Upregulation of miR-205 induces CHN1 expression, which is associated with the aggressive behaviour of cervical cancer cells and correlated with lymph node metastasis

BMC Cancer

Yunfeng Li¹  Bin He²  Xiangbo Xu²  Haoqi Zhao²  Xihua Chen²  Jiedong Wang²  Shufang Wang²  Jianqing Hao³  Jianbing Liu³  Shuyan Liu⁴ 

[1] Basic Medical College, Hebei University of Chinese Medicine, 050017, Shijiazhuang, People’s Republic of China;Reproductive Physiology Laboratory, National Research Institute for Family Planning, 100081, Beijing, People’s Republic of China;School of Basic Medical Sciences, Shanxi Medical University, 030001, Taiyuan, People’s Republic of China;School of Pre-clinical Sciences, Guangxi Medical University, 530021, Nanning, People’s Republic of China;

关键词: Cervical cancer;    microRNA-205;    a1-chimaerin;    Migration;    Invasion;    Cancer gene;   

DOI  :  10.1186/s12885-020-07478-w

来源: Springer

【 摘 要 】

BackgroundCervical cancer is the leading cause of cancer-related death in women worldwide. However, the mechanisms mediating the development and progression of cervical cancer are unclear. In this study, we aimed to elucidate the roles of microRNAs and a1-chimaerin (CHN1) protein in cervical cancer progression.MethodsThe expression of miR-205 and CHN1 protein was investigated by in situ hybridisation and immunohistochemistry. We predicted the target genes of miR-205 using software prediction and dual luciferase assays. The expression of mRNAs and proteins was tested by qRT-PCR and western blotting respectively. The ability of cell growth, migration and invasion was evaluated by CCK-8 and transwell. Cell apoptosis was analysed by flow cytometry analysis.ResultsWe found that miR-205 and CHN1 were highly expressed in human cervical cancer tissue compared with paired normal cervical tissues. The CHN1 gene was shown to be targeted by miR-205 in HeLa cells. Interestingly, transfection with miR-205 mimic upregulated CHN1 mRNA and protein, while miR-205 inhibitor downregulated CHN1 in high-risk and human papilloma virus (HPV)-negative human cervical cancer cells in vitro,. These data suggested that miR-205 positively regulated the expression of CHN1. Furthermore, the miR-205 mimic promoted cell growth, apoptosis, migration, and invasion in high-risk and HPV-negative cervical cancer cells, while the miR-205 inhibitor blocked these biological processes. Knockdown of CHN1 obviously reduced the aggressive cellular behaviours induced by upregulation of miR-205, suggesting that miR-205 positively regulated CHN1 to mediate these cell behaviours during the development of cervical cancer. Furthermore, CHN1 was correlated with lymph node metastasis in clinical specimens.ConclusionsOur findings showed that miR-205 positively regulated CHN1 to mediate cell growth, apoptosis, migration, and invasion during cervical cancer development, particularly for high-risk HPV-type cervical cancer. These findings suggested that dysregulation of miR-205 and subsequent abnormalities in CHN1 expression promoted the oncogenic potential of human cervical cancer.

【 授权许可】

CC BY