Screening and identification of miR-181a-5p in oral squamous cell carcinoma and functional verification in vivo and in vitro

BMC Cancer

Research

Zhaoyang Chen¹  Xiaotang Wang¹  Jiping Gao¹  Litao Qin¹  Ruijing Xuan¹  Guohua Song¹  Lanfei Xiao¹  Yiyan Yang²  Guoqiang Xu²  Junting Yang²  Rui Sun³  Xiaofen Wu⁴ 

[1]Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model, Shanxi Medical University, Road Xinjian 56, 030001, Taiyuan, China

[2]Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model, Shanxi Medical University, Road Xinjian 56, 030001, Taiyuan, China

[3]Shanxi Medical University School of Basic Medical Science, 030001, Taiyuan, China

[4]Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 030032, Taiyuan, China

[5]Shanxi Medical University School and Hospital of Stomatology, 030001, Taiyuan, China

关键词: miRNAs;    OSCC;    Chinese hamster animal model;    miR-181a-5p/BCL2 axis;   

DOI  :  10.1186/s12885-023-10600-3

 received in 2022-07-16, accepted in 2023-02-01,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundOral squamous cell carcinoma (OSCC) is a common malignant tumor associated with poor prognosis. MicroRNAs (miRNAs) play crucial regulatory roles in the cancer development. However, the role of miRNAs in OSCC development and progression is not well understood.MethodsWe sought to establish a dynamic Chinese hamster OSCC animal model, construct miRNA differential expression profiles of its occurrence and development, predict its targets, and perform functional analysis and validation in vitro.ResultsUsing expression and functional analyses, the key candidate miRNA (miR-181a-5p) was selected for further functional research, and the expression of miR-181a-5p in OSCC tissues and cell lines was detected. Subsequently, transfection technology and a nude mouse tumorigenic model were used to explore potential molecular mechanisms. miR-181a-5p was significantly downregulated in human OSCC specimens and cell lines, and decreased miR-181a-5p expression was observed in multiple stages of the Chinese hamster OSCC animal model. Moreover, upregulated miR-181a-5p significantly inhibited OSCC cell proliferation, colony formation, invasion, and migration; blocked the cell cycle; and promoted apoptosis. BCL2 was identified as a target of miR-181a-5p. BCL2 may interact with apoptosis- (BAX), invasion- and migration- (TIMP1, MMP2, and MMP9), and cell cycle-related genes (KI67, E2F1, CYCLIND1, and CDK6) to further regulate biological behavior. Tumor xenograft analysis indicated that tumor growth was significantly inhibited in the high miR-181a-5p expression group.ConclusionOur findings indicate that miR-181a-5p can be used as a potential biomarker and provide a novel animal model for mechanistic research on oral cancer.

【 授权许可】

CC BY   
© The Author(s) 2023

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