MicroRNA-205-5p suppresses the invasiveness of oral squamous cell carcinoma by inhibiting TIMP‑2 expression

MicroRNA-205-5p 通过抑制 TIMP-2 表达抑制口腔鳞状细胞癌的侵袭性

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作者:Hiroki Nagai, Shogo Hasegawa, Fumihiko Uchida, Takehito Terabe, Naomi Ishibashi Kanno, Koroku Kato, Kenji Yamagata, Satoshi Sakai, Shuichi Kawashiri, Hiroshi Sato, Toru Yanagawa, Hiroki Bukawa

Abstract

MicroRNAs (miRNAs or miRs) play important roles in carcinogenesis. The miRNA, miR-205-5p, has been reported to suppress the growth of various types of tumor; however, its functional contribution to oral squamous cell carcinoma (OSCC) is not yet clear. Thus, this study was conducted to determine the miRNA expression signatures in OSCC and to investigate the functional role of miR‑205‑5p in OSCC cells. We measured miR‑205‑5p expression by RT-qPCR, and examined the function of miR‑205‑5p by transfecting a miR‑205‑5p mimic or inhibitor into OSCC cells and measuring cell proliferation, migration and invasiveness. Genes targeted by miR‑205‑5p were identified using the TargetScan database and verified by western blot analysis, luciferase reporter assay and ELISA. We found that miR‑205‑5p was significantly downregulated in OSCC cell lines and tissue specimens. Following transfection of miR‑205‑5p mimic or inhibitor into the cancer cell lines, miR‑205‑5p overexpression significantly suppressed cancer cell migration and invasion. We further demonstrated that miR‑205‑5p directly targeted and regulated the tissue inhibitor of metalloproteinases‑2 (TIMP‑2) gene. The silencing of TIMP‑2 suppressed cancer cell invasion and the activation of pro‑matrix metalloproteinase‑2 (pro‑MMP‑2). These results suggest that TIMP‑2 promotes tumor progression, and that miR‑205‑5p directly regulates TIMP‑2, thereby suppressing pro‑MMP‑2 activation and inhibiting OSCC cell invasiveness. Our data describing the pathways regulated by miR‑205‑5p provide new insight into the mechanisms responsible for OSCC development and metastasis.

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