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 ^[1] ; Youwen Zhong ^[1] ; Hua Zhang ^[1] ; Mu Li ^[1]
  1. [1] Xi’an Jiaotong University, Xi’an, Shaanxi, China
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 39, Nº. 3, 2024, págs. 345-355
• Idioma: inglés
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• Resumen

  • 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.