MicroRNA-154-5p suppresses cervical carcinoma growth and metastasis by silencing Cullin2 in vitro and in vivo

Author:

Li Yaqin12,Wei Yimiao1,Zhang Honglei3,Bai Ying1,Wang Xiuting4,Li Qi1,Liu Yatao1,Wang Shuling5,Wang Jiapu6,Wen Songquan1,Li Jiarong5,Zhao Weihong1

Affiliation:

1. Department of Obstetrics and Gynecology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China

2. Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, China

3. Department of Pathology and Pathophysiology,Basic Medical College, Shanxi Medical University, Taiyuan, Shanxi Province, China

4. Department of Biochemistry and Molecular Biology,Basic Medical College, Shanxi Medical University, Taiyuan, Shanxi Province, China

5. Department of Epidemiology,School of Public Health, Shanxi Medical University, Taiyuan, Shanxi Province, China

6. Scientific Research Experiment Center, Central laboratory, The Affiliated Cardiovascular Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China

Abstract

Background MicroRNA-154-5p (miR-154-5p) plays a role in tumorigenesis in diverse human malignancies. Nevertheless, little is known about the mechanism by which miR-154-5p alters the growth and metastasis of cervical cancer. This research aimed to analyze the role of miR-154-5p in the pathology of cervical cancer in vitro and in vivo. Methods The level of miR-154-5p in human papillomavirus 16 positive cervical cancer cells was examined by real-time quantitative polymerase chain reaction. Bioinformatics predicted the downstream targets and potential functions of miR-154-5p. Furthermore, lentiviral technology was used to construct SiHa cell lines with stable up- and down-expression levels of miR-154-5p. Its differential expression effects on the progress and metastasis of cervical cancer were analyzed using cell culture and animal models. Results MiR-154-5p showed low expression in cervical cancer cells. Overexpression of miR-154-5p could markedly inhibit the proliferation, migration, and colony formation ability of SiHa cells, concomitantly leading to G1 arrest of the cell cycle, while silencing miR-154-5p triggered the opposite results. Meanwhile, overexpression of miR-154-5p restrained the growth and metastasis of cervical cancer by silencing CUL2 in vivo. Additionally, miR-154-5p reduced CUL2 level, and overexpression of CUL2 influenced the effect of miR-154-5p in cervical cancer. In conclusion, miR-154-5p restrained the growth and metastasis of cervical cancer by directly silencing CUL2.

Funder

National Natural Science Foundation of China

Outstanding Youth Fund Project of Shanxi Province

China Postdoctoral Science Foundation

Research Project Supported by Shanxi Scholarship Council of China

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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