MicroRNA-103a curtails the stemness of non-small cell lung cancer cells by binding to OTUB1 through the Hippo signaling pathway

Abstract

Background Although dysfunction of microRNA-103a (miR-103a) has been implicated in various cancers, its relevance in non-small cell lung cancer (NSCLC) is unsettled. This study was designed with an aim to examine the molecular mechanism underlying the regulatory role of miR-103a in NSCLC.Methods Kaplan-Meier analysis was carried out to study the correlation between overall survival of NSCLC patients and miR-103a expression. RT-qPCR and Western blot were applied to evaluate the expression of relevant genes in tissues and cells. Sphere formation, MTS, flow cytometry as well as Transwell assays were conducted for characterizing the stemness. Dual-luciferase reporter gene assays were applied to clarify the binding relationship between miR-103a and ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1).Results miR-103a expression was diminished in NSCLC tissues and cells, whereas OTUB1 expression was increased. Higher miR-103 expression indicated better prognosis for patients with NSCLC. After overexpression of miR-103a, the cell viability and stemness were diminished, while the cycle arrest and apoptosis rate were facilitated, and the expression of p-YAP decreased significantly. The opposite trends were observed after miR-103a silencing. miR-103a lowered the expression of OTUB1, while overexpression of OTUB1 blocked the inhibition effects of miR-103a on NSCLC.Conclusion miR-103a/OTUB1/Hippo axis plays a possible role in modulating the malignant behavior and stemness of cells which might function as a possible therapeutic option for the management of NSCLC.

Involvement of the OTUB1‐YAP1 axis in driving malignant behaviors of head and neck squamous cell carcinoma

“…It is noteworthy that the significance of both OTUB1 and YAP has been underscored in lung, gastric, and breast cancers. 20,36,37 The Hippo signaling pathway serves as a crucial cellular signaling pathway that governs a wide range of biological processes. 38 In an active state of the Hippo pathway, the LATS1/2 kinase phosphorylates and inhibits YAP, leading to its sequestration in the cytoplasm.…”