miR-302b is a potential molecular marker of esophageal squamous cell carcinoma and functions as a tumor suppressor by targeting ErbB4

Zhang, Mingxin; Yang, Qi; Zhang, Lingmin; Zhou, Suna; Ye, Wenguang; Yao, Qinglin; Li, Zongfang; Huang, Cheng; Qinsheng, Wen; Wang, Jingjie

doi:10.1186/1756-9966-33-10

Cited by 50 publications

(49 citation statements)

References 30 publications

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“…(Fig. S4) The reason for these results is that miR-302b not only inhibited the expression of GCNT3, but also modulated the expression of its target genes, such as ERBB4, IRF2, CXCR4 [34], AKT2/NF-kB/MMP-2 pathway [35], CDK2 [36], ErbB4 et al [37], and AKT2 [38]. As we know, one single miRNA can regulate a broad range of cellular processes including cell growth, proliferation and apoptosis, by post-translational modulation of the target genes [13].…”

Section: Discussionmentioning

confidence: 91%

Downregulation of N-Acetylglucosaminyltransferase GCNT3 by miR-302b-3p Decreases Non-Small Cell Lung Cancer (NSCLC) Cell Proliferation, Migration and Invasion

Ran

Guo

et al. 2018

Cell Physiol Biochem

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Background/Aims: GCNT3 is a member of N-acetylglucosaminyltransferase family involved with mucin biosynthesis. GCNT3 aberrant expression is known to promote the progression of several human cancers. However, its role in tumorigenesis and the progression of non-small cell lung cancer (NSCLC) has not been well-characterized. Our study investigated the functional mechanisms of GCNT3 regulated by microRNAs (miRNAs) in NSCLC. Methods: The differential expression of mRNAs in NSCLC tissues and matched adjacent non-cancerous lung tissues from patients in Xuanwei, Yunnan province, China, was screened via mRNA microarray. The expression of GCNT3 and its correlation with NSCLC progression was measured in 92 paired tumor tissues and adjacent normal tissues. The functions of GCNT3 in NSCLC cells and its underlying mechanisms were measured using siRNA and GCNT3-expression vectors. The miRNA immunoprecipitation (miRIP) method was used to identify the miRNAs targeting GCNT3. The protein were measured using western blot assay, and the mRNAs were measured by quantitative real-time PCR (qRT-PCR) assay. Cell proliferation was measured using Cell Counting Kit-8 (CCK-8) and a colony forming assays; cell migration and invasion assays were performed using 24-well Transwell chambers with 8-μm pores filter, and analyses of the cell cycle and apoptosis were performed via flow cytometric analysis. The dual luciferase reporter assay was performed to confirm whether GCNT3 gene was a direct target of miR-302b-3p. Results: GCNT3 was found to be highly expressed in both NSCLC tissues and cell lines, and higher expression correlated significantly with advanced tumor-node-metastasis (TNM) stage, positive lymph node metastasis, and poor overall survival. Knockdown of GCNT3 inhibited the proliferation, migration and invasion ability of NSCLC cells, while overexpression facilitated these activities. Further mechanistic experiments using miRIP and dual luciferase reporter assays revealed that GCNT3 was a direct target of miR-302b-3p. Low expression of miR-302b-3p was found in NSCLC cells and negatively correlated with GCNT3 levels, while miR-302b-3p overexpression inhibited the proliferation, migration and invasion of NSCLC cells. Co-transfection with miR-302b-3p and the expression vector of GCNT3 abrogated the effects of mir-302b-3p, confirming that miR-302b-3p inhibited NSCLC progression by targeting GCNT3. Western blotting revealed that E-cadherin, N-cadherin, vimentin, p-Erk and cyclin D1 were downstream molecules of miR-302b-3p/GCNT3 pathway. Conclusion: miR-302b-3p/GCNT3 axis regulated cell proliferation, migration, and invasion by activating the Erk signaling pathway and epithelial-mesenchymal transition (EMT), which was identified as a potential therapeutic target for NSCLC.

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Section: Discussionmentioning

confidence: 91%

Downregulation of N-Acetylglucosaminyltransferase GCNT3 by miR-302b-3p Decreases Non-Small Cell Lung Cancer (NSCLC) Cell Proliferation, Migration and Invasion

Ran

Guo

et al. 2018

Cell Physiol Biochem

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“…By contrast, miR-197 was downregulated in esophageal cancer with a poor prognosis, and may play a tumor-suppressor role (13). Additionally, miR-302b inhibited cell proliferation by inducing apoptosis and suppressing the invasion in esophageal squamous cell carcinoma (14). miRNA profiling has shown that microRNA-374a (miR-374a) is overexpressed in many types of cancer, such as head and neck squamous cell carcinoma, follicular lymphoma, osteosarcoma and bladder urothelial carcinoma (15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 94%

MicroRNA-374a promotes esophageal cancer cell proliferation via Axin2 suppression

et al. 2015

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Abstract. is involved in the progress of various types of cancer, and may indicate a poor prognosis. However, its role in esophageal cancer remains to be determined. In the present study, the role of miR-374a in esophageal cancers and cancer cell growth was examined using miR-374a overexpression and underexpression models. The results showed that miR-374a was markedly increased in esophageal cancer cell lines and tumor samples from patients with esophageal cancer. In esophageal cancer Eca109 cells, the ectopic overexpression of miR-374a promoted cell growth. Additionally, cell growth was reduced by miR-374a inhibition. The mechanisms underlying the promotive role were examined and it was found that miR-374a significantly decreased the expression and transcription activity of axis inhibition protein 2 (Axin2). Axin2, a tumor suppressor, exhibited a marked inhibitory effect on Eca109 cell growth. The results identified a new role of miR-374a in esophageal cancer involving Axin2 suppression.

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“…MiR-302b is a member of the miR-302 cluster, which consists of four homologous miRNAs that are transcribed as a noncoding RNA cluster and are specifically expressed in human and mouse embryonic stem cells [17]. MiR-302b acts as a tumor suppressor in esophageal squamous cell carcinoma and it is downregulated in hepatocellular carcinoma, where it inhibits cell proliferation by targeting EGFR [18,19]. Although genome-wide miRNA expression profiling studies showed that miR-302b is downregulated in ovarian carcinoma [14,20], the exact role of miR-302b in EOC remains unknown.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-302b Suppresses Human Epithelial Ovarian Cancer Cell Growth by Targeting RUNX1

Yin

Yang

et al. 2014

Cell Physiol Biochem

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Background: The microRNA (miR)-302 family functions as a tumor suppressor in human cancer. However, its role in epithelial ovarian carcinoma (EOC) remains unknown. Here, we investigated the role of miR-302b and its target gene RUNX1 in EOC. Methods: The expression levels of miR-302b and RUNX1 were assessed by quantitative real-time PCR and western blotting. The effects of ectopic expression of miR-302b were evaluated by the MTT assay, colony forming assay and flow cytometry. RUNX1 was identified as a target of miR-302b and their interaction was confirmed by luciferase activity assays, RUNX1 silencing and overexpression of a RUNX1 mutant construct lacking the 3′UTR. The effect of miR-302b on the suppression of tumor growth was investigated in vivo in a xenograft mouse model. Results: MiR-302b levels were markedly decreased in EOC specimens. Ectopic expression of miR-302b in EOC cells inhibited cell proliferation and colony formation, induced G0/G1 arrest, and promoted apoptosis. RUNX1 was identified as a direct target of miR-302b, and knockdown of RUNX1 inhibited cell growth in a manner similar to miR-302b overexpression, whereas introduction of a 3′UTR mutant of RUNX1 reversed the suppressive effect of miR-302b. Furthermore, miR-302b overexpression led to the inactivation of the STAT3 signaling pathway in EOC cells and inhibited tumor growth in a xenograft mouse model. Conclusions: MiR-302b functions as a tumor suppressor in EOC by targeting RUNX1 and modulating the activity of the STAT3 signaling pathway.

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miR-302b is a potential molecular marker of esophageal squamous cell carcinoma and functions as a tumor suppressor by targeting ErbB4

Cited by 50 publications

References 30 publications

Downregulation of N-Acetylglucosaminyltransferase GCNT3 by miR-302b-3p Decreases Non-Small Cell Lung Cancer (NSCLC) Cell Proliferation, Migration and Invasion

Downregulation of N-Acetylglucosaminyltransferase GCNT3 by miR-302b-3p Decreases Non-Small Cell Lung Cancer (NSCLC) Cell Proliferation, Migration and Invasion

MicroRNA-374a promotes esophageal cancer cell proliferation via Axin2 suppression

MicroRNA-302b Suppresses Human Epithelial Ovarian Cancer Cell Growth by Targeting RUNX1

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