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Overexpression of microRNA-203 Suppresses Proliferation, Invasion, and Migration while Accelerating Apoptosis of CSCC Cell Line SCL-1.

ABSTRACT: Cutaneous squamous cell carcinoma (CSCC) is a malignant proliferation of cutaneous epithelium that has been observed to have an alarming rise in incidence. Numerous studies have demonstrated microRNAs (miRNAs or miRs) as important biomarkers in the diagnosis, prognosis, and treatment of CSCC. This study aims to investigate the effects of miR-203 on the behaviors of CSCC cells and possible mechanisms associated with protein regulator of cytokinesis-1 (PRC1) and Wnt/?-catenin signaling pathway. PRC1 was suggested as a target of miR-203 in squamous cell carcinoma cell line 1 (SCL-1) cells by dual-luciferase reporter gene assay. Based on the immunohistochemical staining and qRT-PCR, PRC1 was abundantly expressed while miR-203 was poorly expressed in CSCC tissues. miR-203 mimic or inhibitor was transfected into SCL-1 cells to upregulate or downregulate its expression. Upregulation of miR-203 downregulated PRC1 expression to block the Wnt/?-catenin signaling pathway. By conducting 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), scratch test, and Transwell and flow cytometric analyses, miR-203 was witnessed to restrain SCL-1 cell proliferation, migration, and invasion while accelerating their apoptosis. The rescue experiments addressed that inhibition of the Wnt/?-catenin signaling pathway conferred the anti-tumor effect of miR-203. These results establish a tumor-suppressive role for miR-203 in CSCC cell line SCL-1. Hence, miR-203 has promising potential as a therapeutic target for CSCC.

SUBMITTER: Ting W

PROVIDER: S-EPMC7358222 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Overexpression of microRNA-203 Suppresses Proliferation, Invasion, and Migration while Accelerating Apoptosis of CSCC Cell Line SCL-1.

Ting Wenyun W Feng Cheng C Zhang Mingzi M Long Fei F Bai Ming M

Molecular therapy. Nucleic acids 20200501

Cutaneous squamous cell carcinoma (CSCC) is a malignant proliferation of cutaneous epithelium that has been observed to have an alarming rise in incidence. Numerous studies have demonstrated microRNAs (miRNAs or miRs) as important biomarkers in the diagnosis, prognosis, and treatment of CSCC. This study aims to investigate the effects of miR-203 on the behaviors of CSCC cells and possible mechanisms associated with protein regulator of cytokinesis-1 (PRC1) and Wnt/β-catenin signaling pathway. PR ...[more]

PMID: 32668390

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Project description:BackgroundMicroRNAs (miRNAs) are crucial molecules that regulate gene expression and hence pathways that are key to prostate cancer progression. These non-coding RNAs are highly deregulated in prostate cancer thus facilitating progression of the disease. Among the many genes that have gained importance in this disease, Migration and invasion enhancer 1 (MIEN1), a novel gene located next to HER2/neu in the 17q12 amplicon of the human chromosome, has been shown to enhance prostate cancer cell migration and invasion, two key processes in cancer progression. MIEN1 is differentially expressed between normal and cancer cells and tissues. Understanding the regulation of MIEN1 by microRNA may enable development of better targeting strategies.MethodsThe miRNAs that could target MIEN1 were predicted by in silico algorithms and microarray analysis. The validation for miRNA expression was performed by qPCR and northern blotting in cells and by in situ hybridization in tissues. MIEN1 and levels of other molecules upon miRNA regulation was determined by Western blotting, qPCR, and immunofluorescence. The functional effects of miRNA on cells were determined by wound healing cell migration, Boyden chamber cell invasion, clonal and colony formation assays. For knockdown or overexpression of the miRNA or overexpression of MIEN1 3'UTR, cells were transfected with the oligomiRs and plasmids, respectively.ResultsA novel miRNA, hsa-miR-940 (miR-940), identified and validated to be highly expressed in immortalized normal cells compared to cancer cells, is a regulator of MIEN1. Analysis of human prostate tumors and their matched normal tissues confirmed that miR-940 is highly expressed in the normal tissues compared to its low to negligible expression in the tumors. While MIEN1 is a direct target of miR-940, miR-940 alters MIEN1 RNA, in a quantity as well as cell dependent context, along with altering its downstream effectors. The miR-940 inhibited migratory and invasive potential of cells, attenuated their anchorage-independent growth ability, and increased E-cadherin expression, implicating its role in mesenchymal-to-epithelial transition (MET).ConclusionsThese results, for the first time, implicate miR-940, a regulator of MIEN1, as a promising novel diagnostic and prognostic tool for prostate cancer.

Dataset Information

Overexpression of microRNA-203 Suppresses Proliferation, Invasion, and Migration while Accelerating Apoptosis of CSCC Cell Line SCL-1.

Publications

Overexpression of microRNA-203 Suppresses Proliferation, Invasion, and Migration while Accelerating Apoptosis of CSCC Cell Line SCL-1.

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