microRNA-92b-3p augments colon cancer development through inhibiting KLF3.

Colon cancer (CC) is a tumor of the large intestine. miR-92b-3p is often deregulated in the tumorigensis. Here, the role of miR-92b-3p in the development of CC was investigated. miR-92b-3p and Kruppel-like factor 3 (KLF3) expression was examined in CC tissues and cells. miR-92b-3p inhibitor or KLF3 overexpression vector was transfected into CC cells, respectively to observe its role in CC cell proliferation, invasion, migration, and apoptosis. The targeting relationship between miR-92b-3p and KLF3 was validated. Meanwhile, rescue experiments were performed by co-transfection of miR-92b-3p inhibitor and KLF3 siRNA, followed by determining CC cell proliferation, invasion, migration, and apoptosis. Higher miR-92b-3p and lower KLF3 expression levels were observed in CC tissues and cells. miR-92b-3p inhibition or KLF3 overexpression reduced proliferation, invasion, and migration whereas induced apoptosis of CC cells. KLF3 was validated to be the target gene of miR-92b-3p. Depletion of KLF3 could reverse the antitumor role of miR-92b-3p inhibition in CC cells. miR-92b-3p augments CC development through inhibiting KLF3, which may confers a novel way to develop future treatment target.

MicroRNA-92b acts as an oncogene by targeting PTEN/AKT in NSCLC.

MicroRNAs can act as tumour suppressors or oncogenes by regulating cellular differentiation, proliferation and apoptosis, and the dysregulation of miRNA is involved in the occurrence and development of NSCLC. Here, we provided evidence that miR-92b as an oncogene in NSCLC by targeting PTEN/AKT. We found that miR-92b was up-regulated in human NSCLC tissues and cell lines. MiR-92b knockdown suppressed the NSCLC cells proliferation and migration in both in vivo and in vitro models. Conversely, miR-92b overexpression induced an aggressive phenotype. Moreover, miR-92b-mediated regulation of NSCLC cell proliferation and migration depended on binding to PTEN mRNA, which then led to the degradation of PTEN and activation of the downstream AKT signalling pathway. Overall, this study revealed the oncogenic roles of miR-92b in NSCLC by targeting PTEN/AKT, and provided novel insights for future treatments of NSCLC patients. SIGNIFICANCE OF THE STUDY: MiR-92b was up-regulated in human NSCLC tissues and cell lines. Our study demonstrated that miR-92b as an oncogene in NSCLC by targeting PTEN/AKT in both in vivo and in vitro models and provided novel insights for future treatments of NSCLC patients.

MiR-92b-3p promotes neurite growth and functional recovery via the PTEN/AKT pathway in acute spinal cord injury.

Emerging evidence indicates that microRNAs play an important role in neural remodeling, including neurite growth, after acute spinal cord injury (ASCI). This study aims to identify the mechanism by which miR-92b-3p regulates neurite growth in vivo and in vitro. Adult Sprague-Dawley rats were selected to establish the ASCI model, and the expressions of miR-92b-3p and phosphate and tensin homolog deleted on chromosome ten (PTEN) were quantified at different time points. The interaction between miR-92b-3p and PTEN was further detected in the PC12 cell line and dual-luciferase reporter assay. Neurite growth proteins (GAP43 and NF-200) were assessed by western blotting after miR-92b-3p mimics treatment. The PTEN/AKT pathway-related proteins and their roles in miR-92b-3p regulation were also identified using western blotting and immunofluorescence in vitro through LY294002, an AKT inhibitor. The effect of miR-92b-3p was further determined in vivo according to the Basso-Beattie-Bresnahan (BBB) Scale and GAP43 and NF-200 expressions. miR-92b-3p was downregulated after ASCI, while PTEN showed a simultaneous opposing trend. Overexpression of miR-92b-3p downregulated PTEN expression and promoted phosphorylation of AKT, as well as the expression of GAP43 and NF-200 in PC12 cells. Furthermore, the dual-luciferase reporter assay revealed that miR-92b-3p exerted its effect by targeting PTEN's 3'-untranslated regions and that this effect could be counteracted by AKT phosphorylation blocker LY294002 through western blotting and immunofluorescence. Moreover, miR-92b-3p could also improve the BBB scale as well as GAP43 and NF-200 expression levels in vivo. Collectively, these results indicate that miR-92b-3p promotes neurite growth and functional recovery through the PTEN/AKT pathway in ASCI.

Downregulation of microRNA-92b-3p suppresses proliferation, migration, and invasion of gastric cancer SGC-7901 cells by targeting Homeobox D10.

To investigate the effect and mechanism of microRNA-92b-3p (miR-92b-3p) targeting Homeobox D10 (HOXD10) on proliferation, migration, and invasion of gastric cancer, we detected the expression of miR-92b-3p and HOXD10 in SGC-7901 cells. The effects of miR-92b-3p or HOXD10 on proliferation, migration, invasion, and matrix metalloproteinase (MMP)-2/9 expression in SGC-7901 cells were measured by the Cell Counting Kit-8 assay, Transwell assay, and Western blot, respectively. The results showed that miR-92b-3p expression was increased, and HOXD10 expression was decreased in SGC-7901 cells, compared with human normal gastric epithelial cells GES-1. Functional experiments demonstrated that cell proliferation, migration, invasion, and expression of MMP-2/9 in SGC-7901 cells were significantly inhibited by miR-92b-3p silencing and HOXD10 overexpression. Moreover, HOXD10 was a potential target gene of miR-92b-3p as evidenced by the TargetScan software and double luciferase reporter assay. In the rescue experiment, knockdown of HOXD10, accompanied by higher expression of MMP-2/9, could significantly eliminate the inhibitory effects of miR-92b-3p silencing on cell proliferation, migration, and invasion. In conclusion, miR-92b-3p is highly expressed in gastric cancer SGC-7901 cells, and interfering with its expression might inhibit SGC-7901 cell proliferation, migration, and invasion via downregulating MMP-2/9 expression and targeting HOXD10.

MicroRNA-92b targets tumor suppressor gene FBXW7 in glioblastoma.

Introduction: Glioblastoma (GBM) is a highly aggressive and lethal primary brain tumor. Despite limited treatment options, the overall survival of GBM patients has shown minimal improvement over the past two decades. Factors such as delayed cancer diagnosis, tumor heterogeneity, cancer stem cell survival, infiltrative nature of GBM cells, metabolic reprogramming, and development of therapy resistance contribute to treatment failure. To address these challenges, multitargeted therapies are urgently needed for improved GBM treatment outcomes. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Dysregulated miRNAs have been identified in GBM, playing roles in tumor initiation, progression, and maintenance. Among these miRNAs, miR-92b (miRNA-92b-3p) has been found to be overexpressed in various cancers, including GBM. However, the specific target genes of miR-92b and its therapeutic potential in GBM remain poorly explored. Methods: Samples encompassed T98G, U87, and A172 human GBM cell lines, GBM tumors from Puerto Rican patients, and murine tumors. In-situ hybridization (ISH) assessed miR-92b expression in patient tumors. Transient and stable transfections modified miR-92b levels in GBM cell lines. Real-time PCR gauged gene expressions. Caspase 3 and Trypan Blue assays evaluated apoptosis and viability. Bioinformatics tools (TargetScanHuman 8.0, miRDB, Diana tools, miRWalk) predicted targets. Luciferase assays and Western Blots validated miRNA-target interactions. A subcutaneous GBM Xenograft mouse model received intraperitoneal NC-OMIs or miR92b-OMIs encapsulated in liposomes, three-times per week for two weeks. Analysis utilized GraphPad Prism 8; statistical significance was assessed using 2-tailed, unpaired Student's t-test and two-way ANOVA as required. Results: This study investigated the expression of miR-92b in GBM tumors compared to normal brain tissue samples, revealing a significant upregulation. Inhibition of miR-92b using oligonucleotide microRNA inhibitors (OMIs) suppressed GBM cell growth, migration, and induced apoptosis, while ectopic expression of miR-92b yielded opposite effects. Systemic administration of liposomal-miR92b-OMIs in GBM xenograft mice resulted in reductions in tumor volume and weight. Subsequent experiments identified F-Box and WD Repeat Domain Containing 7 (FBXW7) as a direct target gene of miR-92b in GBM cells. Discussion: FBXW7 acts as a tumor suppressor gene in various cancer types, and analysis of patient data demonstrated that GBM patients with higher FBXW7 mRNA levels had significantly better overall survival compared to those with lower levels. Taken together, our findings suggest that the dysregulated expression of miR-92b in GBM contributes to tumor progression by targeting FBXW7. These results highlight the potential of miR-92b as a therapeutic target for GBM. Further exploration and development of miR-92b-targeted therapies may offer a novel approach to improve treatment outcomes in GBM patients.

Specificity protein 1/microRNA-92b forms a feedback loop promoting the migration and invasion of head and neck squamous cell carcinoma.

In this study we report a novel specificity protein 1 (SP1)/microRNA-92b (miR-92b) feedback loop regulating the migration and invasion of head and neck squamous cell carcinoma (HNSCC). Microarray and real-time Polymerase Chain Reaction (PCR) were used to detect gene expression in HNSCC tissues and cell lines. Transwell migration, invasion, wound healing and cell counting kit - 8 (CCK-8) cell assays were used to compare cell migration, invasion and proliferation abilities. Chromatin Immunoprecipitation (ChIP) assays were used to detect SP1 binding to the miR-92b promoter. Western blot was used to detect protein levels. An in vivo tumorigenesis experiment was used to evaluate the effect of SP1 knockdown on tumor growth and protein levels were evaluated by immunohistochemistry. We found that the miR-92b expression level was elevated in HNSCC primary focus tissue compared with adjacent normal tissue, and a higher level of miR-92b was related to a higher clinical stage and worse prognosis of HNSCC patients. MiR-92b and SP1 mutually promoted each expression and cooperatively facilitated the migration, invasion and proliferation of HNSCC cells. A decreased level of SP1/miR-92b resulted in a restraint of in vivo tumor growth. In conclusion, our results suggest that the SP1/miR-92b feedback loop generally promotes HNSCC invasion and metastasis, thus presenting a possible therapeutic target in the treatment of HNSCC patients.

Altered expression of microRNA-92b-3p predicts survival outcomes of patients with prostate cancer and functions as an oncogene in tumor progression.

The global incidence of prostate cancer (PCa) has been increasing in recent years. Meanwhile, some studies have indicated the association between malignancies, such as lung and gastric cancer and PCa, and microRNAs (miRNAs). The present study was designed to assess the prognostic value of miR-92b-3p in patients with PCa and further investigate the biological function of miR-92b-3p. Real-time quantitative polymerase chain reaction was used to estimate the expression of miR-92b-3p in PCa tissues and cell lines compared with normal tissues and cells. Kaplan-Meier method was used to analyze the overall survival rate of patients with PCa. A Cox regression analysis was used to verify the prognostic value of miR-92b-3p. The biological function of miR-92b-3p was investigated using cell experiments. The findings of the present study revealed the upregulated expression of miR-92b-3p in PCa tissues and cells compared with normal tissues and cells. The overexpression of miR-92b-3p was significantly associated with the distant metastasis status and Tumor-Node-Metastasis stage of patients with PCa and predicted poor prognosis of PCa. In addition, the cell experiment results indicated that miR-92b-3p overexpression in PCa cells promoted cell proliferation, migration and invasion. The present study revealed that the overexpression of miR-92b-3p predicted poor prognosis in patients with PCa. Decreased expression of miR-92b-3p can suppress PCa cell proliferation, migration and invasion, which indicated that miR-92b-3p may function as an oncogene and serve as a novel therapeutic target for PCa.

The expression of NLK is functionally associated with colorectal cancers (CRC).

The regulatory mechanism of NLK in the carcinomagenesis and progression of colorectal cancer (CRC) remains unclear. Here, we identified a single nucleotide polymorphism (SNP) site of NLK (rs2125846) as a new susceptibility locus for CRC risk located within an intron of the human NLK gene in a Chinese population. NLK downregulation led to a decrease in the ability of proliferation and migration of RKO cells in vitro. The proportion of RKO apoptotic cells increased by interfering with the endogenous expression of NLK. We speculate that LncRNA XIST may upregulate NLK expression by downregulating miR-92b-3p, thereby promote the development of CRC. These results provide important information for the identification of novel potential targets for the prevention or treatment of CRC.

WITHDRAWN: Anti-inflammatory role and mechanism of microRNA-92b-3p in the progression of hypoxic pulmonary hypertension.

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MicroRNA-92b-3p suppresses angiotensin II-induced cardiomyocyte hypertrophy via targeting HAND2.

AIMS: The pathological cardiac hypertrophy will develop into heart failure, which has no effective treatment currently. Previous studies have proved that microRNAs (miRNAs) participate in the development of cardiac hypertrophy and regulate the pathological progress. In this study, we want to investigate the role of microRNA-92b-3p (miR-92b-3p) in cardiomyocyte hypertrophy and the mechanisms involved. MATERIALS AND METHODS: Neonatal mouse ventricular cells (NMVCs) were isolated from the hearts of 1-3-d-old newborn C57BL6 mice. The isolated NMVCs were induced hypertrophic phenotype by Angiotensin-II (Ang-II) and the cell size was examined by FITC-phalloidin staining assay. The expression of miR-92b-3p was determined by quantitative real-time PCR (qRT-qPCR). MRNA and protein level of ß-MHC, ACTA1 and HAND2 in NMVCs transfected with miR-92b-3p mimic and inhibition were assessed by RT-qPCR assay and western blot assay, respectively. Dual luciferase assay was used to verify the interaction between miR-92b-3p and the 3'-untranslated region (UTR) of HAND2 gene. KEY FINDINGS: MiR-92b-3p and HAND2 were significantly increased in Ang-II-induced NMVCs. Overexpression of miR-92b-3p can ameliorate Ang-II-induced cardiomyocyte hypertrophy. MiR-92b-3p negatively regulated HAND2 expression at the transcriptional level. Both miR-92b-3p mimic and HAND2 siRNA could efficiently inhibit Ang-II-induced hypertrophy in mouse cardiomyocytes. SIGNIFICANCE: MiR-92b-3p inhibits Ang-II-induced cardiomyocyte hypertrophy via targeting HAND2.

Exosome-shuttled miR-92b-3p from ischemic preconditioned astrocytes protects neurons against oxygen and glucose deprivation.

Ischemic preconditioning (IPC) exerts protective effects against ischemic cerebral injury. In the present study, an in vitro model of cerebral ischemia (oxygen and glucose deprivation, OGD) was established to investigate the neuroprotective mechanism of IPC. We found that conditioned medium (C.M.) from astrocytes rather than neurons nor microglia cell line BV2 exerted neuroprotection. Moreover, exosomes derived from OGD preconditioned astrocytes can be taken up by neurons and attenuated OGD-induced neuron death and apoptosis. High-throughput microRNA (miRNA) sequencing revealed that miR-92b-3p levels in exosomes released from preconditioned astrocytes were increased. Overexpression of miR-92b-3p in neurons with miR-92b-3p mimic achieved the same protective effects as C.M. from astrocytes. Thus, we propose that the mechanism of IPC may associate with astrocytes, and that exosome-mediated miR-92b-3p shuttle from preconditioned astrocytes to neurons participate in these process.

The E3 ubiquitin ligase CHIP/miR-92b/PTEN regulatory network contributes to tumorigenesis of glioblastoma.

Glioblastoma (GBM) is the most frequent, aggressive and fatal tumor in the central nervous system, while PTEN signaling is frequently deregulated in human GBM. We previously reported the up-regulation of the carboxyl terminal of Hsp70-interacting protein (CHIP) in GBM, however, the causal link between its dysregulation and tumorigenesis has not been established. Using miRNA microarrays and quantitative RT-PCR (qRT-PCR), we found activation of CHIP leads to increased transcription of miR-92b. Further studies in T98G and LN229 cells showed overexpression of miR-92b elicited reduction of PTEN and efficiently rescued glioma development in CHIP knock-down cells. The core pathway, PI3K/Akt pathway, was then upregulated, which promoted GBM cell proliferation. Meanwhile, genetic ablation of miR-92b could restore PTEN expression and inhibit glioma growth. These data demonstrate that the CHIP/miR-92b/PTEN axis serves as a new mechanism underlying GBM tumorigenesis, providing potential new therapeutic targets.

MicroRNA-92b inhibits epithelial-mesenchymal transition-induced migration and invasion by targeting Smad3 in nasopharyngeal cancer.

Increasing studies reports that aberrant miRNAs contribute to nasopharyngeal carcinoma (NPC) development and progression. However, the role of miR-92b in NPC remains unclear. In present research, we found that a reduced miR-92b expression in NPC tissues and cell lines. The clinical data showed that the down-regulated miR-92b expression was obviously associated with adverse prognostic characteristic. Furthermore, we confirmed that miR-92b was a novel independent prognostic symbol for predicting 5-year survival of NPC patients. MiR-92b overexpression inhibited cell migration, invasion and EMT progress, while down-regulated miR-92b reversed the effect. Besides, miR-92b could modulate Smad3 by directly binding to its 3'-UTR. In clinical samples of NPC, miR-92b inversely correlated with Smad3. Alternation of Smad3 expression at least partially abrogated the migration, invasion and EMT progress of miR-92b on NPC cells. In summary, our results indicated that miR-92b functioned as a tumor suppressor gene in regulating the EMT and metastasis of NPC via targeting Smad3, and may represent a novel potential therapeutic target and prognostic marker for NPC.

Integrin α6 promotes esophageal cancer metastasis and is targeted by miR-92b.

Tumor invasion and metastasis is responsible for the poor prognosis of esophageal squamous cell carcinoma (ESCC); therefore, exploring the mechanisms by which malignant cells disseminate, spread and flourish in secondary sites, as well as translating the bench results to clinical practice are in urgent need. Previous reports showed that integrin α6 increases in ESCC specimens and its dysregulated spatial localization correlates positively with the unfavorable outcome of ESCC patients. Here, we clarify that integrin α6 promotes invasion and metastasis of ESCC cells In vitro and in vivo. Mechanistically, decreased integrin α6 attenuates motility of malignant cells partially through deactivating Akt pathway, which is essential for ESCC cells motility. Moreover, integrin α6 serves as a genuine target of miR-92b in suppressing ESCC motility. Our results for the first time describe that miR-92b/integrin α6/Akt axis controls the motility of ESCC, thereby providing a promising diagnosis or therapeutic option.

Targeting myocyte-specific enhancer factor 2D contributes to the suppression of cardiac hypertrophic growth by miR-92b-3p in mice.

The role of microRNA-92b-3p (miR-92b-3p) in cardiac hypertrophy was not well illustrated. The present study aimed to investigate the expression and potential target of miR-92b-3p in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. MiR-92b-3p was markedly decreased in the myocardium of Ang-II-infused mice and of patients with cardiac hypertrophy. However, miR-92b-3p expression was revealed increased in Ang-II-induced neonatal mouse cardiomyocytes. Cardiac hypertrophy was shown attenuated in Ang-II-infused mice received tail vein injection of miR-92b-3p mimic. Moreover, miR-92b-3p inhibited the expression of atrial natriuretic peptide (ANP), skeletal muscle α-actin (ACTA1) and ß-myosin heavy chain (MHC) in Ang-II-induced mouse cardiomyocytes in vitro. Myocyte-specific enhancer factor 2D (MEF2D), which was increased in Ang-II-induced mouse hypertrophic myocardium and cardiomyocytes, was identified as a target gene of miR-92b-3p. Functionally, miR-92b-3p mimic, consistent with MEF2D siRNA, inhibited cell size increase and protein expression of ANP, ACTA1 and ß-MHC in Ang-II-treated mouse cardiomyocytes. Taken together, we demonstrated that MEF2D is a novel target of miR-92b-3p, and attenuation of miR-92b-3p expression may contribute to the increase of MEF2D in cardiac hypertrophy.

MicroRNA-92b augments sorafenib resistance in hepatocellular carcinoma via targeting PTEN to activate PI3K/AKT/mTOR signaling

Sorafenib (SOR) resistance is still a significant challenge for the effective treatment of hepatocellular carcinoma (HCC). The mechanism of sorafenib resistance remains unclear. Several microRNAs (miRNAs) have been identified as playing a role in impairing the sensitivity of tumor cells to treatment. We examined the mechanism behind the role of miR-92b in mediating sorafenib resistance in HCC cells. We detected that miR-92b expression was significantly upregulated in SOR-resistant HepG2/SOR cells compared to parental HepG2/WT cells. After transfection with miR-92b inhibitor, the proliferation of HepG2/SOR cells was remarkably weakened and rates of apoptosis significantly increased. PTEN was considered to be a functional target of miR-92b according to a luciferase reporter assay. Knockdown of PTEN significantly impaired the ability of miR-92b inhibitor on increasing sorafenib sensitivity of HepG2/SOR cells. Furthermore, we confirmed by western blotting and immunofluorescence that miR-92b can mediate sorafenib resistance by activating the PI3K/AKT/mTOR pathway in HCC cells by directly targeting PTEN. These findings further validate the mechanism of miR-92b in SOR resistance in HCC treatment.

MicroRNA-92b represses invasion-metastasis cascade of esophageal squamous cell carcinoma.

Invasion and metastasis are major contributors to cancer-caused death in patients suffered from esophageal squamous cell carcinoma (ESCC). To explore the microRNAs involved in regulating invasion-metastasis cascade of ESCC, we established two pairs of sublines (30-U/D and 180-U/D) with distinct motility capacity from two ESCC cell lines (KYSE30 and KYSE180). Screening of the differentially expressed microRNAs identified that microRNA-92b-3p (miR-92b) could dramatically inhibit invasion and metastasis of ESCC cells in vitro and in vivo. Subsequent studies showed that miR-92b exerted its inhibitory function through suppressing the expression of integrin αV (ITGAV), which further reduced phosphrylated FAK and impaired Rac1 activation. Moreover, higher expression of miR-92b in ESCC tissues correlated inversely with lymph node metastasis and indicated better prognosis. Together, these results for the first time describe how miR-92b suppresses the motility of ESCC cells and provide a promise for diagnosis or therapy of ESCC invasion and metastasis.

Role and mechanism of microRNA-92b-3p in esophageal squamous cell carcinoma analyzed by weighted gene co-expression network analysis / 中华消化杂志

Objective To screen the critical genes related to the development of esophageal squamous cell carcinoma ( ESCC ) by weighted gene co-expression network analysis ( WGCNA ) and to verify by experiments.Methods Gene expression data of ESCC were downloaded from gene expression omnibus (GEO) database based on gene chip platform ( GPL) 570, GPL571, GPL96/97 or GPL14613 platform, respectively. Meanwhile, the obtained differentially expressed genes together with gene expression data of 81 ESCC patients from the cancer genome atlas ( TCGA ) and clinical data were analyzed by WGCNA to set up co-expression networks including mRNA and microRNA ( miRNA ) . The expression of miRNA in ESCC tissues and paracancerous tissues was examined by quantitative real-time polymerase chain reaction ( RT-PCR ) .And the expression of target protein Kruppel like factor 4 ( KLF4 ) and desmocollin 2 ( DSC2 ) were detected by immunohistochemistry .After ESCC cell line ECA-109 cells were transfected with miRNA-92b-3p mimic, cell cycle was tested by flow cytometry ,the cell invasion and migration ability was measured by Transwell chamber assay and scratch-wound assay.The expression of KLF4 and DSC2 was observed by confocal laser scanning microscopy and Western blotting .The target genes were verified by luciferase assay .T-test, rank sum test, chi-square test and Pearson correlation analysis were performed for statistical analysis .Results A total of 4023 differential expression gene ( DEG) and 328 differential expression miRNA ( DEM) were screened and 11 gene modules were set up by WGCNA .Among them, the brown modules were negatively associated with tumor grade and T stage (r=-0.340 and -0.268, P=0.002 and 0.016).Meanwhile, has-miR-92b and the potential target genes KLF4 and DSC2 were all in the brown module .Furthermore, the results of RT-PCR showed the expression of miRNA-92b-3p in ESCC tissues was higher than that in paracancerous tissues (3.052(1.652, 5.371) vs.0.985(0.558, 2.032)), and the difference was statistically significant (Z=-4.021,P<0.01). The results of immunohistochemistry demonstrated that the positive rates of KLF 4 and DSC2 in ESCC tissues were 43.3％(13/30) and 20.0％(6/30), respectively, which were lower than those of paracancerous tissues (70.0％(21/30) and 63.3％(19/30)), and the differences were statistically significant (χ2 =4.344 and 1.589, both P<0.05).After ECA-109 cells were transfected with miRNA-92b-3p mimics, the percentage of cells at G0/G1 phase decreased ((63.71 ±2.83)％vs.(54.62 ±4.00)％) and the percentage of cells at the S phase and G2/M phase increased ((31.81 ±2.88)％vs.(41.20％±2.87)％, and (3.87 ±1.75)％vs. (8.10 ±1.71)％, respectively), and the differences were statistically significant (t =3.215, 4.000 and 2.998;P=0.032, 0.016 and 0.040).The invasion and migration ability of the cells were significantly improved (79.67 ±27.54 vs.280.33 ±46.18, (69.72 ±3.91)％ vs.(84.90 ±5.25)％), and the differences were statistically significant (t=6.465 and 4.019, P=0.003 and 0.016).The results of Western blotting indicated that, compared with control mimic group , the expression of KLF4 and DSC2 was both dramatically downregulated after transfected with miRNA-92b-3p mimics transfected (1.00 ±0.23 vs.0.42 ±0.03, 1.00 ±0.20 vs.0.55 ± 0.21), and differences were statistically significant (t=4.470 and 5.493, P=0.042 and 0.032).The results of luciferase assay demonstrated that miRNA-92b-3p could directly bind KLF4 and DSC2. Conclusion WGCNA is an efficient systemic biological approach by which miRNA-92b-3p is identified as a new cancer-promoting gene .

The miR-92b functions as a potential oncogene by targeting on Smad3 in glioblastomas.

MicroRNAs(miR) play an important role in cell growth, differentiation, proliferation and apoptosis, which can function either as oncogenes or as tumor suppressors in their effect on tumor growth. Smad3 is often underexpressed in very diverse types of malignant tumors and has an important tumor suppressive function; however, the underlying mechanism in solid cancer including glioblastomas(GBM) is not fully explored. The aim of this study is to explore the role of miR-92b in regulation of smad3 in GBM. In our study, we found that miR-92b expression was significantly increased in GBM tissues compared with normal brain tissues by Q-RT-PCR and in situ hybridization (P<0.01). However, expression of smad3 in GBM samples was significantly reduced compared with normal brain tissues by western blot and immunohistochemistry (P<0.05). Using 3'UTR luciferase reporter gene assay, we found that miR-92b directly affected smad3 expression in GBM cells by targeting the 3'-untranslated region. Silencing of miR-92b was able to significantly inhibit the viability of GBM cells in three GBM cell lines through up-regulating the TGF-beta/smad3/p21 signaling pathway in vitro. Furthermore, the tumor growth and the weight of U87 cells in the miR-92b inhibitor group were significantly inhibited when compared with that of the control group in vivo. Our data demonstrated that miR-92b may be considered as a tumor oncogene to promote GBM cell proliferation, and thus may serve as a potentially useful target for development of miRNA-based therapies in the future.