for diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Background: It is essential to find reliable biomarkers for early diagnosis and prognosis of acute heart failure (AHF) for its mitigation. Currently, increasing attention is paid to the role of microRNAs (miRNAs/miRs) as diagnostic or prognostic markers for cardiovascular diseases. Since plasma miR-106a-5p has been observed to be downregulated in AHF, its value in the diagnosis and prognostic assessment of AHF deserves further exploration. Accordingly, this study analyzed the diagnostic and prognostic value of plasma miR-106a-5p in AHF patients. Methods: Prospectively, this study included 127 AHF patients who met the 2021 European Society of Cardiology Guidelines and 127 control individuals. Plasma miR-106a-5p levels were determined with RT-qPCR. Spearman correlation analysis was performed to evaluate the correlation of plasma miR-106a-5p levels with NT-proBNP and hs-CRP levels in AHF patients. All AHF patients were followed up for 1 year and allocated into poor and good prognosis groups, and plasma miR-106a-5p levels were compared. The diagnostic and prognostic value of plasma miR-106a-5p for AHF was assessed with a receiver-operating characteristic curve. Results: Plasma miR-106a-5p was lowly expressed in AHF patients versus controls (0.53 ± 0.26 vs. 1.09 ± 0.46) and showed significant negative correlations with NT-proBNP and hs-CRP levels. Plasma miR-106a-5p level < 0.655 could assist in AHF diagnosis. Plasma miR-106a-5p levels were markedly lower in poor-prognosis AHF patients than in good-prognosis patients. Plasma miR-106a-5p level < 0.544 could assist in predicting poor prognosis in AHF patients. Conclusion: Plasma miR-106a-5p is downregulated in AHF patients and could assist in diagnosis and poor prognosis prediction of AHF. [ABSTRACT FROM AUTHOR]

As one of the most frequent intracranial tumors, glioma showed invasive development and poor prognosis. lncRNAs have been illustrated to serve as biomarkers in various cancers. Whether the long non-coding RNA Prader Willi/Angelman region RNA 6 (PWAR6) was involved in glioma development and the underlying mechanism was investigated. PWAR6 in glioma was evaluated by polymerase chain reaction and its clinical significance was assessed with a series of statistical analyses. The biological function of PWAR6 was investigated with the cell counting kit 8 and Transwell assay. The potential underlying mechanism was studied with the luciferase reporter assay. The significant downregulation of PWAR6 was observed in glioma, which showed a close relationship with the major clinicopathological features and poor prognosis of patients. PWAR6 restrained cell growth, migration and invasion of glioma, which was alleviated by the overexpression of microRNA-106a-5p (miR-106a-5p). PWAR6 functioned as a prognostic biomarker and tumor suppressor of glioma through regulating miR-106a-5p. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a devastating stroke subtype. Baicalein (BAI) has been reported to be effective in ischemic stroke. The aim of the present study was to investigate the mechanism of BAI on brain injury after ICH. Firstly, ICH mouse models were established by injecting collagenase into the right of basal ganglia, followed by detection of neurobehavioral scores, brain edema, oxidative stress (OS) level, neuronal apoptosis and pathological changes. Average neurologic scores, brain water content, and blood–brain barrier permeability and MDA level in ICH mice were reduced after BAI treatment, while serum SOD and GSH-Px levels were increased and neuronal apoptosis and pathological injury of the brain tissues were mitigated. miR-106a-5p downregulation averted the effect of BAI on ICH mice. miR-106a-5p targeted PHLPP2 and PHLPP2 overexpression reversed the effect of BAI on ICH mice. BAI activated the Nrf2/ARE pathway by inhibiting PHLPP2 expression. In conclusion, BAI inhibited OS and protected against brain injury after ICH by activating the Nrf2/ARE pathway through the miR-106a-5p/PHLPP2 axis. [ABSTRACT FROM AUTHOR]

Abstract Background Acute cerebral infarction (ACI) is a common cerebrovascular disease. Previous studies have shown that some abnormally expressed microRNAs (miRNAs) play important roles in ACI. This study aimed to investigate the role of miR-106a-5p in the diagnosis and prognosis of ACI patients, and analyze the regulatory potential of miR-106a-5p on the inflammation of BV-2 microglial cells. Method Serum and cerebrospinal fluid (CSF) samples were collected from 98 ACI patients, and the expression of serum miR-106a-5p was analyzed using qRT-PCR. A receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of miR-106a-5p. The association of miR-106a-5p with ACI prognosis was evaluated using the logistic analysis. In vitro experiments were performed in BV-2 cells by oxygen glucose deprivation (OGD) treatment, and the effects of miR-106a-5p on BV-2 inflammation were assessed using an enzyme linked immunosorbent assay (ELISA). Result It was observed that miR-106a-5p was significantly upregulated in the serum and CSF of ACI patients (all P

Background: Acute cerebral infarction (ACI) is a common cerebrovascular disease. Previous studies have shown that some abnormally expressed microRNAs (miRNAs) play important roles in ACI. This study aimed to investigate the role of miR-106a-5p in the diagnosis and prognosis of ACI patients, and analyze the regulatory potential of miR-106a-5p on the inflammation of BV-2 microglial cells. Method: Serum and cerebrospinal fluid (CSF) samples were collected from 98 ACI patients, and the expression of serum miR-106a-5p was analyzed using qRT-PCR. A receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of miR-106a-5p. The association of miR-106a-5p with ACI prognosis was evaluated using the logistic analysis. In vitro experiments were performed in BV-2 cells by oxygen glucose deprivation (OGD) treatment, and the effects of miR-106a-5p on BV-2 inflammation were assessed using an enzyme linked immunosorbent assay (ELISA). Result: It was observed that miR-106a-5p was significantly upregulated in the serum and CSF of ACI patients (all P < 0.001), and had considerable diagnostic accuracy. The highest serum miR-106a-5p was observed in severe ACI cases, and miR-106a-5p expression was significantly increased in unfavorable prognosis patients. Serum and CSF expression of miR-106a-5p was positively correlated with proinflammatory cytokines in ACI patients, and the inflammation of OGD-induced BV-2 cells was suppressed by miR-106a-5p reduction. Conclusion: MiR-106a-5p is overexpressed in ACI patients and may serve as a diagnostic and prognostic biomarker for ACI. Furthermore, miR-106a-5p may be involved in ACI progression by regulating neuroinflammation. [ABSTRACT FROM AUTHOR]

Peizhang Wu,1,2 Jun Guo,2 Hongwei Yang,2 Debin Yuan,2 Chaoxiang Wang,2 Zhong Wang1 1Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 2Department of Neurosurgery, Yancheng First People’s Hospital, Yancheng, 224000, People’s Republic of ChinaCorrespondence: Zhong Wang, Department of Neurosurgery, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215006, People’s Republic of China, Email wangzhong6439@163.comBackground: Hypoxia is a frequent feature of solid tumors which significantly affects the efficacy of treatments such as chemotherapy. In addition, exosomes from hypoxic cancer cells could contribute to the chemoresistance of tumor cells through carrying miRNAs. It has been shown that miR-106-5p level was upregulated in glioma. However, whether exosomes derived from hypoxic glioma cells could affect temozolomide (TMZ) resistance in glioma through carrying miR-106a-5p remains unexplored.Methods: Exosomes were isolated from glioma cells under normoxia or hypoxia condition. EdU staining and flow cytometry assays were used to assess the cell proliferation and cell apoptosis. The relation between miR-106a-5p and PTEN was investigated by dual luciferase assay.Results: MiR-106a-5p was enriched in exosomes derived from hypoxic glioma cells compared to exosomes from cells under normoxia condition. Additionally, hypoxic glioma cells were able to transfer exosomes to glioma cells, resulting in a significant increase of miR-106a-5p level in cells. TMZ remarkably suppressed glioma cell proliferation and triggered cell apoptosis. However, hypoxic glioma cell-derived exosomes markedly promoted the proliferation and suppressed the apoptosis in TMZ-treated glioma cells, and miR-106a-5p inhibitor was able to abolish these phenomena. Meanwhile, PTEN was verified to be a direct target of miR-106a-5p. Furthermore, TMZ elevated PTEN and Bax level and reduced p-Akt level in glioma cells, whereas these changes were reversed by hypoxia glioma cell-derived exosomes. Furthermore, hypoxia glioma cell-derived exosomes reduced the sensitivity of glioma cells to TMZ in vivo via downregulating PTEN.Conclusion: Collectively, exosomal miR-106a-5p derived from hypoxia glioma cells could reduce the sensitivity of glioma cells to TMZ through downregulating PTEN. Thus, our study might provide new strategies for improving the clinical efficacy of TMZ on glioma.Keywords: cancer, hypoxia, miR-106a-5p, chemosensitivity

Aims: This study aims to investigate the function of positive feedback loops involving noncoding RNA in diabetic wound healing. Methods: We developed a mouse diabetic wound model to confirm that hyperglycemia can impair wound healing. We also used an in vitro keratinocyte model in high-glucose conditions to investigate the mechanism of delayed wound healing. Results:MALAT1 was decreased in diabetic mouse wound tissue and can promote keratinocyte biological functions. MALAT1 could bind to miR-106a-5p to modulate the expression of ZNF148, a target gene of miR-106a-5p. Surprisingly, ZNF148 bound to a region in the MALAT1 promoter to stimulate gene expression. Conclusion: ZNF148-activated MALAT1 increases ZNF148 expression by competitively binding miR-106a-3p, generating a positive feedback loop that enhances keratinocyte function. Delayed wound repair is a leading cause of diabetic foot ulcers. However, the molecular mechanism underlying impaired wound healing in diabetes is unclear. In our study we found that a positive feedback loop consisting of MALAT1, miR-106a-5p and ZNF148 could promote chronic wound repair. In diabetic skin tissues, MALAT1 levels were lower, causing impairments in skin cell function. On a molecular level, MALAT1 can bind miR-106a-5p to increase ZNF148 levels. Surprisingly, ZNF148 can bind the promoter of MALAT1 to reverse the decline of MALAT1 levels in diabetic wounds. Our findings advance our understanding of chronic diabetic wounds and, more crucially, open new therapeutic possibilities for this disease. [ABSTRACT FROM AUTHOR]

Abstract Background Diabetic foot ulcer (DFU) is a chronic infectious disease caused by diabetes mellitus (DM). Angiogenesis plays the decisive role in wound healing of DFU. Adipose-derived stem cells (ADSCs) can ameliorate angiogenesis in DFU by exosomes. This study aims to determine the mechanism of exosomes from mmu_circ_0001052-modified ADSCs in angiogenesis of DFU. Methods HUVECs were induced by high glucose and mice stimulated using STZ injection during high-fat feeding, which were treated with exosomes derived from mmu_circ_0001052-modified ADSCs. Real-time PCR determined the expression of gene and western blot determined protein levels. Proliferation, migration, apoptosis and angiogenesis of HUVECs were studied by MTT assay, transwell test, flow cytometry and tube formation experiment, respectively. Histological lesion of wound was determined by HE staining. Results The expression of circ_0001052 was upregulated in ADSCs and miR-106a-5p elevated in high glucose-induced HUVECs. Exosomal mmu_circ_0001052 significantly accelerated wound healing in mice with DFU. Also, exosomal mmu_circ_0001052 evoked the reduction of miR-106a-5p and the elevation of FGF4 in high glucose-induced HUVECs and wound tissue of DFU mice. Exosomal mmu_circ_0001052 was determined to sponge miR-106a-5p that targeted FGF4 in DFU. In high glucose-induced HUVECs, exosomal mmu_circ_0001052 inhibited apoptosis and miR-106a-5p expression, and meanwhile promoted proliferation, migration, angiogenesis and expressions of FGF4, VEGF and p-p38/p38, which were reversed by miR-106a-5p elevation. Conclusion Mmu_circ_0001052 in ADSCs-derived exosomes promote angiogenesis of DFU via miR-106a-5p and FGF4/p38MAPK pathway. Graphical Abstract

Atherosclerosis is the most common arterial disease and is closely related to vascular calcification. CircHIPK3 has been implicated in atherosclerosis development, but the possible downstream regulatory mechanisms remain unclear. The levels of circHIPK3, miR-106a and MFN2 in tissues and blood samples of patients with atherosclerosis were detected by RT-qPCR. The levels of circHIPK3, miR-106a and MFN2 were detected by RT-qPCR and the expression levels of MFN2, osteogenic and cartilage differentiation marker proteins were detected by western blot in vitro. ALP staining, Alizarin Red staining, and calcium content detection evaluated the degree of osteogenic differentiation of cells. Alcian blue staining detected the level of cell cartilage differentiation. Luciferase detected the targeting relationship between circHIPK3 and miR-106a-5p, as well as miR-106a-5p and MFN2. CircHIPK3 and MFN2 were low expressed and miR-106a-5p was highly expressed in tissues and blood samples of patients with atherosclerosis, as well as vascular smooth muscle cell (VSMC) with osteogenic and cartilage differentiation. Overexpression of circHIPK3 reduced the cell mineralization and calcium content. Overexpression of circHIPK3 inhibited osteogenic differentiation by decreasing ALP activity, RUNX2, and OPG expression, and increasing SM22α and SMA level. What's more, overexpression of circHIPK3 decreased the chondrogenic differentiation by inhibiting the protein level of SOX9, aggrecan, and collagen II. CircHIPK3 targeted miR-106a-5p and miR-106a-5p targeted MFN2. MiR-106a-5p overexpression or MFN2 depletion repressed the effect of circHIPK3 overexpression on VSMC calcification. CircHIPK3 regulated osteogenic and cartilage differentiation of VSMC via miR-106a-5p/MFN2 axis, indicating a target for treating vascular calcification. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of lncRNA FGD5-AS1 on oxidized low-density lipoprotein (ox-LDL)-induced vascular endothelial cell damage and its regulatory effect on miR-106a-5p. Methods Ox-LDL was used to induce human umbilical vein endothelial cells(HUVECs) to establish a cellular injury model. pcDNA-FGD5-AS1, anti-miR-106a-5p and its negative control were transfected into HUVECs and then added to ox-LDL-treated cells. pcDNA-FGD5-AS1 was co-transfected with miR-NC and miR-106a-5p mimics to HUVECs, then added ox-LDL to treat cells. RT-qPCR was used to detect the expression of FGD5-AS1 and miR-106a-5p. The level of MDA, SOD, and CAT was tested with commercially available kit. Flow cytometry was used to detect the apoptosis rate. The dual luciferase reporter gene experiment was used to detect the targeting relationship between FGD5-AS1 and miR-106a-5p. Western blot was used to detect the protein expression of cleaved caspase-3 and cleaved caspase-9. Results The expression of FGD5-AS1 mRNA in HUVECs induced by ox-LDL decreased (P＜0.05) while the expression of miR-106a-5p mRNA increased (P＜0.05). Both transfection of pcDNA-FGD5-AS1 and transfection of anti-miR-106a-5p reduced the level of MDA, apoptosis rate and protein level of cleaved caspase-3, cleaved caspase-9 in HUVECs induced by ox-LDL(P＜0.05),enhanced the activity of SOD and CAT (P＜0.05). FGD5-AS1 could target at miR-106a-5p. Co-transfection of pcDNA-FGD5-AS1 and miR-106a-5p mimics could reverse the effect of pcDNA-FGD5-AS1 on ox-LDL-induced HUVECs apoptosis and oxidative stress. Conclusions Over-expression of FGD5-AS1 may inhibit oxidative stress and apoptosis through targeted regulation of miR-106a-5p, thereby reducing ox-LDL-induced vascular endothelial cell damage.

Tumor-derived extracellular vesicles (EVs) promote ovarian cancer (OC) metastasis by carrying microRNAs (miRs). This study investigated the mechanism of miR-106a-5p carried by OC cell-derived EVs in OC. miR-106a-5p expression in OC tissues and cells was measured. EVs were extracted from SKOV3 cells and normal cells. The internalization of EVs in OC cells was observed. OC cells were treated with SKOV3-EVs or SKOV3-EVs overexpressing miR-106a-5p to detect the proliferation, migration, and invasion. The expression levels of miR-106a-5p, KLF6, and PTTG1 were detected and their binding relationships were identified. Combined experiments were designed to detect the effects of KLF6 and PTTG1 on OC cells. A xenograft tumor experiment was performed to verify the mechanism of EVs-miR-106a-5p and KLF6 in OC metastasis. Consequently, miR-106a-5p was enhanced in OC and correlated with OC metastasis. SKOV3-EVs promoted the proliferation, migration, and invasion of OC cells. Mechanistically, EVs carried miR-106a-5p into other OC cells, inhibited KLF6, reduced the binding of KLF6 to the PTTG1 promoter, and upregulated PTTG1 transcription. Overexpression of KLF6 or silencing of PTTG1 attenuated the promoting effect of EVs-miR-106a-5p on OC cells. EVs-miR-106a-5p facilitated OC metastasis via the KLF6/PTTG1 axis. To conclude, OC cell-derived EVs facilitated the progression and metastasis of OC via the miR-106a-5p/KLF6/PTTG1 axis. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot ulcer (DFU) is a chronic infectious disease caused by diabetes mellitus (DM). Angiogenesis plays the decisive role in wound healing of DFU. Adipose-derived stem cells (ADSCs) can ameliorate angiogenesis in DFU by exosomes. This study aims to determine the mechanism of exosomes from mmu_circ_0001052-modified ADSCs in angiogenesis of DFU. Methods: HUVECs were induced by high glucose and mice stimulated using STZ injection during high-fat feeding, which were treated with exosomes derived from mmu_circ_0001052-modified ADSCs. Real-time PCR determined the expression of gene and western blot determined protein levels. Proliferation, migration, apoptosis and angiogenesis of HUVECs were studied by MTT assay, transwell test, flow cytometry and tube formation experiment, respectively. Histological lesion of wound was determined by HE staining. Results: The expression of circ_0001052 was upregulated in ADSCs and miR-106a-5p elevated in high glucose-induced HUVECs. Exosomal mmu_circ_0001052 significantly accelerated wound healing in mice with DFU. Also, exosomal mmu_circ_0001052 evoked the reduction of miR-106a-5p and the elevation of FGF4 in high glucose-induced HUVECs and wound tissue of DFU mice. Exosomal mmu_circ_0001052 was determined to sponge miR-106a-5p that targeted FGF4 in DFU. In high glucose-induced HUVECs, exosomal mmu_circ_0001052 inhibited apoptosis and miR-106a-5p expression, and meanwhile promoted proliferation, migration, angiogenesis and expressions of FGF4, VEGF and p-p38/p38, which were reversed by miR-106a-5p elevation. Conclusion: Mmu_circ_0001052 in ADSCs-derived exosomes promote angiogenesis of DFU via miR-106a-5p and FGF4/p38MAPK pathway. [ABSTRACT FROM AUTHOR]

Background: Sulfur mustard as a chemical warfare agent causes short and long-term pulmonary complications in its victims. MicroRNAs are known to act as remarkable regulators of biological pathways, monitoring, and treatment of diseases including respiratory problems. In this study, we investigated the expression of miR-106a-5p and miR-106b-5p, two regulators of TGF-ß signaling, as well as their target molecule, TGFß1I1, in peripheral blood mononuclear cells from SM-exposed individuals. Materials and Methods: A total of 70 veterans with SM-induced pulmonary complications were examined and compared to 35 gender and age-matched healthy controls. After clinical examination and pulmonary function tests, the severity of pulmonary complications was classified. Total RNA was extracted from PBMCs and the purity of extracted RNA samples was evaluated by a NanoDrop 2000. The miR-106a-5p, miR-106b-5p, and TGFß1I1 expression levels were measured by real-time RT-PCR. Results: The miR-106a-5p expression levels were significantly increased in both mild (P=0.015) and severe groups compared with the control group. The miR-106b-5p expression levels were considerably elevated in the severe group TGFß1I1 expression levels were notably reduced in the severe group compared with the control group. Although, a slight decrease in TGFß1I1 expression levels was observed in the mild group compared with the control. Conclusion: Our results indicate that exposure to sulfur mustard affects the expression of miR-106a-5p, miR-106b-5p, and their target gene, TGFβ1I1, in peripheral blood mononuclear cells. Considering the role of TGFβ1I1 in the regulation of TGF-β signaling, the mentioned changes might point to a potential mechanism by which SM exposure causes chronic pulmonary complications. In a ROC analysis, miR-106a-5p and miR-106b-5p potentially turned out to be a suitable diagnostic biomarker in the mild and severe categories of patients. Although, miR-106a-5p could be considered a better biomarker than miR-106b-5p. [ABSTRACT FROM AUTHOR]

Abstract Background Lung cancer mainly includes non‐small cell lung cancer (NSCLC). Lung adenocarcinoma (LUAD) is the main subtype of NSCLC. Long non‐coding RNAs (LncRNAs) had been found to exert numerous functions on the progressions of cancers. MicroRNAs often exist as the target of LncRNAs to regulate a series of signaling pathways in human. We explored the effects and molecular mechanism of LncRNA SGMS1‐AS1 on the procedures of LUAD cells. Methods The ENCORI and GEPIA databases were used to analyze the differences in SGMS1, miR‐106a‐5p, and MYLIP between LUAD and normal tissue. Their expression levels were examined by RT‐PCR. CCK8, colony formation, migration, and invasion assay were conducted in LUAD cells which had silenced SGMS1‐AS1. To verify the relationship between SGMS1‐AS1, miR‐106a‐5p, and MYLIP, we overexpressed miR‐106a‐5p inhibitor or MYLIP in LUAD cells after decreasing SGMS1‐AS1 and repeated the above assays. Results SGMS1‐AS1 was downregulated in LUAD tissue as well as cells, which was related to good prognosis of patients with lung adenocarcinoma. Additionally, knockdown of SGMS1‐AS1 promoted proliferation, migration, invasion, and epithelial mesenchymal transition (EMT) progression of LUAD cells, which meant that SGMS1‐AS1 inhibited the progression of LUAD cells. Furthermore, miR‐106a‐5p was the direct target of SGMS1‐AS1 and transfecting miR‐106a‐5p inhibitor could reversed the impact induced by knockdown of SGMS1‐AS1. Subsequently, we found that MYLIP was the target of miR‐106a‐5p, which was negatively correlated with miR‐106a‐5p, but had high positive correlation with SGMS1‐AS1. Consistently, overexpression MYLIP partly eliminated the effects on A549 cells induced by silencing of SGMS1‐AS1. Conclusion LncRNA SGMS1‐AS1 inhibits the proliferation, invasion, migration and EMT progression of LUAD cells via targeting miR‐106a‐5p/MYLIP axis.

Liver cancer presents a challenge in today’s healthcare system. This study aimed at investigating the effects of Fer-1 like family member 4 (FER1L4) on chemotherapy resistance and liver cancer development by using clinically collected liver cancer tissues and commercially purchased human liver cancer cisplatin-resistant cell line HUH-7/DDP. Bioinformatics analysis, dual luciferase reporter gene assay, and RNA pull-down were applied to predict and verify the possible binding relationships. The expressions of FER1L4, E2F transcription factor 1 (E2F1), microRNA-106a-5p (miR-106a-5p), or miR-372-5p were altered in the cells, followed by flow cytometry, Cell Counting Kit-8 (CCK-8), and Transwell assays to evaluate apoptotic, proliferative, and invasive abilities in vitro and nude mice xenografts to observe tumor growth in vivo. FER1L4 was highly expressed and miR-106-5p and miR-372-5p were poorly expressed in tumor cells and tissues. FER1L4 knockdown or the overexpression of miR-106-5p and miR-372-5p inhibited the cancerous cell proliferation and invasion while promoting apoptosis. FERIL4 silencing increased the miR-106-5p/miR-372-5p expression to inhibit the E2F1-activated nuclear factor κB (NF-κB) pathway. Besides, overexpressing FER1L4 led to an increased tumor growth in nude mice, which was reversed by the NF-κB inhibitor pyrollidine dithiocarbamate (PDTC). In conclusion, the results indicated that FER1L4 could inhibit the expression of miR-106a-5p/miR-372-5p, to activate E2F1-mediated NF-κB pathway, leading to drug resistance in liver cancer.

Nasopharyngeal carcinoma (NPC) is prevalent in East Asia and causes increased health burden. Elucidating the regulatory mechanism of NPC progression is important for understanding the pathogenesis of NPC and developing novel therapeutic strategies. Nasopharyngeal carcinoma and normal tissues were collected. Nasopharyngeal carcinoma cell proliferation, migration, and invasion were evaluated using CCK‐8, colony formation, wound healing, and transwell assays, respectively. A xenograft mouse model of NPC was established to analyze NPC cell growth and metastasis in vivo. The expression of miR‐106a‐5p, FBXW7, TRIM24, and SRGN was determined with RT‐qPCR and Western blot. MiR‐106a‐5p, TRIM24, and SRGN were upregulated, and FBXW7 was downregulated in NPC tissues and cells. Exosomal miR‐106a‐5p could enter NPC cells, and its overexpression promoted the proliferation, migration, invasion, and metastasis of NPC cells, which were suppressed by knockdown of exosomal miR‐106a‐5p. MiR‐106a‐5p targeted FBXW7 to regulate FBXW7‐mediated degradation of TRIM24. Furthermore, TRIM24 regulated SRGN expression by binding to its promoter in NPC cells. Suppression of exosomal miR‐106a‐5p attenuated NPC growth and metastasis through the FBXW7‐TRIM24‐SRGN axis in vivo. Exosomal miR‐106a‐5p accelerated the progression of NPC through the FBXW7‐TRIM24‐SRGN axis. Our study elucidates novel regulatory mechanisms of NPC progression and provides potential exosome‐based therapeutic strategies for NPC. [ABSTRACT FROM AUTHOR]

Protein tyrosine phosphatase non-receptor type 12 (PTPN12) is abnormally expressed in many human cancers. However, its role in hepatocellular carcinoma (HCC) is indeterminate. In this study, immunohistochemistry and Western blot were adopted to detect PTPN12 protein expression in HCC tissues and cell lines. MiR-106a-5p and PTPN12 mRNA expressions were determined by quantitative real-time polymerase chain reaction (qRT-PCR). siRNA was used to knockdown PTPN12 expression in HCC cells, and the multiplication, migration, and invasion of HCC cells were determined by cell counting kit 8 (CCK-8) and Transwell assays. The interaction between PTPN12 and miR-106a-5p was verified by dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. In the present study, we demonstrated that PTPN12 expression in HCC tissues and cells was significantly decreased, which was associated with the tumor size, TNM stage, and lymph node metastasis of HCC patients. Functionally, knocking down PTPN12 significantly promoted the multiplication, migration, invasion, and epithelial-mesenchymal transition (EMT) of HCC cells. PTPN12 was identified as the direct target of miR-106a-5p, and its expression was negatively modulated by miR-106a-5p. Besides, PTPN12 counteracted the promoting effects of miR-106a-5p on the viability, migration, invasion, and EMT of HCC cells. In conclusion, this study substantiates that PTPN12 inhibits the growth, migration, invasion, and EMT of HCC cells, and miR-106a-5p contributes to its dysregulation in HCC. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC), a subclass of cancers of the neck and head, is a predominant cause of cancer‐associated death worldwide. Hence, there is a critical need for research into NPC‐related treatment strategies. Cisplatin is a promising therapy option for NPCs and other cancers that is frequently utilized. Some patients acquire resistance to cisplatin therapy, which complicates the successful use of cisplatin treatment in NPCs. Although exosomal transfer of oncogenic miRNAs has been shown to improve recipient cell proliferation, metastasis and chemoresistance, the molecular mechanism behind this effect on NPC has yet to be fully understood. Exosomal microRNAs (miRNAs) from cisplatin‐resistant cells were identified as significant mediators of chemoresistance in NPC cells in this investigation. Initially, we found that exosomal miR‐106a‐5p levels in the serum of chemoresistant and last‐cycle patients were greater than in that of non‐resistant and first‐cycle patients. Also, exosomal miR‐106a‐5p enhanced the proliferative ability of NPC cells. Mechanistically, exosomal miR‐106a‐5p targets ARNT2, which further activates AKT phosphorylation, and thus promotes NPC cell proliferation, decreases apoptosis and in turn regulates tumorigenesis. We found similar results using in vivo NPC models, where exosomal miR‐106a‐5p through regulation of ARNT2 (aryl hydrocarbon receptor nuclear translocator 2) promoted tumorigenesis. Taken together, these findings indicate that exosomal miR‐106a‐5p could be a promising diagnostic biomarker and drug target for patients with NPC. [ABSTRACT FROM AUTHOR]

Recently, an increasing number of studies have reported that dysregulation of circular RNA (circRNA) expression plays critical roles in the progression of several cancers, including colorectal cancer (CRC). However, the detailed molecular mechanisms of circRNAs involvement in CRC remain largely unknown. Here, we confirmed that the level of circEGFR was significantly increased in CRC tissues compared to matched adjacent non-tumor tissues, and a high level of circEGFR was correlated with poor clinicopathological characteristics and poor prognosis in patients with CRC. Moreover, increased circEGFR expression promoted CRC cell proliferation, migration, and invasion in vitro. Mechanistically, circEGFR acted as a ceRNA for miR-106a-5p to relieve the repressive effect of miR-106a-5p on DDX5 mRNA. Moreover, circEGFR enhanced DDX5 expression, thereby upregulating p-AKT levels. Together, these findings showed that circEGFR promoted CRC cell proliferation, migration, and invasion through the miR-106a-5p/DDX5/AKT axis, and may serve as a promising diagnostic marker and therapeutic target for CRC patients.

Sepsis is an inflammatory disorder and leads to severe acute kidney injury (AKI). Circular RNAs (circRNAs) have been identified as a critical type of regulatory noncoding RNAs (ncRNAs) that present the important functions in various diseases. In this study, we identified a novel circRNA circTLK1 in the regulation of sepsis-induced AKI. We observed that circTLK1 expression was elevated in the cecal ligation and puncture (CLP) rat model compared with that in the control rats. The urine levels of neutrophil gelatinase–associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) and the serum levels of creatinine (sCr) and blood urea nitrogen (BUN) were increased by the CLP treatment in the rats but were blocked by the circTLK1 shRNA. The circTLK1 shRNA reduced the CLP-induced kidney injury in the rats. The circTLK1 knockdown repressed oxidation stress, inflammation, and apoptosis in the sepsis-related AKI rat model. Moreover, lipopolysaccharide (LPS) treatment increased the production of TNF-α, IL-1β, and IL-6 in the HK-2 cells, while the circTLK1 shRNA could attenuate the enhancement in the cells. Bax and cleaved caspase-3 expression was upregulated, but Bcl-2 expression was downregulated by the LPS in the HK-2 cells, in which circTLK1 depletion reversed this effect in the cells. The depletion of circTLK1 attenuated the LPS-induced apoptosis in the HK-2 cells. CircTLK1 enhanced HMGB1 expression by sponging miR-106a-5p in the HK-2 cells, and miR-106a-5p and HMGB1 were involved in circTLK1-meidated injury of LPS-treated cells. Therefore, we concluded that circTLK1 contributed to sepsis-associated AKI by regulating inflammation and oxidative stress through the miR-106a-5p/HMGB1 axis. CircTLK1 and miR-106a-5p may be employed as the potential targets for the treatment of AKI.

Objective To observe the effect of microRNA-106a-5p（miR-106a-5p）on the drug resistance of gastric cancer cells to cisplatin（DDP）through targeted regulation of extracellular signal-regulated kinase 2（ERK2）,and to explore its possible molecular mechanism. Methods Gastric cancer cell line MGC-803 DDP-resistant cell line MGC-803/ DDP was established. QRT-PCR was used to detect the expression of miR-106a-5p and ERK2 in gastric cancer cell line MGC-803 and drug-resistant cell line MGC-803/DDP. The online bioinformatics software starBase and Targetscan7. 2 were used to predict the binding site of miR-106a-5p and ERK2，and luciferase report experiment was used to verify the targeted regulation between them. The drug-resistant cell line MGC-803/DDP was divided into the mimic group（transfected with miR-106a-5p mimic），ERK2 group（transfected with plasmid pcDNA3. 1-ERK2），mimic+ ERK2 group（co-transfected with miR-106a-5p mimic and pcDNA3. 1-ERK2 plasmid）, and NC group（ blank control group）. EdU assay was used to observe the cell proliferation ability of each group. Flow cytometry was used to detect the level of apoptosis in each group. Transwell test was used to detect the cell invasion ability of each group. Western blotting was used to detect the ex⁃ pression changes of proliferation and apoptosis-related proteins Cyclin D1，Caspase-3，epithelial-mesenchymal transitionrelated proteins E-cadherin，N-cadherin and Vimentin，and multiple drug resistance gene（MDR1）. MTT assay was used to detect drug resistance of cells to DDP. Results The relative expression of miR-106a-5p was significantly lower, while ERK-2 mRNA expression level was significantly higher in the MGC-803/DDP cells than those of the MGC-803 cells（both P<0. 05）. Forecast showed that there was a binding site between ERK2 gene sequence and miR-106a-5p. The results of the luciferase experiment showed that miR-106a-5p could negatively regulate ERK2 expression. EdU positive cell number was in the following order：ERK2 group>NC group>mimic+ERK2 group>mimic group, the number of apoptosis cells：mimic group>NC group>mimic+ERK2 group>ERK2 group，and the number of adherent cells：ERK2 group>NC group>mimic+ ERK2 group >mimic group（all P<0. 05）；Cyclin D1，N-cadherin，Vimentin，MDR1 expression was as follows：ERK2 group>mimic+ERK2 group>NC group>mimic group，Caspase3，E-cadherin expression：mimic group>mimic+ERK2 group>NC group>ERK2 group（all P<0. 05），and IC50：ERK2 group>NC group>mimic+ERK2 group>mimic group（all P< 0. 05）. Conclusion MiR-106a-5p reduces the drug resistance of gastric cancer cells to DDP by targeting the expression of ERK2，and this mechanism may be related to changing the expression of proliferation and apoptosis-related proteins, reversing the process of epithelial-mesenchymal transition and reducing the level of drug resistance gene MDR1. [ABSTRACT FROM AUTHOR]

• This study found that adipose-derived stem cell exosomes can promote M2 polarization of macrophages through the transmission of LncRNA DLEU2. • The aim of this study was to explore the molecular mechanism of adipose-derived stem cell exosomes in sepsis-induced lung injury. • Through high-throughput sequencing, this study found that LncRNA DLEU2 is enriched in exosomes of sepsis lung tissue. • This study confirmed that ADSC-Exos can promote M2 polarization of macrophages and alleviate inflammation and apoptosis of lung injury cells. This study investigates the molecular mechanisms by which extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ADSCs) promote M2 polarization of macrophages and thus reduce lung injury caused by sepsis. High-throughput sequencing was used to identify differentially expressed genes related to long non-coding RNA (lncRNA) in ADSC-derived EVs (ADSC-EVs) in sepsis lung tissue. Weighted gene co-expression network analysis (WGCNA) was employed to predict the downstream target genes of the lncRNA DLEU2. The RNAInter database predicted miRNAs that interact with DLEU2 and LXN. Functional and pathway enrichment analyses were performed using GO and KEGG analysis. A mouse model of sepsis was established, and treatment with a placebo or ADSC-EVs was administered, followed by RT-qPCR analysis. ADSC-EVs were isolated and identified. In vitro cell experiments were conducted using the mouse lung epithelial cell line MLE-12, mouse macrophage cell line RAW264.7, and mouse lung epithelial cell line (LEPC). ADSC-EVs were co-cultured with RAW264.7 and MLE-12/LEPC cells to study the regulatory mechanism of the lncRNA DLEU2. Cell viability, proliferation, and apoptosis of lung injury cells were assessed using CCK-8, EdU, and flow cytometry. ELISA was used to measure the levels of inflammatory cytokines in the sepsis mouse model, flow cytometry was performed to determine the number of M1 and M2 macrophages, lung tissue pathology was evaluated by H&E staining, and immunohistochemistry was conducted to examine the expression of proliferation- and apoptosis-related proteins. High-throughput sequencing and bioinformatics analysis revealed enrichment of the lncRNA DLEU2 in ADSC-EVs in sepsis lung tissue. Animal and in vitro cell experiments showed increased expression of the lncRNA DLEU2 in sepsis lung tissue after treatment with ADSC-EVs. Furthermore, ADSC-EVs were found to transfer the lncRNA DLEU2 to macrophages, promoting M2 polarization, reducing inflammation response in lung injury cells, and enhancing their viability, proliferation, and apoptosis inhibition. Further functional experiments indicated that lncRNA DLEU2 promotes M2 polarization of macrophages by regulating miR-106a-5p/LXN, thereby enhancing the viability and proliferation of lung injury cells and inhibiting apoptosis. Overexpression of miR-106a-5p could reverse the biological effects of ADSC-EVs-DLEU2 on MLE-12 and LEPC in vitro cell models. Lastly, in vivo animal experiments confirmed that ADSC-EVs-DLEU2 promotes high expression of LXN by inhibiting the expression of miR-106a-5p, further facilitating M2 macrophage polarization and reducing lung edema, thus alleviating sepsis-induced lung injury. lncRNA DLEU2 in ADSC-EVs may promote M2 polarization of macrophages and enhance the viability and proliferation of lung injury cells while inhibiting inflammation and apoptosis reactions, thus ameliorating sepsis-induced lung injury in a mechanism involving the regulation of the miR-106a-5p/LXN axis. [ABSTRACT FROM AUTHOR]

Bao Hai,1 Yunlong Ma,2 Xiaoyu Pan,1 Lei Yong,1 Chen Liang,1 Guanping He,1 Chenlong Yang,1 Bin Zhu,2 Xiaoguang Liu1 1Department of Orthopedics, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2The Center for Pain Medicine, Peking University Third Hospital, Beijing 100191, People’s Republic of China Background: Disc degeneration (DD) is one of the common diseases worldwide, which deeply influences normal life and leads to excruciating pain. However, an effective treatment for DD is still not identified.Method: The present study systemically examined the effect of melatonin on annulus fibrosus (AF) cells of patients with DD.Results: Melatonin had the effect of promoting proliferation, inducing autophagy, and suppressing apoptosis on AF cells of patients with DD. Moreover, melatonin contributed to the translation and transcription of autophagy-related protein ATG7 and inhibited the function of miR-106a-5p in AF cells. In addition, the results suggested that miR-106a-5p mediated the expression of ATG7 by directly binding to its 3'UTR in AF cells.Conclusion: This research not only gained a deep insight of melatonin mode of action, but also indicated its potential target signaling pathway in AF cells. Keywords: disc degeneration, melatonin, ATG7, miR-106a-5p

Abstract Background Sex differences in the incidence and prognosis of respiratory diseases have been reported. Studies have shown that women are at increased risk of adverse health outcomes from air pollution than men, but sex-specific immune gene expression patterns and regulatory networks have not been well studied in the lung. MicroRNAs (miRNAs) are environmentally sensitive posttranscriptional regulators of gene expression that may mediate the damaging effects of inhaled pollutants in the lung, by altering the expression of innate immunity molecules. Methods Male and female mice of the C57BL/6 background were exposed to 2 ppm of ozone or filtered air (control) for 3 h. Female mice were also exposed at different stages of the estrous cycle. Following exposure, lungs were harvested and total RNA was extracted. We used PCR arrays to study sex differences in the expression of 84 miRNAs predicted to target inflammatory and immune genes. Results We identified differentially expressed miRNA signatures in the lungs of male vs. female exposed to ozone. In silico pathway analyses identified sex-specific biological networks affected by exposure to ozone that ranged from direct predicted gene targeting to complex interactions with multiple intermediates. We also identified differences in miRNA expression and predicted regulatory networks in females exposed to ozone at different estrous cycle stages. Conclusion Our results indicate that both sex and hormonal status can influence lung miRNA expression in response to ozone exposure, indicating that sex-specific miRNA regulation of inflammatory gene expression could mediate differential pollution-induced health outcomes in men and women.

Objective(s): Multiple sclerosis (MS) is considered as a chronic type of an inflammatory disease characterized by loss of myelin of CNS.Recent evidence indicates that Interleukin 17 (IL-17)-producing T helper cells (Th17 cells) population are increased and regulatory T cells (Treg cells) are decreased in MS. Despite extensive research in understanding the mechanism of Th17 and Treg differentiation, the role of microRNAs in MS is not completely understood. Thereby, as a step closer, we analyzed the expression profile of miR-9-5p and miR-106a-5p, and protein level of retinoic acid receptor (RAR)-related orphan receptor C (RORC; Th17 master transcription factor) as direct target of miR-106a-5p and forkhead box P3 (FOXP3; Treg master transcription factor) as indirect target of miR-9-5p in CD4+ T cells in two groups of relapsing and remitting in our relapsing-remitting MS (RR-MS) patients. Materials and Methods:Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to assess the expression of miRNAs and mRNAs, in 40 RR-MS patients and 11 healthy individuals. Thus, FOXP3 and RAR-related orphan receptor γt (RORγt) was assessed in CD4+T-cells by flow cytometry. We also investigated the role of these miRNAs in Th17/Treg differentiation pathway through bioinformatics tools. Results: An up-regulation of miR-9-5p and down-regulation of miR-106a-5p in relapsing phase of MS patients were observed compared to healthy controls. RORC and FOXP3 wereup-regulated in relapsing and remitting phases of MS, respectively. Conclusion: Expression pattern of miR-9-5p and miR-106a-5p and their targets suggest a possible inducing role of miR-9-5p and suppressing role of miR-106a-5p in differentiation pathway of Th17 cells during MS pathogenesis.

Oral squamous cell carcinoma (OSCC) is the most commonly diagnosed oral cavity malignancy. A handful of circular RNAs (circRNAs) have recently shown to act as crucial regulators in OSCC, including circRNA plasmacytoma variant translocation 1 (circ-PVT1). However, further exploration is still needed for the underlying functional mechanism behind circ-PVT1 in OSCC. The levels of circ-PVT1, microRNA-106a-5p (miR-106a-5p) and hexokinase II (HK2) were all examined applying with quantitative real-time polymerase chain reaction (qRT-PCR). Cellular analyses (cell viability, apoptosis, metastasis and glycolysis) in vitro were performed via cell counting kit-8 (CCK-8), flow cytometry, transwell migration/invasion assays and glycolysis-related indications (glucose consumption, lactate production and ATP/ADP ratio). HK2 protein level was measured through western blot. Dual-luciferase reporter assay was conducted to study the interplay between miR-106a-5p and circ-PVT1 or HK2. Xenografts in mice were used for analyzing circ-PVT1 in vivo. Circ-PVT1 was expressed with abnormal high level while miR-106a-5p was down-regulated in OSCC tissues and cells. Circ-PVT1 knockdown reduced OSCC cell growth, metastasis and glycolysis. Moreover, circ-PVT1 acted in OSCC by functioning as a miR-106a-5p sponge. HK2 was a target of miR-106a-5p and miR-106a-5p played an anti-tumor role in OSCC by inhibiting HK2. Furthermore, HK2 could be regulated by circ-PVT1 via targeting miR-106a-5p. In xenograft models of mice, down-regulation of circ-PVT1 retarded tumorigenesis via the miR-106a-5p/HK2 axis. Our works suggested that circ-PVT1 directly combined with miR-106a-5p to mediate HK2 level, consequently regulating cellular behaviors in OSCC as a tumor promoter. [ABSTRACT FROM AUTHOR]

Although stable microRNAs (miRNAs) are present in human peripheral blood and have been considered as novel biomarkers for various diseases. But there is little research about miRNAs as biomarkers of mesangial proliferative glomerulonephritis (MsPGN). This study aimed to identify whether there exist disordered circulating miRNAs that can function as biomarkers for MsPGN disease activity. The candidate miRNAs were validated in 70 MsPGN patients and 70 healthy controls by quantitative real-time PCR (RT-qPCR). The specificity and sensitivity of the miRNA panel was assessed by receiver operating characteristic (ROC) curves. In addition, the candidate miRNA levels were measured in the different MsPGN progression and in the membranous nephropathy (MN) patients and the hypothetical role of the candidate miRNA on mesangial cell proliferation was analysed. Situ hybridization was performed to examine the candidate miRNA levels in the glomerulus. These results showed that miR-106a-5p and miR-30a-5p were highly expressed in MsPGN patients compared with healthy controls and could discriminate MsPGN from healthy controls with an area under the ROC curve (AUC) of 0.93. In addition, the two miRNAs were not only higher in moderate and severe MsPGN patients, but could distinguish MsPGN from MN. We also observed a decreased expression in MsPGN regression group after treatment. Plasma miR-106a-5p level was positively correlated with estimated glomerular filtration rate (eGFR). Furthermore, the two miRNAs were highly expressed in MsPGN glomerulus and their overexpression could prompt mesangial cell proliferation. Plasma miR-30a-5p and miR-106a-5p can serve as novel and potential diagnostic biomarkers for MsPGN. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have been reported to dysregulate and involve in the pathology of hepatocellular carcinoma (HCC). Nonetheless, the functional role of lncRNA T cell leukemia/lymphoma 6 (TCL6) and its underlying mechanism in HCC remain unclear. Herein, we analyzed the expression of TCL6 and elucidated its mechanistic involvement in HCC. Bioinformatics analyses indicated TCL6 was evidently downregulated in HCC tissues compared with normal controls. TCL6 was downregulated while microRNA‐106a‐5p (miR‐106a‐5p) was upregulated in HCC cell lines. Moreover, knockdown or overexpression of TCL6 significantly raised or diminished the expression level of miR‐106a‐5p in HCC cells, similar to the effect of miR‐106a‐5p on TCL6 expression. Functionally, TCL6 inhibited the proliferative, migratory, and invasive potentials of HCC cells as analyzed by cell counting kit‐8, scratch wound healing, and transwell assays, respectively. Conversely, miR‐106a‐5p exerted an opposite effect on the proliferative, migratory, and invasive potentials of HCC. RNA immune precipitation and luciferase reporter assays revealed TCL6 directly bound to miR‐106a‐5p and luciferase reporter assay verified phosphatase and tensin homolog (PTEN) was a target gene of miR‐106a‐5p. Mechanistically, TCL6 knockdown evidently reduced PTEN expression at both messenger RNA and protein levels, and miR‐106a‐5p inhibitor partially rescued this reduction effect in HCC cells. Additionally, western blot assays demonstrated miR‐106a‐5p downregulation or TCL6 overexpression promoted the protein level of PTEN, and suppressed the phosphorylation level of AKT, the protein level of phosphatidylinositol 3‐kinase (PI3K). Collectively, these results revealed TCL6 as a tumor‐suppressive lncRNA regulates PI3K/AKT signaling pathway via directly binding to miR‐106a‐5p in HCC. This mechanism provides a theoretical basis for HCC pathogenesis and a potential therapeutic strategy for HCC treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The long non-coding RNA LINC00958 acts as an oncogenic regulator in many human tumors. In this study, we aimed to investigate the role and potential molecular biological mechanisms of LINC00958 in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Aberrantly expressed LINC00958 was screened out of TCGA database. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to determine LINC00958 and miR-106a-5p expression. Cellular biological behaviors were investigated using CCK-8, colony formation, wound healing and transwell assays. Xenograft mouse models were established to determine the role of LINC00958 in HNSCC growth in vivo. The interaction between LINC00958 and miR-106a-5p was validated by Dual-Luciferase reporter gene assay. Additionally, the underlying pathways affected by LINC00958 were measured by Western blot. RESULTS: LINC00958 expression was upregulated in HNSCC tissues and cells. High LINC00958 level was correlated with the poor prognosis of HNSCC patients. Functional assays showed that the knockdown of LINC00958 inhibited HNSCC malignant phenotypes in vitro and in vivo. Mechanistically, miR-106a-5p was a potential target of LINC00958, and its expression was negatively regulated by LINC00958 in HNSCC. LINC00958 could activate AKT/mTOR signaling pathway, which was mediated by miR-106a-5p. CONCLUSIONS: Taken together, our results suggest that LINC00958 acts as an oncogenic role in HNSCC and activates AKT/mTOR signaling pathway by sponging miR-106a-5p. LINC00958 may serve as a potential target for HNSCC diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Introduction: Increasing evidence has shown that abnormally expressed long non-coding RNA (lncRNA) plays crucial roles in prostate cancer (PCa) progression. Materials and Methods: Here, we analyzed the expression level of lncRNA HAND2 antisense RNA 1 (HAND2-AS1) in PCa cells and tissues. Function assays were performed to investigate the biological roles of HAND2-AS1 in PCa cell behaviors. Bioinformatics methods, luciferase activity reporter assay, and RNA pull-down assay were performed to validate the connection of microRNA-106a-5p (miR-106a-5p) with HAND2-AS1. Also, the target of miR-106a-5p was explored using the same methods. Results: Our results revealed HAND2-AS1 expression was decreased in both PCa cells and tissues. In vitro functional assays showed HAND2-AS1 could inhibit PCa cell proliferation and colony formation through promoting cell apoptosis. Dual-luciferase activity assays showed miR-106a-5p could directly bind with HAND2-AS1 and RNA binding motif protein 24 (RBM24). Mechanistically, we showed that HAND2-AS1 regulates PCa cell behaviors via targeting miR-106a-5p/RBM24 axis. Conclusion: In summary, our results illustrated that HAND2-AS1 functions as miR-106a-5p sponge to regulate RBM24 expression, and to influence PCa progression. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the role and underlying mechanism of H19 in regulating angiogenic capacity of extravillous trophoblasts.Methods: Gain and loss of function experiments were performed using a human first-trimester extravillous trophoblast (EVT) cell line, HTR-8/SVneo cells. H19 was overexpressed or knocked down in HTR-8 cells by transfecting plasmid harboring whole-length H19 sequence (pH19) or siRNA specially targeting H19, respectively (siH19). Cell migration and tube-formation assay were assessed in the indicated groups. Gene expression was detected by RT-qPCR, Western blot, and ELISA assay.Results: Overexpression of H19 in EVT cells increased cell migration and tube formation, while downregulation of H19 in EVT cells decreased cell migration and tube formation. Furthermore, we found that H19 played its role by VEGFA. In addition, we demonstrated the H19/miR-106a-5p/VEGFA regulatory axis in EVT. Experiments of the clinical specimen showed that H19 was very abundantly expressed in human first-trimester trophoblasts, and we found that the expression of H19 and VEGFA were significantly downregulated in the villous tissues from idiopathic recurrent miscarriage (RM) patients; moreover, the expression of H19 and VEGFA was positively correlated.Conclusion: H19/miR-106a-5p/VEGFA axis plays a role in regulating the angiogenic capacity of EVT, which might contribute to idiopathic RM. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an erosive polyarthritis that can lead to severe joint destruction and painful disability if left untreated. Angiogenesis, a critical pathogenic mechanism in RA, attracts inflammatory leukocytes into the synovium, which promotes production of proinflammatory cytokines and destructive proteases. Adipokines, inflammatory mediators secreted by adipose tissue, also contribute to the pathophysiology of RA. The most abundant serum adipokine is adiponectin, which demonstrates proinflammatory effects in RA, although the mechanisms linking adiponectin and angiogenic manifestations of RA are not well understood. Our investigations with the human MH7A synovial cell line have revealed that adiponectin dose- and time-dependently increases vascular endothelial growth factor (VEGF) expression, stimulating endothelial progenitor cell (EPC) tube formation and migration. These adiponectin-induced angiogenic activities were facilitated by MEK/ERK signaling. In vivo experiments confirmed adiponectin-induced downregulation of microRNA-106a-5p (miR-106a-5p). Inhibiting adiponectin reduced joint swelling, bone destruction, and angiogenic marker expression in collagen-induced arthritis (CIA) mice. Our evidence suggests that targeting adiponectin has therapeutic potential for patients with RA. Clinical investigations are needed.

Long noncoding RNAs (lncRNAs) have emerged as important regulators of human cancers. LncRNA GAS5 (GAS5) is identified as a tumor suppressor involved in several cancers. However, the roles of GAS5 and the mechanisms responsible for its functions in gastric cancer (GC) have not been well documented. Herein, the decreased GAS5 and increased miRNA-106a-5p levels were observed in GC and cell lines. GAS5 level was significantly inversely correlated with miRNA-106a-5p level in GC tissues. Moreover, dual-luciferase reporter and qRT-PCR assays showed that GAS5 bound to miRNA-106a-5p and negatively regulated its expression in GC cells. Functional experiments showed that GAS5 overexpression suppressed GC cell proliferation, migration and invasion capabilities, and promoted apoptosis, while miRNA-106a-5p overexpression inverted the functional effects induced by GAS5 overexpression. In vivo, GAS5 overexpression inhibited tumor growth by negatively regulating miRNA-106a-5p expression. Mechanistic investigations revealed that GAS5 overexpression inactivated the Akt/mTOR pathway by suppressing miRNA-106a-5p expression in vitro and in vivo. Taken together, our findings conclude the GAS5 overexpression suppresses tumorigenesis and development of gastric cancer by sponging miR-106a-5p through the Akt/mTOR pathway.

Background: Luteolin, a common dietary flavonoid found in plants, has been shown to have anti-cancer properties. However, its exact mechanisms of action in non-small cell lung cancer (NSCLC) are still not fully understood, particularly its role in regulating broader genomic networks and specific gene targets. In this study, we aimed to elucidate the role of microRNAs (miRNAs) in NSCLC treated with luteolin, using A549 cells as a model system., Materials and Methods: miRNA profiling was conducted on luteolin-treated A549 cells using Exiqon microarrays, with validation of selected miRNAs by qRT-PCR. Bioinformatic analysis identified the regulatory roles of miRNAs in biological processes and pathways following luteolin treatment. Computational algorithms were employed to identify potential target genes. A549 cells were transfected with miR-106a-5p mimic and inhibitor or their corresponding controls. The expression levels of 2 genes, twist basic helix-loop-helix transcription factor 1 (TWIST1) and matrix metallopeptidase 2 (MMP2), and cell migration were assessed., Results: miRNA profiling identified 341 miRNAs, with 18 exhibiting significantly altered expression ( P  < 0.05). Subsequent qRT-PCR analysis confirmed altered expression of 6 selected miRNAs. KEGG and GO analyses revealed significant alterations in pathways and biological processes crucial for tumor biology. TWIST1 and MMP2, which both contain conserved miR-106a-5p binding sites, exhibited an inverse correlation with the expression levels of miR-106a-5p. Dual-luciferase reporter assays confirmed TWIST1 and MMP2 as direct targets of miR-106a-5p. Luteolin treatment led to a reduction in A549 cell migration, and this reduction was further amplified by the overexpression of miR-106a-5p., Conclusion: Luteolin inhibits A549 cell migration by modulating the miRNA landscape, shedding light on its mechanisms and laying the foundation for miRNA-based therapeutic approaches for NSCLC., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Periodontal ligament stem cells (PDLSCs) are characterized by multiple differentiation potential and potent self‐renewal ability, yet much remains to be elucidated that what determines these properties. Long noncoding RNAs (lncRNAs) have been suggested to involve in multiple biological process under physiological and pathological conditions, including osteogenic differentiation. In the present study, we performed comprehensive lncRNA profiling by lncRNA microarray analysis and identified prostate cancer‐associated ncRNA transcript‐1 (lncPCAT1) was gradually increased in PDLSCs during consecutive osteogenic induction, and it could further positively regulate the osteogenic differentiation both in vitro and in vivo, whereas lncPCAT1 inhibition led to suppressed osteogenic differentiation. Thereafter, we inferred a predicted interaction between lncPCAT1 and miR‐106a‐5p and then confirmed the direct binding sites of miR‐106a‐5p on lncPCAT1. Although miR‐106a‐5p upregulation led to decreased osteogenic differentiation, lncPCAT1 overexpression could reverse its suppression, indicating that lncPCAT1 act as a competing endogenous RNA for miR‐106a‐5p. Moreover, lncPCAT1 could sponge miR‐106a‐5p to upregulate miR‐106a‐5p‐targeted gene BMP2, which was a crucial gene involved in osteogenic differentiation. Interestingly, we found that E2F5, another target of miR‐106a‐5p, could bind to the promoter of lncPCAT1 and then form a feed‐forward regulatory network targeting BMP2. In conclusion, our study provided a novel lncRNA‐miRNA feed‐forward regulatory network and a promising target to modulate the osteogenic differentiation of PDLSCs. [ABSTRACT FROM AUTHOR]

Objective(s): Multiple sclerosis (MS) is considered as a chronic type of an inflammatory disease characterized by loss of myelin of CNS. Recent evidence indicates that Interleukin 17 (IL-17)- producing T helper cells (Th17 cells) population are increased and regulatory T cells (Treg cells) are decreased in MS. Despite extensive research in understanding the mechanism of Th17 and Treg differentiation, the role of microRNAs in MS is not completely understood. Thereby, as a step closer, we analyzed the expression profile of miR-9-5p and miR-106a-5p, and protein level of retinoic acid receptor (RAR)-related orphan receptor C (RORC; Th17 master transcription factor) as direct target of miR-106a-5p and forkhead box P3 (FOXP3; Treg master transcription factor) as indirect target of miR- 9-5p in CD4+ T cells in two groups of relapsing and remitting in our relapsing-remitting MS (RR-MS) patients. Materials and Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to assess the expression of miRNAs and mRNAs, in 40 RR-MS patients and 11 healthy individuals. Thus, FOXP3 and RAR-related orphan receptor κt (RORκt) was assessed in CD4+T-cells by flow cytometry. We also investigated the role of these miRNAs in Th17/Treg differentiation pathway through bioinformatics tools. Results: An up-regulation of miR-9-5p and down-regulation of miR-106a-5p in relapsing phase of MS patients were observed compared to healthy controls. RORC and FOXP3 were up-regulated in relapsing and remitting phases of MS, respectively. Conclusion: Expression pattern of miR-9-5p and miR-106a-5p and their targets suggest a possible inducing role of miR-9-5p and suppressing role of miR-106a-5p in differentiation pathway of Th17 cells during MS pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: lncRNA H19 has been considered as an oncogenic lncRNA in many human tumours. In the present study, we identify the role and molecular mechanism of lncRNA H19 in melanoma.Method: QRT-PCR was used to detect the expression of lncRNA H19 and E2F3 was detected in melanoma tissues. Cell counting kit-8 (CCK8), representative metabolites analysis was used to explore the biological function of lncRNA H19, miR-106a-5p and E2F3 in melanoma cells. Bioinformatics, luciferase reporter assays, MS2-RIP and RNA pull-down assay was used to demonstrate the molecular mechanism of lncRNA H19 in melanoma. We further test the function of lncRNA H19 in vivo though Xenograft tumour assay.Results: We found that lncRNA H19 was increased in melanoma tissue, and lncRNA H19 was correlated with poor prognosis of melanoma patients. miR-106a-5p acts as a tumour suppressor in melanoma by targeting E2F3. E2F3 affects the melanoma cell glucose metabolism and growth. We also demonstrated that lncRNA H19 may function as the sponge of miR-106a-5p to up-regulate E2F3 expression, and consequently promote the glucose metabolism and growth of melanoma.Conclusions: This result elucidates a new mechanism for lncRNA H19 in melanoma development and provides a survival indicator and potential therapeutic target for melanoma patients. [ABSTRACT FROM AUTHOR]

Previous study has identified the aberrant expression of LINC00657, a long non-coding RNA (lncRNA), in human breast cancer. However, the expression pattern, biological function and underlying mechanism of LINC00657 in human hepatocellular carcinoma (HCC) remain obscure. The expression levels of LINC00657 in HCC tissues and cell lines were determined by quantitative real-time PCR. CCK-8 assay, cell colony formation assay, cell cycle analysis, Transwell assay were performed to determine whether LINC00657 could affect HCC progression. Luciferase reporter assay was used to assess the target of LINC00657. Expressions of the relevant proteins were analyzed by Western blot. Herein, we found that LINC00657 was downregulated in HCC tissue specimens as well as in malignant HCC cell lines. LINC00657 overexpression inhibited the proliferation, migration and invasion of HCC cells, while LINC00657 depletion promoted both cell viability and cell invasion in vitro . We also found that LINC00657 could inhibit tumor growth in vivo . Further experiments demonstrated that down-regulated LINC00657 increased the expression of miR-106a-5p. miR-106a-5p decreased the abundances of PTEN protein, while had no impact on PTEN mRNA. Moreover, we identified that both LINC00657 and PTEN mRNA were targets of miR-106a-5p by using dual-luciferase reporter assay. Our results provide the new evidence supporting the tumor-suppressive role of LINC00657 in HCC, suggesting that LINC00657 might play a role in HCC and can be a novel therapeutic target for treating HCC. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are aberrantly expressed in various cancers. Fer-1-like protein 4 (FER1L4), one of lncRNAs, plays a role as tumor suppressor in various human cancers and can be regulated by microRNA. However, the role and function of FER1L4 in human hepatocellular carcinoma (HCC) remains unknown. The aim of the present study was to annotate the role of FER1L4 and its clinical value in HCC. In the present study, we found that FER1L4 was lowly expressed in HCC tissue specimens as well as in malignant HCC cell lines, while the situation is opposite in miR-106a-5p. We found that down-regulated FER1L4 increased the expression of miR-106a-5p significantly and there was a reciprocal repression between FER1L4 and miR-106a-5p. Moreover, we identified FER1L4 as a target of miR-106a-5p by using dual-luciferase reporter assay. Knockdown of FER1L4 promoted the malignancy of HCC cells, including proliferation, migration, and invasion, and inhibited cell apoptosis. We also found that FER1L4 functions as a tumor suppressor in vivo. Together, these results suggest that FER1L4 could exert a tumor suppressive impact on HCC, which at least, in part, through suppressing miR-106a-5p expression. FER1L4, as well as miR-106a-5p, can predict the clinical prognosis of HCC alone or combined, which may be a novel therapeutic target for treating HCC. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a common malignant cancer in elderly males in Western countries. Whole-genome sequencing confirmed that long non-coding RNAs (lncRNAs) are frequently altered in castration-resistant prostate cancer (CRPC) and promote drug resistance to cancer therapy. Therefore, elucidating the prospective role of lncRNAs in PCa oncogenesis and progression is of remarkable clinical significance. In this study, gene expression in prostate tissues was determined using RNA-sequencing datasets, and the gene diagnostic and prognostic values of CRPC were analyzed using bioinformatics. Further, the expression levels and clinical significance of MAGI2 Antisense RNA 3 (MAGI2-AS3) in PCa clinical specimens were evaluated. The tumor-suppressive activity of MAGI2-AS3 was functionally explored in PCa cell lines and animal xenograft models. MAGI2-AS3 was found to be aberrantly decreased in CRPC and was negatively correlated with Gleason score and lymph node status. Notably, low MAGI2-AS3 expression positively correlated with poorer survival in patients with PCa. The overexpression of MAGI2-AS3 significantly inhibited the proliferation and migration of PCa in vitro and in vivo. Mechanistically, MAGI2-AS3 could play a tumor suppressor function in CRPC through a novel miR-106a-5p/RAB31 regulatory network and could be a target for future cancer therapy. • It is the first report on MAGI2-AS3/miR-106a-5p/RAB31 axis in CRPC. • Decreased MAGI2-AS3 and RAB31 expressions were found in CRPC. • Reduced MAGI2-AS3 suppresses the proliferation and migration of PCa. • MAGI2-AS3 competitively binds with miR-106a-5p to regulate the expression of RAB31. [ABSTRACT FROM AUTHOR]