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Abstract: Human cholesteatoma perimatrix fibroblasts (hCPFs) can stimulate the endothelial cells of nearby microvessels to proliferate and migrate in a paracrine manner. Exosomes, secreted from various cell types, are one of the most important paracrine factors and play critical roles in intercellular communication. However, whether exosomes derived from human cholesteatoma perimatrix fibroblasts (hCPFs‐Exo) can promote angiogenesis has not been reported. In this study, we isolated exosomes secreted by hCPFs and observed that hCPFs‐Exo was able to promote migration and tube formation in human umbilical vein endothelial cells (HUVECs). Advanced studies revealed hCPFs‐Exo with low expression of miR‐106b‐5p was transferred into HUVECs, and decreased expression of miR‐106b‐5p could promote angiogenesis by targeting Angiopoietin 2 (Angpt2) via binding to its 3′‐UTR. Furthermore, low levels of miR‐106b‐5p triggered overexpression of Angpt2, and significantly increased HUVEC migration and tube formation. Taken together, our results suggest that hCPFs‐Exo transports low expressed exosomal miR‐106b‐5p to endothelial cells and promotes angiogenesis by overexpression of Angpt2. [ABSTRACT FROM AUTHOR]

Background: Although miR-106b-5p has been reported to play a pivotal role in various human malignancies, its role in colorectal cancer (CRC) remains unknown. In this study, we comprehensively investigated miR-106b-5p expression and biologic functions in CRC and the molecular mechanism involved. Patients and methods: miR-106b-5p expression was detected in CRC tissues and cell lines by quantitative reverse transcription-polymerase chain reaction. The effects of miR-106b-5p on metastasis were determined in vitro using transwell assays, and in vivo effects were evaluated using a mouse tail vein injection model. Downstream targets of miR-106b-5p were confirmed using bioinformatics programs, luciferase assays, and rescue experiments. Target gene expression and clinicopathologic parameters were also analyzed. Results: miR-106b-5p expression was lower in CRC tissues than in corresponding nontumorous tissues (P=0.009), and miR-106b-5p downregulation was negatively associated with lymph node metastasis (P=0.006). Functional assays demonstrated that miR-106b-5p overexpression suppressed CRC cell migration and invasion in vitro and lung metastasis formation in vivo. In addition, luciferase assays confirmed that miR-106b-5p directly bound to the 3' untranslated region of cathepsin A (CTSA) and that miR-106b-5p suppressed CRC cell migration and invasion by targeting CTSA. Clinicopathologic analysis showed that CTSA was significantly upregulated in CRC, and increased CTSA was negatively associated with lymph node metastasis (P=0.012). Conclusion: Our findings revealed that miR-106b-5p inhibits CRC metastasis by upregulating CTSA expression, which may lead to novel therapeutic strategies for CRC patients. [ABSTRACT FROM AUTHOR]

We previously observed that microRNA miR-106b-5p significantly increased in serum of patients with acute ischemic stroke. The present study was to determine whether miR-106b-5p antagomir can protect against cerebral ischemia/reperfusion (I/R) injury and elucidate its underlying mechanisms. Middle cerebral artery occlusion (MCAO) was operated on male Sprague Dawley rats. MiR-106b-5p antagomir significantly decreased neurological deficit scores, infarct volumes, and neuronal injury. Furthermore, miR-106b-5p antagomir markedly reduced malondialdehyde (MDA) content, restored superoxide dismutase (SOD) activity, increased the expression of myeloid cell leukemia-1 (Mcl-1) and B cell lymphoma-2 (Bcl-2), and decreased the expression of Bax in the ischemic cortex. In PC12 cells, miR-106b-5p inhibitor increased the Mcl-1 and Bcl-2 expression, which provided protection against glutamate-induced apoptosis and oxidative damage, as evidenced by decreased lactate dehydrogenase (LDH) release, and enhanced SOD activity. Notably, luciferase reported assay proved Mcl-1 was the target gene of miR-106b-5p. In conclusion, our data indicates that the neuroprotective effects of miR-106b-5p antagomir on cerebral I/R injury are associated with its inhibition of apoptosis and oxidative stress, suggesting a potential therapeutic target for ischemic stroke. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) exhibit strong self-renewal capability to contribute to tumorigenesis in lung adenocarcinoma (LUAD). N6-methyladenosine (m6A) methylation is confirmed as a key mechanism for stemness acquisition and tumor growth. Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) is a known m6A reader and is reported to participate in LUAD progression, but its relation with stemness of LUAD cells is unknown. Thus, this study aimed to uncover the effect of HNRNPA2B1 in stemness of LUAD cells. The association of HNRNPA2B1 with LUAD prognosis was analyzed via Gene Expression Profiling Interactive Analysis (GEPIA). Sphere formation, cytometry flow analysis and western blot of stemness-related genes were performed to examine the stemness of LUAD cells. m6A modification was investigated by RNA immunoprecipitation. Results depicted that HNRNPA2B1 was upregulated in LUAD CSCs. HNRNPA2B1 knockdown repressed cell stemness, proliferation, migration, and tumor growth of LUAD. As to mechanism, HNRNPA2B1 read the m6A site on primary microRNA-106b (pri-miR-106b) to facilitate the maturing of miR-106b-5p, so that miR-106b-5p targeted secreted frizzled-related protein 2 (SFRP2), activating Wnt/β-catenin signaling. In conclusion, HNRNPA2B1 inhibits SFRP2 and activates Wnt-β/catenin via m6A-mediated maturing of miR-106b-5p to aggravate stemness and LUAD progression, which potentially offered HNRNPA2B1 as a potential marker in CSCs-targeted treatment for LUAD. [Display omitted] [ABSTRACT FROM AUTHOR]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. The journal was contacted by the corresponding author to claim that they were not aware of the submission of the article, do not own the email address listed by the paper, and did not participate in the study. When contacted by the journal, the co-authors Shan Liu and Haiying Ren also denied that they participated in the study and that they were aware of the article. The co-authors Fen Hu, Yonglian Wang and Xueqing Wu did not respond to the journal's request for clarifications. The uncertainty about the identity of the author who submitted the article also cast doubt on the data and the Editor decided to retract the paper., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To study the expression level of plasma miR-106b-5p in primary immune thrombocytopenia (ITP) and its correlation with the levels of T helper 17 cell (Th17) and regulatory T cell (Treg) and the Th17/Treg ratio., Methods: A total of 79 children with ITP (ITP group) and 40 healthy children (control group) were selected as subjects. According to the treatment response, the 79 children with ITP were divided into three groups: complete response ( n =40), partial response ( n =18), and non-response ( n =21). Quantitative real-time PCR was used to measure the expression level of miR-106b-5p. Flow cytometry was used to measure the frequencies of Th17 and Treg, and the Th17/Treg ratio was calculated. The correlation of the expression level of plasma miR-106b-5p with the frequencies of Th17 and Treg and the Th17/Treg ratio was analyzed., Results: Compared with the control group, the ITP group had significantly higher levels of miR-106b-5p, Th17, and Th17/Treg ratio ( P <0.05) and a significantly lower level of Treg ( P <0.05). After treatment, the ITP group had significant reductions in the levels of miR-106b-5p, Th17, and Th17/Treg ratio ( P <0.05) and a significant increase in the level of Treg ( P <0.05). Compared with the partial response and non-response groups, the complete response group had significantly lower levels of miR-106b-5p, Th17, and Th17/Treg ratio ( P <0.05) and a significantly higher level of Treg ( P <0.05). The correlation analysis showed that in the children with ITP, the expression level of plasma miR-106b-5p was positively correlated with the Th17 level and the Th17/Treg ratio ( r =0.730 and 0.816 respectively; P <0.001) and was negatively correlated with the Treg level ( r =-0.774, P <0.001)., Conclusions: A higher expression level of miR-106b-5p and Th17/Treg imbalance may be observed in children with ITP. The measurement of miR-106b-5p, Th17, Treg, and Th17/Treg ratio during treatment may be useful to the evaluation of treatment outcome in children with ITP.

• Baicalin attenuates oral squamous cell carcinoma by inhibiting microRNA-106b-5p. • Disabled homolog 2 is a target of microRNA-106b-5p. • Baicalin inactivates Wnt/β-catenin pathway by upregulating disabled homolog 2. • MicroRNA-106b-5p promotes oral squamous cell carcinoma by disabled homolog 2. The aim of this study was to investigate the role and molecular regulatory mechanisms of baicalin in oral squamous cell carcinoma (OSCC) progression. Gene expression in OSCC cells was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). OSCC cell viability, migration, invasion and stemness were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2′-deoxyuridine (EdU), wound healing, Transwell, and sphere formation assays. The target genes of miR-106b-5p were predicted using bioinformatic tools. The interaction between microRNA-miR-106b-5p (miR-106b-5p) and disabled homolog 2 (DAB2) was confirmed by a luciferase reporter assay. TOP/FOP-Flash reporter assay and western blot analysis were used to analyze the activity of the Wnt/β-catenin pathway. Baicalin inhibited OSCC cell viability, migration, invasion, and stemness. Baicalin downregulated miR-106b-5p expression. In addition, MiR-106b-5p upregulation reversed the effects of baicalin on OSCC cells. As a target gene of miR-106b-5p, DAB2 was negatively regulated by miR-106b-5p and upregulated by baicalin in OSCC cells. MiR-106b-5p activated Wnt/β-catenin pathway in OSCC cells by inhibiting DAB2. Baicalin suppressed Wnt/β-catenin pathway by upregulating DAB2. In rescue assays, miR-106b-5p overexpression-induced promotion of OSCC cellular processes was attenuated by DAB2 upregulation. Baicalin exerts anti-tumor effects in OSCC by inhibiting the miR-106b-5p-Wnt/β-catenin pathway via upregulating DAB2. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs), which generally act as microRNA (miRNA) sponges to competitively regulate the downstream target genes of miRNA, play an essential role in cancer biology. However, few studies have been reported on the role of circRNA based competitive endogenous RNA (ceRNA) network in hepatocellular carcinoma (HCC). Herein, we aimed to screen and establish the circRNA/miRNA/mRNA networks related to the prognosis and progression of HCC and further explore the underlying mechanisms of tumorigenesis. Methods: GEO datasets GSE97332, GSE108724, and GSE101728 were utilized to screen the differentially expressed circRNAs (DE-circRNAs), DE-miRNAs, and DEmRNAs between HCC and matched para-carcinoma tissues. After six RNA-RNA predictions and five intersections between DE-RNAs and predicted RNAs, the survival-related RNAs were screened by the ENCORI analysis tool. The ceRNA networks were constructed using Cytoscape software, based on two models of up-regulated circRNA/down-regulated miRNA/up-regulated mRNA and down-regulated circRNA/up-regulated miRNA/down-regulated mRNA. The qRT-PCR assay was utilized for detecting the RNA expression levels in HCC cells and tissues. The apoptosis, Edu, wound healing, and transwell assays were performed to evaluate the effect of miR-106b-5p productions on the proliferation, invasion, and metastasis of HCC cells. In addition, the clone formation, cell cycle, and nude mice xenograft tumor assays were used to investigate the influence of hsa&#95;circ&#95;0001495 (circCCNB1) silencing and overexpression on the proliferation of HCC cells in vitro and in vivo . Furthermore, the mechanism of downstream gene DYNC1I1 and AKT/ERK signaling pathway via the circCCNB1/miR-106b-5p/GPM6A network in regulating the cell cycle was also explored. Results: Twenty DE-circRNAs with a genomic length less than 2000bp, 11 survival-related DE-miRNAs, and 61 survival-related DE-mRNAs were screened out and used to construct five HCC related ceRNA networks. Then, the circCCNB1/miR-106b-5p/GPM6A network was randomly selected for subsequent experimental verification and mechanism exploration at in vitro and in vivo levels. The expression of circCCNB1 and GPM6A were significantly down-regulated in HCC cells and cancer tissues, while miR-106b-5p expression was up-regulated. After transfections, miR-106b-5p mimics notably enhanced the proliferation, invasion, and metastasis of HCC cells, while the opposite was seen with miR-105b-5p inhibitor. In addition, circCCNB1 silencing promoted the clone formation ability, the cell cycle G1-S transition, and the growth of xenograft tumors of HCC cells via GPM6A downregulation. Subsequently, under-expression of GPM6A increased DYNC1I1 expression and activated the phosphorylation of the AKT/ERK pathway to regulate the HCC cell cycle. Conclusions: We demonstrated that circCCNB1 silencing promoted cell proliferation and metastasis of HCC cells by weakening sponging of oncogenic miR-106b-5p to induce GPM6A underexpression. DYNC1I1 gene expression was up-regulated and further led to activation of the AKT/ERK signaling pathway., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Intracerebral hemorrhage (ICH) is one of the most common refractory diseases. Long non-coding RNAs (lncRNAs) play crucial roles in ICH. This study was designed to investigate the role of lncRNA H19 in ICH and the underlying molecular mechanisms involved. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to determine mRNA expression. Cell viability was analyzed using Cell Counting Kit 8 (CCK8). PI staining Flow cytometry and TdT-mediated biotinylated nick end-labeling (TUNEL) assays were performed to determine ferroptosis in brain microvascular endothelial cells (BMVECs). Targeting relationships were predicted using Starbase and TargetScan and verified by RNA pull-down and luciferase reporter gene assays. Western blotting was performed to assess protein expression. LncRNA H19 is highly expressed in ICH model cells. Over-expression of H19 suppressed cell viability and promoted ferroptosis of BMVECs. miR-106b-5p is predicted to be a target of H19. The expression of miR-106b-5p was lower in oxygen and glucose deprivation hemin-treated (OGD/H-treated) cells. Over-expression of miR-106b-5p reversed the effects of H19 on cell viability and ferroptosis in BMVECs. Furthermore, acyl-CoA synthetase long-chain family member 4 ( ACSL4 ) was verified to be a target gene of miR-106b-5p and was highly expressed in OGD/H-treated cells. Upregulation of ACSL4 inhibited the effects of miR-106b-5p and induced BMVEC dysfunction. In conclusion, lncRNA H19 was overexpressed in ICH. Knockdown of H19 promoted cell proliferation and suppressed BMVECs ferroptosis by regulating the miR-106b-5p/ACSL4 axis. Therefore, H19 knockdown may be a promising therapeutic strategy for ICH.

Long non-coding RNAs (lncRNAs) play important regulatory roles in hepatocellular carcinoma (HCC). However, the function of LOC107985656 in HCC progression remains unclear. The lncRNA, mRNA and miRNA levels in HCC tissues or cells were measured using real-time quantitative polymerase chain reaction (RT-qPCR). The proliferation of cancer cells was evaluated using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) viability and colony formation assays. Bioinformatics prediction, dual luciferase assay and RNA pull-down assay were performed to analyze the relationships between LOC107985656 and miR-106b-5p, or miR-106b-5p and large tumor suppressor 1 (LATS1). The protein expression levels were detected using Western blot. Results showed that LncRNA LOC107985656 was downregulated in HCC tissues and cells. Upregulation of LOC107985656 inhibited the proliferation of HCC cells, whereas its knockdown promoted this phenomenon. LOC107985656 could activate the tumor-suppressive Hippo pathway by repressing yes association protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ) (two homologs of Yki) protein expression in HCC. Further investigation suggested that LOC107985656 regulated the expression of LATS1 by acting as a sponge for absorbing miR-106b-5p in HCC cells. In conclusion, this study unraveled the role of LOC107985656 following a ceRNA (competing endogenous RNAs) mechanism for the miR-106b-5p/LATS1 axis in HCC. The results indicate potential diagnostic and therapeutic applications of LOC107985656 in HCC. Abbreviations: HCC: hepatocellular carcinoma; LncRNA: long non-coding RNA; LATS1: large tumor suppressor 1; MTT: 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide; YAP: yes association protein; WWTR1: WW domain-containing transcription regulator protein 1; cDNA: single-stranded complementary DNA; RT-qPCR: real-time quantitative polymerase chain reaction; Radio-Immunoprecipitation Assay (RIPA); BCA: bicinchoninic acid; ASO: antisense oligonucleotide; MST1/2: Ste20-like kinases 1/2; TEAD: TEA domain transcription factor; ceRNA: competing endogenous RNAs.

Recently, circular RNAs (circRNAs) have become an intense focus of research and large numbers of circRNAs have been identified, awaiting functional elucidation. Thus, the present study aims to examine the regulation of circRNAs and its molecular mechanism in lung cancer growth. Here, we show that circular RNA circ&#95;0000677 was overexpressed and correlated with poor prognosis in non-small cell lung cancer (NSCLC) patients. Functionally, circ&#95;0000677 knockdown markedly inhibited proliferation of NSCLC cells by observing of immunofluorescence staining of Ki67, clone formation assay, and xenograft experiments. In mechanism, circ&#95;0000677 acted as a sponge of microRNA-106b and further regulated CCDND1 gene expression in NSCLC cells by dual luciferase activity assay and their expression examination. Taken together, these findings suggest a role for circ&#95;0000677/miR-106b/CCND1 regulation axis in promoting NSCLC growth and progression.

Acute renal injury (ARI) is a life‑threatening condition and a main contributor to end‑stage renal disease, which is mainly caused by ischemia‑reperfusion (I/R). miR‑106b‑5p is a kidney function‑related miRNA; however, whether miR‑106b‑5p regulates the progression of ARI remains unclear. The present study thus aimed to examine the effects of miR‑106b‑5p antagonist on the regulation of ARI progression. It was found that miR‑106b‑5p expression was upregulated in the renal tissue of rats with I/R‑induced ARI and in NRK‑52E rat renal proximal tubular epithelial cells subjected to hypoxia‑reoxygenation (H/R). In vitro , H/R induction suppressed the proliferation, and promoted the apoptosis and autophagy of NRK‑52E cells, whereas miR‑106b‑5p antagonist (inhibition of miR‑106b‑5p) promoted the proliferation, and attenuated the apoptosis and autophagy of NRK‑52E cells under the H/R condition. Dual luciferase reporter gene assay validated that transcription factor 4 (TCF4) was a target of miR‑106b‑5p. It was further found that TCF4 overexpression promoted the proliferation, and inhibited the apoptosis and autophagy of NRK‑52E cells subjected to H/R. Moreover, the effects of miR‑106b‑5p antagonist on NRK‑52E cell proliferation, apoptosis and autophagy were mediated through the regulation of TCF4. In vivo , miR‑106b‑5p antagonist reduced the severity of renal injury, decreased cell proliferation in renal tissues and lowered the serum creatinine (Scr) and blood urea nitrogen (BUN) levels in the blood samples from rats with I/R‑induced ARI. On the whole, the findings presented herein demonstrate that miR‑106b‑5p antagonist attenuates ARI by promoting the proliferation, and suppressing the apoptosis and autophagy of renal cells via upregulating TCF4.

Temporal lobe epilepsy (TLE) is the most prevalent form of acquired epilepsy. Circular RNAs (circRNAs) have recently been highlighted as important regulators in TLE. Nevertheless, the role and mechanism of circRNA Drosha ribonuclease III (circ_DROSHA) in TLE pathogenesis are still unknown. Magnesium-free extracellular solution was used to establish the TLE cell model. The levels of circ_DROSHA, myocyte-specific enhancer factor 2C (MEF2C) and miR-106b-5p were determined by qRT-PCR and western blot. Cell proliferation was detected by the Cell Counting-8 Kit (CCK-8) assay, and cell apoptosis was measured by flow cytometry. Targeted relationships among circ_DROSHA, miR-106b-5p and MEF2C were confirmed by a dual-luciferase reporter or RNA immunoprecipitation (RIP) assay. Our data showed that circ_DROSHA was down-regulated in the serum samples of TLE patients and the TLE cell model. Circ_DROSHA up-regulation alleviated the cytotoxicity of the TLE cell model by enhancing cell proliferation and repressing cell apoptosis. Circ_DROSHA directly bound to miR-106b-5p. Moreover, miR-106b-5p represented a downstream effector of circ_DROSHA function. MEF2C was a direct target of miR-106b-5p, and miR-106b-5p knockdown relieved magnesium-free treatment-induced cell injury by up-regulating MEF2C. Furthermore, circ_DROSHA regulated MEF2C expression via sponging miR-106b-5p. Our study suggested that the enforced expression of circ_DROSHA alleviated the cell damage of the TLE cell model at least in part through the regulation of the miR-106b-5p/MEF2C axis. • Circ_DROSHA functioned as a molecular sponge of miR-106b-5p. • SOX7 was directly target by miR-106b-5p. • Circ_DROSHA regulated the injury of the TLE cell model by the miR-106b-5p/SOX7 axis. [ABSTRACT FROM AUTHOR]

Background: Although cardiovascular imaging techniques are widely used to diagnose myocardial ischemia in patients with suspected stable coronary artery disease (CAD), they have limitations related to lack of specificity, sensitivity and "late" diagnosis. Additionally, the absence of a simple laboratory test that can detect myocardial ischemia in CAD patients, has led to many patients being first diagnosed at the time of the development of myocardial infarction. Nourin is an early blood-based biomarker rapidly released within five minutes by "reversible" ischemic myocardium before progressing to necrosis. Recently, we demonstrated that the Nourin-dependent miR-137 (marker of cell damage) and miR-106b-5p (marker of inflammation) can diagnose myocardial ischemia in patients with unstable angina (UA) and also stratify severity of ischemia, with higher expression in acute ST-segment elevation myocardial infarction (STEMI) patients compared to UA patients. Minimal baseline-gene expression levels of Nourin miRNAs were detected in healthy subjects. Objectives: To determine: (1) whether Nourin miRNAs are elevated in chest pain patients with myocardial ischemia suspected of CAD, who also underwent dobutamine stress echocardiography (DSE) or ECG/Treadmill stress test, and (2) whether the elevated levels of serum Nourin miRNAs correlate with results of ECHO/ECG stress test in diagnosing CAD patients. Methods: Serum gene expression levels of miR-137, miR-106b-5p and their corresponding molecular pathway network were measured blindly in 70 enrolled subjects using quantitative real time PCR (qPCR). Blood samples were collected from: (1) patients with chest pain suspected of myocardial ischemia (n = 38) both immediately "pre-stress test" and "post-stress test" 30 min. after test termination; (2) patients with acute STEMI (n = 16) functioned as our positive control; and (3) healthy volunteers (n = 16) who, also, exercised on ECG/Treadmill stress test for Nourin baseline-gene expression levels. Results: (1) strong correlation was observed between Nourin miRNAs serum expression levels and results obtained from ECHO/ECG stress test in diagnosing myocardial ischemia in CAD patients; (2) positive "post-stress test" patients with CAD diagnosis showed upregulation of miR-137 by 572-fold and miR-106b-5p by 122-fold, when compared to negative "post-stress test" patients (p < 0.001); (3) similarly, positive "pre-stress test" CAD patients showed upregulation of miR-137 by 1198-fold and miR-106b-5p by 114-fold, when compared to negative "pre-stress test" patients (p < 0.001); and (4) healthy subjects had minimal baseline-gene expressions of Nourin miRNAs. Conclusions: Nourin-dependent miR-137 and miR-106b-5p are promising novel blood-based biomarkers for early diagnosis of myocardial ischemia in chest pain patients suspected of CAD in outpatient clinics. Early identification of CAD patients, while patients are in the stable state before progressing to infarction, is key to providing crucial diagnostic steps and therapy to limit adverse cardiac events, improve patients' health outcome and save lives. [ABSTRACT FROM AUTHOR]

• Matrine alleviates cardiac dysfunction and inflammatory responses in sepsis mice. • Matrine promotes the viability and inhibits the inflammation of H9C2 cells. • Matrine regulates the PTENP1/miR-106b-5p axis both in vitro and in vivo. • The PTENP1/miR-106b-5p axis mediates the cardioprotective effects of matrine. Matrine has attractive cardioprotective effects in some diseases. This study aimed to evaluate the therapeutic potential of matrine against cardiac dysfunction induced by sepsis in vivo and in vitro , and further explore the related mechanisms. Cecal ligation and puncture (CLP) was used to induce a sepsis mice model, and H9C2 cells treated with lipopolysaccharide (LPS) were used as a cardiac myoblast injury model. The evaluation of cardiac function of mice was performed by measuring cardiac function biomarker levels and hemodynamic indicators. An ELISA method was used to examine inflammatory cytokine levels. H9C2 cell viability was measured using MTT assay. The expression of non-coding RNAs that might be involved in matrine function was analyzed using real-time quantitative PCR. Matrine could significantly improve the cardiac function and attenuate the inflammatory response of the mice model, and could increase H9C2 viability and inhibit inflammation in the cell model. By matrine administration, the expression of PTENP1 was downregulated, but miR-106b-5p expression was upregulated both in vivo and in vitro. The cardioprotective effects of matrine in mice and cell models could be reversed by the overexpression of PTENP1 or the knockdown of miR-106b-5p, and the overexpression of miR-106b-5p could significantly abolish the effects of PTENP1 on cardiac function and inflammation. All the data revealed that matrine can alleviate sepsis-related cardiac dysfunction by enhancing cardiac myoblast viability and attenuating inflammatory responses through the PTENP1/miR-106b-5p axis. [ABSTRACT FROM AUTHOR]

In this study, we investigated the mechanistic role and prognostic significance of IGSF10 in lung adenocarcinoma. Oncomine database analysis showed that IGSF10 expression was significantly reduced in most cancer types, including lung adenocarcinoma (LUAD). In the TCGA-LUAD dataset, IGSF10 expression correlated positively with proportions of tumor-infiltrated B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells. Kaplan-Meier survival analysis showed that overall survival of patients with low IGSF10 expression was significantly shorter than those with high IGSF10 expression. MiRWalk2.0 database analysis and dual luciferase reporter assays confirmed that miR-106b-5p suppressed IGSF10 expression by binding to its 3'UTR. MiR-106b-5p levels inversely correlated with IGSF10 expression in the TCGA-LUAD dataset. Moreover, inhibition of miR-106b-5p significantly decreased in vitro proliferation, migration, and invasion by LUAD cells, whereas miR-106b-5p overexpression reversed those effects. These results demonstrate that IGSF10 is an independent prognostic factor for LUAD. Furthermore, miR-106b-5p suppressed IGSF10 expression in LUAD tissues by binding to its 3'UTR, which makes IGSF10 and miR-106b-5p potential prognostic biomarkers and therapeutic targets in LUAD patients.

Long non-coding RNA (LncRNA) involved in types of physiological insults and diseases via regulating the responses of complex molecular, including cerebral ischemia-reperfusion (I/R) injury. LncRNA SNHG16 played a potential role in ketamine-induced neurotoxicity. In this study, we utilized an in vitro cell model of I/R to examine the specific function and mechanism of LncRNA SNHG16 in oxygen-glucose deprivation and reperfusion (OGD/R) induced SH-SY5Y cells. After in vitro treatment of OGD/R, the lower the SH-SY5Y cell survival, the higher cell the apoptosis and increased caspase-3 activity was observed. Also, OGD/R induced endoplasmic reticulum stress (ERS) through increasing GRP78 and CHOP expressions and down-regulated LncRNA SNHG16 in SH-SY5Y cells. Conversely, LncRNA SNHG16 overexpression promoted OGD/R induced SH-SY5Y cell survival, suppressed its apoptosis, and caspase-3 activity. GRP78 and CHOP expressions were significantly suppressed in LncRNA SNHG16 overexpressing cells. MiR-106b-5p expression was increased and LIMK1 expression was down-regulated in OGD/R induced SH-SY5Y cells, and these effects were reversed by LncRNA SNHG16 overexpression, respectively. Moreover, LIMK1 is a direct target of MiR-106b-5p, and knockdown of LIMK1 reversed the effects of LncRNA SNHG16 on OGD/R-induced SH-SY5Y cells biology. Altogether, these results confirmed an important neuroprotection role of LncRNA SNHG16 in OGD/R induced SH-SY5Y cells injury, and miR-106b-5p/LIMK1 signal axis was involved in the action of LncRNA SNHG16. [ABSTRACT FROM AUTHOR]

Previous studies reported perturbed expressing of X-linked inhibitor of apoptosis protein (XIAP) under lead (Pb) exposure. However, researches on XIAP expression mainly focused on its transcriptional and post-translational regulation, rarely involving post-transcriptional mechanism manipulated by certain indispensable microRNAs (miRNAs). Interestingly, we unveiled that miR-106b-5p, a widely expressed miRNA in various tissues, is up-regulated by Pb2+-induced stress. Moreover, we found a binding site for miR-106b-5p in the 3'-UTR of xiap mRNA using bioinformatics analysis, and provided the evidences that miR-106b-5p can interact and function with this regulatory region via luciferase reporter assay. Our results further showed that miR-106b-5p down-regulates XIAP protein level, and suppression of miR-106b-5p reverses the decrease in both XIAP level and cell viability in Pb2+-treated HT-22 and PC12 cells. In brief, we identified a novel function of miR-106b-5p in the post-transcriptional regulation of XIAP expression associated with Pb neurotoxicity. • Lead treatment induced miR-106b-5p expression in neuronal cells. • MiR-106b-5p affected the expression of xiap mRNA through interacting with 3'-UTR. • Induction of miR-106b-5p was responsible for lead-induced neuronal cell viability. [ABSTRACT FROM AUTHOR]

• MiR-106b-5p, as a cancer-related miRNAs, plays dual roles in cancers' development. • MiR-106b-5p, play its functions via post-transcriptionally regulating multiple target genes' expression. • MiR-106b-5p involves in the circRNA/lncRNA-miRNA-mRNA network in different cancer types. • MiR-106b-5p emerges as a promising prognostic biomarker for cancer. MicroRNAs (miRNAs), as a class of small, well-conserved, non-coding RNA molecules, hold the capacity to post-transcriptionally suppress the expression of over 50% protein-coding genes. Emerging and accumulating evidence suggests that miRNAs function as the master regulators of multiple pathophysiological processes, and play important roles in diverse human diseases, especially in tumorigenesis and progression. MiR-106b-5p, a member of miR‐106b seed family, has been demonstrated to be aberrantly expressed in human solid malignancies, and to play paradoxically opposing functions as an oncomiR or a tumor suppressor in tumor development. In addition, it has been recently reported to be a promising biomarker for prognostic evaluation for cancer patients. In the present review, we provided an overview to summarize the present findings of miR-106b-5p in cancer research fields, thereby establishing comprehensive understanding of its diverse functions and clinical implications in human cancers. [ABSTRACT FROM AUTHOR]

Introduction: Ovarian cancer (OC) is the malignant tumor with the highest mortality among gynecological cancers. Chemotherapy resistance is a major obstacle to OC therapy. Circular RNAs (circRNAs) play crucial roles in cancer development and chemoresistance. However, the role and potential mechanism of has-circ-001567 (circ-VPS13C) in chemoresistance of OC remain unknown., Material and Methods: The levels of circ-VPS13C, miR-106b-5p and 14-3-3 zeta (YWHAZ) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell Counting Kit-8 (CCK-8) assay was used to assess cell viability and calculate the half inhibition concentration (IC 50 ) of cisplatin (DDP). The levels of autophagy-related markers were measured by western blot assay. Cell apoptosis and migration were evaluated by flow cytometry and transwell assay, respectively. The binding relationship between miR-106b-5p and circ-VPS13C or YWHAZ was confirmed by dual-luciferase reporter assay. Xenograft assay was performed to explore the role of circ-VPS13C in vivo ., Results: Circ-VPS13C and YWHAZ were up-regulated, while miR-106b-5p was down-regulated in DDP-resistant OC tissues and cells. Knockdown of circ-VPS13C enhanced DDP sensitivity by repressing autophagy in DDP-resistant cells. Circ-VPS13C increased DDP resistance via sponging miR-106b-5p. Moreover, miR-106b-5p directly targeted YWHAZ. Up-regulation of YWHAZ alleviated the decrease in DDP resistance caused by circ-VPS13C depletion. In addition, circ-VPS13C silencing decreased DDP resistance in vivo ., Conclusions: Circ-VPS13C knockdown enhanced DDP sensitivity of OC through modulation of autophagy via the miR-106b-5p/YWHAZ axis, providing a new biomarker for improving the efficacy of OC chemotherapy., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia & Banach.)

Aim: Deepening our understanding of the molecular mechanism of abdominal aortic aneurysm (AAA) progression will help set up novel avenues for therapeutic target identification. Our aim here was to unveil the mechanism function of STAT3 in AAA progression., Methods: We investigated the functional role of STAT3 in AAA by evaluating vascular smooth muscle cell (VSMC) apoptosis and proliferation via terminal deoxynucleotidyl transferase dUTP nick end labeling, western blotting, 5-ethynyl-2´-deoxyuridine, and Cell Counting Kit-8 assays. The interplay of lncRNA-miRNA-mRNA was verified using the luciferase reporter assay and the RNA pull-down, RNA immunoprecipitation, and chromatin immunoprecipitation assays. Quantitative real-time polymerase chain reaction and western blot were utilized to quantitate the RNA and protein levels of the indicated molecules., Results: Inhibition of STAT3 facilitated VSMC proliferation and repressed VSMC apoptosis. Moreover, It was demonstrated that small nucleolar RNA host gene 16 (SNHG16) sponged miR-106b-5p to release STAT3 from the inhibitory effect of miR-106b-5p. SNHG16 led to the upregulation of STAT3, and STAT3 was an upstream factor in the activation of SNHG16 transcription. Moreover, rescue experiments indicated that SNHG16 depended on STAT3 to regulate VSMC apoptosis and proliferation. In vivo assays showed that SNHG16 knockdown retarded the formation of AAA and upregulated STAT3 in vivo., Conclusions: We identified that SNHG16/miR-106b-5p/STAT3 formed a complex circuitry for the deterioration of AAA via regulating VSMCs, suggesting a possible target for the pathogenesis of AAA.

Matrine is a main active constituent of Chinese herb Sophora flavescens Ait (Kushen), which has shown various pharmacological effects, and has been reported to exhibit protective effects in heart failure. In the present study, the underlying mechanism of matrine was explored in H2O2-induced H9c2 cell line. It was confirmed that matrine could alleviate H2O2-induced injury in H9c2 cells. And the down-regulation of long non-coding RNA HOTAIR induced by H2O2 could be reversed by treating with matrine. Moreover, overexpression of HOTAIR promoted cell viability and superoxide dismutase (SOD) level, but inhibited cell apoptosis and lactate dehydrogenase (LDH) level. We found that miR-106b-5p was a target of HOTAIR and negatively regulated by HOTAIR. Moreover, up-regulation of miR-106b-5p restored the effects of HOTAIR overexpression on cell viability, apoptosis, and the levels of LDH and SOD. In addition, matrine protected H9c2 cells from H2O2-induced injury through HOTAIR/miR-106b-5p axis. Furthermore, we discovered that matrine exerted protective effects on H2O2-induced H9c2 cells through activating STAT3 and AKT pathway. In brief, matrine modulated H2O2-induced myocardial oxidative stress repair through HOTAIR/miR-106b-5p axis via AKT and STAT3 signaling pathway. Our study may provide a therapeutic target for the therapy of oxidative stress heart diseases., (© 2020 The Author(s).)

Krüppel-like factor 10 (KLF10) has been identified as an important regulator in carcinogenesis and cancer progression. However, the role of KLF10 in multiply myeloma (MM) development and progression remains unknown. In present study, we found that KLF10 mRNA and protein were down-regulated in MM tissues and cell lines. Notably, KLF10 inhibited cell proliferation, cell cycle progression and promoted apoptosis in vitro and in vivo . Furthermore, we confirmed that KLF10 inhibited β-catenin nuclear translocation and inhibited PTTG1 transcription. PTTG1 knockdown could mimic the biological effects of KLF10. Moreover, we demonstrated that KLF10 expression was regulated by miR-106b-5p. In MM tissues, miR-106b-5p has an inverse correlation with KLF10 expression. Conclusively, our results demonstrated that KLF10 functions as a tumor suppressor in regulating tumor growth of MM under regulation of miR-106b-5p, supporting its potential therapeutic target for MM., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: Breast cancer has been the second most prevalent and fatal malignancy due to its frequent metastasis to other organs. We aim to study the effects of a key miRNA-mRNA signaling in breast cancer., Results: CNN1 was identified as the key gene in breast cancer by the bioinformatics analysis, and the downregulation of CNN1 in breast cancer tissues and cell lines was observed. Upregulating CNN1 inhibited cell survival, migration, invasion, and adhesion, but enhanced cell apoptosis. miR-106b-5p not only bound to CNN1 mRNA 3'UTR, but also promoted lung metastasis in vivo . Besides, the miR-106b-5p mimic enhanced breast cancer canceration by targeting CNN1 and activating Rho/ROCK1 signaling pathway., Conclusion: Overall, our results proved that miR-106b-5p promoted the metastasis of breast cancer by suppressing CNN1 and activating Rho/ROCK1 pathway., Methods: Bioinformatics analysis was performed to select the key gene in breast cancer. The overexpression and knockdown of Calponin 1 (CNN1) in breast cancer cell lines were performed to conduct cell viability, migrating, invasion, proliferation, adhesion, and apoptosis experiments. To identify the role of miR-106b-5p and Rho/ROCK1 in CNN1-induced breast cancer, a dual-luciferase assay, tumor lung metastasis assay, transcript half-life assay, and Rho/ROCK1 inhibition assay were performed.

The present study aims to determine the association of microRNA-106b-5p (miR-106b-5p) expression with the clinicopathological features and prognosis of renal cell carcinoma (RCC). The formalin-fixed paraffin-embedded(FFPE) Tumor tissues were collected from 284 RCC patients. The expression of miR-106b-5p was examined by Reverse Transcription Real-time Quantitative Polymerase Chain Reaction (RT-qPCR), followed by correlation analysis with clinicopathological features and prognosis. Patient survival analysis was determined by the Kaplan-Meier method using the log-rank test was used for patient survival analysis, and the univariate and multivariate analysis was determined by a Cox's regression model. Kaplan-Meier analysis indicated that patients with high miR-106b-5p expression showed a significantly shorter overall survival, compared with patients with low miR-106b-5p expression (p = 0.001). Univariate and multivariate analysis considered miR-106b-5p expression as an independent risk factor for predicting the prognosis of RCC patients. No significant evident showed that the expression level of miR-106b was related to gender, age, tumor size or tumor stage. Also, the results above were verified by analyzing the data of 506 cases from The Cancer Genome Atlas database (TCGA). The results pointed out that the high expression of miR-106b-5p serves as an independent factor for predicting the worse prognosis of RCC patients. [ABSTRACT FROM AUTHOR]

Purpose: To examine the role of miR-106b-5p in regulating the cancer stem-cell-like phenotype in clear cell renal cell carcinomas (ccRCC)., Experimental Design: Real-time PCR was performed to evaluate miR-106b-5p levels in ccRCC cell lines and patients specimens. A series of in vivo and in vitro assays were performed to confirm the effect of miR-106b-5p on ccRCC stemness phenotype., Results: ccRCC cells and tissues expressed more miR-106b-5p than normal controls. Gain- and loss-of-function studies demonstrated that overexpression of miR-106b-5p in ccRCC cells increased the spheres formation ability and the proportion of side population cells. Ectopic expression of miR-106b-5p in ccRCC cells increased tumour growth rates and the number of metastatic colonies in the lungs by using an orthotopic kidney cancer model and a tail vein injection model, respectively. Mechanistic studies revealed that, miR-106b-5p has an activating effect on Wnt/β-catenin signalling. miR-106p-5p overexpression simultaneously targets multiple negative regulators of the Wnt/β-catenin pathway, namely, LZTFL1, SFRP1 and DKK2. In addition, we also confirmed that miR-106b-5p and its targets expression correlates with the overall-survival of ccRCC patients from TCGA., Conclusions: These findings suggest that miR-106b-5p mediates the constitutive activation of Wnt/β-catenin signalling, likely serving as a potential therapeutic target for ccRCC.