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微小RNA-34a直接靶向高迁移率族蛋白盒1,并抑制皮肤鳞状细胞癌中的癌细胞增殖、迁移和侵袭。

MicroRNA-34a directly targets high-mobility group box 1 and inhibits the cancer cell proliferation, migration and invasion in cutaneous squamous cell carcinoma.

作者信息

Li Shanshan, Luo Chengqun, Zhou Jun, Zhang Yong

机构信息

Department of Plastic and Reconstructive Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100144, P.R. China.

Department of Burns, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.

出版信息

Exp Ther Med. 2017 Dec;14(6):5611-5618. doi: 10.3892/etm.2017.5245. Epub 2017 Oct 2.

Abstract

Cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer with increasing incidence. In recent years, several microRNAs (miRs) have been demonstrated to serve an oncogenic or tumor suppressive role in CSCC. However, the exact role of miR-34a in CSCC and the underlying regulatory mechanism remain unclear. The present study aimed to investigate the regulatory mechanism of miR-34a in the malignant phenotypes of CSCC cells using MTT assay, wound healing assay and transwell assay. It was observed that miR-34a was significantly downregulated in CSCC tissues and cell lines, and low miR-34a expression was associated with the aggressive progression of CSCC. Restoration of miR-34a significantly suppressed the proliferation, migration and invasion of CSCC SCL-1 cells. High-mobility group box 1 (HMGB1) was then identified as a target gene of miR-34a in SCL-1 cells using bioinformatics prediction. The expression of HMGB1 was significantly upregulated in the CSCC tissues and cell lines. Furthermore, the protein expression of HMGB1 was negatively regulated by miR-34a in SCL-1 cells, while overexpression of HMGB1 impaired the inhibitory effects of miR-34a on SCL-1 cells. These findings suggest that miR-34a represses the malignant phenotypes of CSCC cells, at least partly, via the inhibition of HMGB1. Therefore, miR-34a may be used as a promising therapeutic candidate for CSCC.

摘要

皮肤鳞状细胞癌(CSCC)是第二常见的皮肤癌类型,其发病率呈上升趋势。近年来,几种微小RNA(miR)已被证明在CSCC中发挥致癌或抑癌作用。然而,miR-34a在CSCC中的确切作用及潜在调控机制仍不清楚。本研究旨在通过MTT法、伤口愈合试验和Transwell试验研究miR-34a在CSCC细胞恶性表型中的调控机制。结果发现,miR-34a在CSCC组织和细胞系中显著下调,且miR-34a低表达与CSCC的侵袭性进展相关。miR-34a的恢复显著抑制了CSCC SCL-1细胞的增殖、迁移和侵袭。随后,通过生物信息学预测确定高迁移率族蛋白B1(HMGB1)为SCL-1细胞中miR-34a的靶基因。HMGB1在CSCC组织和细胞系中的表达显著上调。此外,miR-34a在SCL-1细胞中对HMGB1的蛋白表达具有负调控作用,而HMGB1的过表达削弱了miR-34a对SCL-1细胞的抑制作用。这些发现表明,miR-34a至少部分通过抑制HMGB1来抑制CSCC细胞的恶性表型。因此,miR-34a可能是CSCC一种有前景的治疗候选物。

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