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miR-543 通过靶向 CYP3A5 在口腔鳞状细胞癌中发挥 novel oncogene 的作用。

miR‑543 acts as a novel oncogene in oral squamous cell carcinoma by targeting CYP3A5.

机构信息

Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510140, P.R. China.

出版信息

Oncol Rep. 2019 Sep;42(3):973-990. doi: 10.3892/or.2019.7230. Epub 2019 Jul 11.

Abstract

MicroRNAs (miRNAs/miRs) are small non‑coding RNAs that can act as oncogenes or tumor‑suppressor genes in human cancer. Previous studies have revealed that abnormal expression of miRNAs is closely associated with tumor cell cycle, differentiation, growth and apoptosis. miR‑543 is expressed abnormally in a wide variety of cancers and has been associated with cellular proliferation, apoptosis, and invasion; however, the effect of miR‑543 remains unknown in oral squamous cell carcinoma (OSCC). In the present study, the expression level of miR‑543 in OSCC cell lines and tissues was investigated by RT‑qPCR. A series of experiments was then performed to elucidate the functions of miR‑543 in OSCC, such as CCK‑8 assay, colony formation assay, flow cytometry, cell cycle distribution assay and cell apoptosis assay and Transwell assay. miR‑543 expression was significantly upregulated in tumors from patients with OSCC and in OSCC cell lines. Overexpression of miR‑543 promoted the proliferation, invasion and migration of OSCC cell lines, and inhibited cell apoptosis. In addition, the present study identified cytochrome P450 family 3 subfamily A member 5 (CYP3A5) as a direct target of miR‑543 using software analysis and dual‑luciferase reporter assays. In conclusion, the results of the present study suggest that miR‑543 acts as a tumor promoter and serves a vital role in OSCC proliferation and invasion. These results confirm that miR‑543 may serve as a potential novel target for the treatment of OSCC.

摘要

微小 RNA(miRNA/miRs)是一种小的非编码 RNA,可在人类癌症中作为癌基因或肿瘤抑制基因发挥作用。先前的研究表明,miRNA 的异常表达与肿瘤细胞周期、分化、生长和凋亡密切相关。miR-543 在多种癌症中表达异常,与细胞增殖、凋亡和侵袭有关;然而,miR-543 在口腔鳞状细胞癌(OSCC)中的作用尚不清楚。在本研究中,通过 RT-qPCR 检测了 OSCC 细胞系和组织中 miR-543 的表达水平。然后进行了一系列实验,以阐明 miR-543 在 OSCC 中的功能,如 CCK-8 测定、集落形成测定、流式细胞术、细胞周期分布测定、细胞凋亡测定和 Transwell 测定。miR-543 在 OSCC 患者的肿瘤和 OSCC 细胞系中表达显著上调。miR-543 的过表达促进了 OSCC 细胞系的增殖、侵袭和迁移,并抑制了细胞凋亡。此外,本研究通过软件分析和双荧光素酶报告基因实验鉴定细胞色素 P450 家族 3 亚家族 A 成员 5(CYP3A5)为 miR-543 的直接靶标。综上所述,本研究结果表明,miR-543 作为一种肿瘤促进因子,在 OSCC 的增殖和侵袭中发挥着重要作用。这些结果证实,miR-543 可能成为治疗 OSCC 的一种新的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbcc/6667884/ef1756423100/or-42-03-0973-g00.jpg

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