Background: Cervical cancer is a lethal gynecologic cancer in women. Long non-coding RNA colorectal neoplasia differentially expressed (LncRNA CRNDE) was recognized as a significant oncogene in multiple cancers. However, the functional role of CRNDE in cervical cancer remains poorly explored.
Methods: The expression of CRNDE, microRNA-4262 (miR-4262) and zinc-finger E-box binding homeobox 1 (ZEB1) in cervical cancer tumors and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Colony formation and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) were performed to detect cell viability. Flow cytometry and caspase-3 activity assay were conducted to evaluate cell apoptosis. The interaction between miR-4262 and CRNDE or ZEB1 was verified by dual-luciferase reporter system. Transwell assay was employed to evaluate cell migration and invasion. The relative protein expression was assessed by Western blot.
Results: CRNDE and ZEB1 were up-regulated, while miR-4262 was down-regulated in cervical cancer tissues and cells. We found that CRNDE sponged miR-4262 and ZEB1 was a target of miR-4262. In addition, miR-4262 inhibitor abolished CRNDE silencing-induced repression on cell proliferation, EMT, migration, invasion and promotion on cell apoptosis. Furthermore, ZEB1 rescued the effects of miR-4262 overexpression or CRNDE deletion on cervical cancer progression. Our data showed that CRNDE targeted miR-4262 to regulate ZEB1 expression in cervical cancer cells. Besides, CRNDE expedited cervical cancer progression through wnt/β-catenin pathway via sponging miR-4262 and altering ZEB1 expression.
Conclusion: Our findings demonstrated that CRNDE facilitated the progression of cervical cancer through activation of wnt/β-catenin pathway by regulating miR-4262/ZEB1 axis, representing a prospective targeted therapy for cervical cancer.
Keywords: CRNDE, miR-4262, ZEB1, wnt/β-catenin pathway, cervical cancer