RGMB-AS1/ miR-4428/ PBX1 axis drives the progression of cervical cancer

Chenge Shen; Beixi Wang; Kaiwen Zhang; Ce Wang; Jiajia Wang; Zhanglu An; Lisha Shu

doi:10.21037/tcr.2020.04.19

RGMB-AS1/ miR-4428/ PBX1 axis drives the progression of cervical cancer

Transl Cancer Res. 2020 May;9(5):3180-3190. doi: 10.21037/tcr.2020.04.19.

Authors

Chenge Shen¹, Beixi Wang², Kaiwen Zhang³, Ce Wang⁴, Jiajia Wang⁵, Zhanglu An¹, Lisha Shu⁶

Affiliations

¹ Department of Obstetrics and Gynecology, Hebei North University, Zhangjiakou 075000, China.
² Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China.
³ Department of Obstetrics and Gynecology, Zhengzhou University, Zhengzhou 450000, China.
⁴ Department of Human Anatomy and Histology and Embryology, Hebei North University, Zhangjiakou 075000, China.
⁵ Department of Pathology, Hebei North University, Zhangjiakou 075000, China.
⁶ Department of Obstetrics and Gynecology, the First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China.

Abstract

Background: RGMB antisense RNA 1 (RGMB-AS1) is a member of long non-coding RNAs (lncRNAs) and relates to the carcinogenesis of numerous cancers. Nonetheless, its performance and mechanism in cervical cancer (CC) is unclear.

Methods: The expressions of RGMB-AS1, microRNA-4428 (miR-4428), PBX homeobox 1 (PBX1) were analyzed by quantitative real-time PCR (qRT-PCR). Nuclear-cytoplasmic fractionation was used to locate RGMB-AS1. Cell counting kit-8 (CCK-8), EdU, TUNEL, Western blot and transwell assays were performed to assess RGMB-AS1 function in proliferation, apoptosis, and invasion in vitro. Interplays involving miR-4428, RGMB-AS1 and PBX1 were verified applying luciferase reporter, RNA pull-down and RNA immunoprecipitation (RIP).

Results: RGMB-AS1 level was high in CC specimens and cells. RGMB-AS1 encouraged proliferation, and invasion, and depressed apoptosis in CC cells. Further, miR-4428 was screened as a targeted for RGMB-AS1, and RGMB-AS1 performed the competitive endogenous RNA (ceRNA) role to release PBX1 from miR-4428. Correlation analysis based on clinical specimens confirmed positive association between RGMB-AS1 and PBX1 and negative association of miR-4428 with RGMB-AS1 and PBX1. Rescue experiments indicated that PBX1 overexpression counteracted RGMB-AS1 silence-caused inhibition on CC development.

Conclusions: RGMB-AS1 regulated miR-4428/PBX1 axis to aggravate CC development, indicating that targeting RGMB-AS1 could be a potent way for developing the novel therapeutic methods for CC patients.

Keywords: PBX homeobox 1 (PBX1); RGMB antisense RNA 1 (RGMB-AS1); cervical cancer (CC); microRNA-4428 (miR-4428).