Resumen de MiR-5590-3p inhibits the proliferation and invasion of ovarian cancer cells through mediating the Wnt/β-catenin signaling pathway by targeting TNIK
Xiaoling Wu, Youwen Zhong, Hua Zhang, Mu Li
MicroRNAs (miRNAs) are crucial regulatory molecules involved in diverse biological processes and human diseases, including ovarian cancer (OC). miR5590-3p has been involved in multiple malignant solid tumors, but its exact role in the progression of OC is largely unknown. This study mainly focuses on how miR-5590-3p works in OC and illuminating the underlying mechanism. We found that miR-5590-3p was significantly downregulated in human OC cell lines and patient tissues. Cell counting 8 (CCK-8) and Transwell assays proved that overexpression or inhibition of miR5590-3p suppressed or promoted cell proliferation and cell invasion. Subsequently, TNIK was identified as a target of miR-5590-3p. Silence of TNIK by small interfering RNA (siRNA) reversed the increasing effect of miR-5590-3p inhibition on cell proliferation and invasion in OC cell lines. Furthermore, our results showed that the Wnt/β-catenin pathway was inhibited by its specific inhibitor XAV-939, but miR-5590-3p inhibitor and adenoviral TNIK overexpression vector (Ad-TNIK) reactivated the activation of Wnt/β-catenin signaling and increased cell malignancy. Lastly, tumorigenicity assay demonstrated that inhibition of miR-5590-3p increased tumor volume and weight in vivo. In conclusion, miR-5590-3p may function as a cancer suppressor gene in OC progression through the Wnt/β-catenin signaling by transcriptionally suppressing TNIK expression, which provides a potential therapeutic approach for ovarian cancer treatment.
