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

RGMB-AS1/ miR-4428/ PBX1 轴驱动宫颈癌进展

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作者:Chenge Shen, Beixi Wang, Kaiwen Zhang, Ce Wang, Jiajia Wang, Zhanglu An, Lisha Shu

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.

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.

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.

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