RNA结合蛋白RNPC1通过稳定MST1/2 mRNA抑制子宫内膜癌细胞干性机制

Abstract

Background RNA binding protein RNPC1 has a tumor-suppressive role in various tumors, nevertheless, the role of RNPC1 in human endometrial cancer (EC) are never been reported. Material/Methods Western blot, quantitative polymerase chain reaction and sphere forming analysis were performed to evaluate the stem-like traits of cells and RNPC1-induced effects on EC cell stemness. RNA immunoprecipitation (RIP) was constructed to investigate the underlying mechanisms. Results The spheres formed by EC cells, named EC spheres, exhibited a remarkably higher stemness than the parental cells, which is characterized as the increase of sphere forming ability, ALDH1 activity, stemness marker expression and migration ability. Notably, RNPC1 expression was decreased in poorly differentiated EC cells than that in EC cells with moderately differentiated. Additionally, RNPC1 expression was significantly decreased in EC spheres and RNPC1 overexpression attenuated the stemness of EC spheres. Moreover, RNPC1 overexpression decreased the migration ability of EC spheres. Mechanistic studies showed that RNPC1 overexpression activated the Hippo pathway through directly binding to MST1/2. Inhibition of MST1/2 rescued RNPC1-mediated effects on EC sphere stemness. Conclusions Therefore, our results indicate a novel RNPC1/MST1/2 signaling responsible for EC cell stemness.