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MiR?93?5p regulates the occurrence and development of esophageal carcinoma epithelial cells by targeting TGF?R2.

ABSTRACT: Emerging studies have indicated that the dysregulation of microRNAs (miRNAs or miRs) plays a vital role in the development and metastasis of tumors. However, the role of miR?93?5p in esophageal carcinoma (EC) has not been extensively reported. The present study thus focused on the role of miR?93?5p and its downstream target in the occurrence and development of EC. Firstly, miRNA expression profiles associated with EC were accessed from the TCGA_ESCA dataset and analyzed. Subsequently, the expression patterns of miR?93?5p and TGF?R2 were characterized in the human esophageal cell line, Het?1A, and the human EC cell lines, TE?1, Eca?109 and EC9706, by RT?qPCR and western blot analysis. WST?1 assay, flow cytometry, Transwell assay, wound healing assay and bioinformatics analysis were used to explore their functions in EC cells. Finally, a dual?luciferase reporter assay was employed to determine the targeted association between miR?93?5p and TGF?R2. The results revealed that the expression of miR?93?5p was markedly higher in EC cell lines compared with that in the normal cell line. The overexpression of miR?93?5p facilitated cell proliferation, migration and invasion, and inhibited cell apoptosis. Additionally, TGF?R2 was identified as a functional target of miR?93?5p in EC cells, as judged by a series of in vitro experiments. Furthermore, it was found that the simultaneous overexpression of miR?93?5p and TGF?R2 almost had no effect on the biological behaviors of EC cells. On the whole, the present study demonstrates that miR?93?5p promotes the proliferation, migration and invasion, and inhibits the apoptosis of EC cells by targeting TGF?R2.

SUBMITTER: Cai Y

PROVIDER: S-EPMC7834964 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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miR‑93‑5p regulates the occurrence and development of esophageal carcinoma epithelial cells by targeting TGFβR2.

Cai Yibin Y Ruan Weizhong W Ding Jianming J Wei Ning N Wang Jianchao J Zhang Hong H Ma Ning N Weng Guibin G Su Wei Kun WK Lin Yijin Y Zhu Kunshou K

International journal of molecular medicine 20210115 3

Emerging studies have indicated that the dysregulation of microRNAs (miRNAs or miRs) plays a vital role in the development and metastasis of tumors. However, the role of miR‑93‑5p in esophageal carcinoma (EC) has not been extensively reported. The present study thus focused on the role of miR‑93‑5p and its downstream target in the occurrence and development of EC. Firstly, miRNA expression profiles associated with EC were accessed from the TCGA_ESCA dataset and analyzed. Subsequently, the expres ...[more]

PMID: 33448310

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Project description:BackgroundLacrimal adenoid cystic carcinoma (LACC) is one of the most common malignancies that affects lacrimal gland. MicroRNAs are known to play a crucial role as oncogenes or tumor suppressors. Specifically, miR-93 has been reported to play a crucial role in colorectal, breast, pancreatic, lung cancer and hepatocellular carcinoma. However, the role of miR-93 in LACC and the potential molecular mechanisms involved remain unknown. Therefore, we took the challenge to determine the involvement of miR-93 in the LACC by targeting BRMS1L.MethodA total of 5 adenoid cystic carcinoma (ACC) of lacrimal gland patient tissues and their plasma were examined. Three normal lacrimal glands and three normal serums were collected as a control group. After surgical resection, the specimens were preserved in liquid nitrogen and stored at - 80 °C until RNA extraction. Afterwards, LACC cells with miR-93-5p overexpression were subjected to qRT-PCR and western blot for epithelial-mesenchymal transition (EMT) markers levels. Ability of LACC cell migration, invasion, proliferation and apoptosis was examined by wounded healing, transwell, CCK-8 and apoptosis assays. Afterwards, TargetScan was used to predict putative targets of miR-93-5p. Then, the examination was performed whether miR-93-5p targets BRMS1L by the use of luciferase reporter assays and western blotting. Finally, immunohistochemical staining was sone and all the images were taken using a microscope (Nikon, Tokyo).ResultsOur results showed that miR-93 was overexpressed in tissues and plasma of LACC patients compared to healthy controls. MiR-93 downregulated E-cadherin expression while increasing N-cadherin expression and significantly inhibited luciferase activity. Furthermore, western blotting results confirmed that miR-93-5p could inhibit BRMS1L expression. The BRMS1L staining in LACC tissues was weaker than in normal controls. In addition, miR-93-5p revealed a reverse correlation with the expression of BRMS1L. In addition, significant upregulation of E-cadherin and downregulation of N-cadherin were found when LACC cells were transfected with BRMS1L. Finally, miR-93-5p significantly enhanced TOP/FOP luciferase activity. Upregulation of BRMS1L reduced TOP/FOP luciferase activity while further overexpression of miR-93-5p could not rescue Wnt signaling activity.ConclusionsOur findings report that miR-93 promotes LACC cell migration, invasion, and proliferation via targeting downregulation of BRMS1L through regulation of Wnt signaling pathway.

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MiR?93?5p regulates the occurrence and development of esophageal carcinoma epithelial cells by targeting TGF?R2.

Publications

miR‑93‑5p regulates the occurrence and development of esophageal carcinoma epithelial cells by targeting TGFβR2.

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