LncRNA HCG18 upregulates TRAF4/TRAF5 to facilitate proliferation, migration and EMT of epithelial ovarian cancer by targeting miR-29a/b

Molecular Medicine

Qi-Hui Wu¹  Fan Zhang²  Bai-Hua Luo³  Qing-Ling Li³  Ke-Da Yang³ 

[1] Department of Gynecology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan Province, People’s Republic of China;Department of Gynecology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan Province, People’s Republic of China;Department of Physiology, School of Basic Medical Science, Central South University, 410008, Changsha, Hunan Province, People’s Republic of China;Department of Pathology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, 410008, Changsha, Hunan Province, People’s Republic of China;

关键词: lncRNA HCG18;    Epithelial ovarian cancer;    TRAF4;    TRAF5;   

DOI  :  10.1186/s10020-021-00415-y

来源: Springer

【 摘 要 】

BackgroundAlthough long noncoding RNA HLA complex group 18 (lncRNA HCG18) has been suggested to regulate cell growth in several tumours, the function of HCG18 in epithelial ovarian cancer (EOC) and its mechanism are still unclear.MethodsshRNAs were applied to reduce HCG18 and related genes. For overexpression of miRNA, a miRNA mimic was transfected into cells. Quantitative real-time PCR (qRT–PCR) was used to detect levels of HCG18, miR-29a/b, and mRNAs. MTT, colony formation, wound healing and Transwell assays were used to evaluate cell proliferation, migration and invasion, respectively. A luciferase reporter assay was utilized to evaluate NF-κB activity and the binding of miRNAs with HCG18 or TRAF4/5. BALB nude mice injected with cells stably expressing shHCG18 or shNC were used for in vivo modelling. Subcutaneous tumour growth was monitored in nude mice, and immunohistochemistry (IHC) was used to determine expression of the proliferation marker Ki67.ResultsAbnormal expression of HCG18 and miR-29a/b was observed in EOC tissues. Knockdown of HCG18 using shRNA inhibited proliferation, migration, EMT and the proinflammatory pathway in EOC cells. miR-29a/b mimics and TRAF4/5 knockdown exhibited effects similar to HCG18 knockdown. Further experiments suggested that HCG18 directly targets miR-29a/b and upregulates TRAF4/5 expression, which are inhibited by targeting miR-29a/b. Moreover, overexpression of TRAF4/5 antagonized the inhibitory effect of HCG18 knockdown, suggesting that they are involved in HCG18-mediated oncogenic effects. Silencing HCG18 reduced tumour size and levels of Ki67 and TRAF4/5 while increasing miR-29a/b levels in vivo.ConclusionsTaken together, our data revealed an oncogenic signalling pathway mediated by HCG18 in ovarian cell lines, which functions as a ceRNA of miR-29a/b and thus derepresses expression levels of TRAF4/5, facilitating NF-κB pathway-mediated promotion of EOC cell proliferation and migration.

【 授权许可】

CC BY