miR-30a attenuates drug sensitivity to 5-FU by modulating cell proliferation possibly by downregulating cyclin E2 in oral squamous cell carcinoma

Biochemistry and Biophysics Reports

Sho Kawaguchi¹  Hikaru Nakashima²  Akiyuki Hirosue²  Nozomu Takahashi²  Yuichiro Matsuoka²  Yuka Nagao²  Hideki Nakayama²  Keisuke Yamana²  Masashi Nagata²  Masatoshi Hirayama³  Shunsuke Gohara³  Mayumi Hirayama³  Ryoji Yoshida³  Kenta Kawahara³  Hidetaka Arita³  Junki Sakata³  Takuya Tanaka³ 

[1] Department of Dentistry and Oral Surgery, Amakusa Central General Hospital, Amakusa 863-0033, Japan;Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan;;Department of Oral &

关键词: Five-fluorouracil;    Drug resistance;    microRNA;    miR-30a;    Cyclin E2;    Oral squamous cell carcinoma;   

DOI  :  

来源: DOAJ

【 摘 要 】

We aimed to determine the functional role of the miRNA, which affects drug sensitivity to 5-FU in oral squamous cell carcinoma (OSCC), using two types of 5-FU-resistant and parental OSCC cell lines. MiRNA microarray data showed that miR-30a was significantly upregulated in two resistant cell lines. Therefore, we investigated the effects and molecular mechanism of miR-30a on 5-FU sensitivity. Stable overexpression of miR-30a in parental OSCC cells decreased cell proliferation and attenuated drug sensitivity to 5-FU. Cell cycle analysis indicated that miR-30a overexpression increased the proportion of G1 phase cells and decreased the proportion of S phase cells. MiR-30a knockdown using siRNA reversed the effects of miR-30a overexpression. DNA microarray analysis using miR-30a-overexpressing cell lines and a TargetScan database search showed that cyclin E2 (CCNE2) is a target of miR-30a. A luciferase reporter assay confirmed that a miR-30a mimic interacted with the specific binding site in the 3' UTR of CCNE2. CCNE2 knockdown with siRNA in OSCC cells yielded decreased drug sensitivity to 5-FU, similar to miR-30a overexpressing cells. These findings suggest that miR-30a in OSCC may be a novel biomarker of 5-FU-resistant tumors, as well as a therapeutic target for combating resistance.

【 授权许可】

Unknown