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

• Published in: BMC cancer Vol. 20; no. 1; pp. 1029 - 13
• Main Authors: Liu, Jianbing, Li, Yunfeng, Chen, Xihua, Xu, Xiangbo, Zhao, Haoqi, Wang, Shufang, Hao, Jianqing, He, Bin, Liu, Shuyan, Wang, Jiedong
• Format: Journal Article
• Language: English
• Published: London BioMed Central 27.10.2020; BioMed Central Ltd; BMC
• Subjects: a1-chimaerin; Apoptosis; Binding proteins; Biomedical and Life Sciences; Biomedicine; Cancer gene; Cancer Research; Care and treatment; Cell and molecular biology; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Cervical cancer; Chimerin 1 - genetics; Chimerin 1 - metabolism; Cholecystokinin; Complications and side effects; Female; Flow cytometry; Gene expression; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Genetic aspects; Health aspects; Health Promotion and Disease Prevention; HeLa Cells; Human papillomavirus; Humans; Hybridization; Immunohistochemistry; Invasion; Laboratories; Lymph nodes; Lymphatic metastasis; Lymphatic Metastasis - genetics; Medical research; Medicine/Public Health; Metastases; Metastasis; MicroRNA; microRNA-205; MicroRNAs; MicroRNAs - genetics; Migration; miRNA; mRNA; Mutagenesis; Oncology; Proteins; Research Article; Surgical Oncology; Thermal cycling; Transfection; Up-Regulation; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Western blotting; China; Beijing China; United States > US; Japan; a1-chimaerin; Migration; Cervical cancer; microRNA-205; Invasion; Cancer gene
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-020-07478-w

Background Cervical 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. Methods The 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. Results We 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. Conclusions Our 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.