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Research Paper|Volume 14, Issue 19|pp 7906—7925

Pseudogene UBE2MP1 derived transcript enhances in vitro cell proliferation and apoptosis resistance of hepatocellular carcinoma cells through miR-145-5p/RGS3 axis

Fengjie Hao1, Nan Wang1, Honglian Gui2, Yifan Zhang1, Zhiyuan Wu3, Junqing Wang1
  • 1Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China
  • 2Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China
  • 3Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China
* Co-first author
Received: May 13, 2022Accepted: September 5, 2022Published: October 7, 2022

Copyright: © 2022 Hao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Pseudogenes are barely transcribed at normal, while the anomalous transcripts of them are mostly regarded as long non-coding RNAs (lncRNAs), which play potential functions in human tumorigenicity and development. The exact effects of pseudogene-derived transcripts on hepatocellular carcinoma (HCC) are ambiguous. According to our previous research and constructed database on the HCC-related lncRNAs, we noticed that UBE2MP1 was transcriptionally activated in HCC as a pseudogene from the ubiquitin-conjugating enzyme member UBE2M. In this study, we validated the high expression of the UBE2MP1 transcript in HCC and its adverse correlation with dismal outcomes for the patients. UBE2MP1 depletion at the transcript level significantly impaired cell proliferation and apoptosis resistance in HCC cell lines. Notably, we discovered that the UBE2MP1 transcript shared a specific sequence, binding to the miR-145-5p seed region with a typical ceRNA effect. Simultaneously, we verified an axis of miR-145-5p/RGS3 in HCC cells, which promoted cell proliferation and apoptosis resistance with significance. And modulation of UE2MP1 could remarkably affect RGS3 expression and consequentially influence HCC cell growth in vitro. And combined with the rescue experiment modulating either miR-145-5p or RGS3 furtherly indicated UBE2MP1 as an upstream regulator of the axis in promoting HCC cell growth and maintenance. Thus, our findings provide new strategies for HCC prevention and individual treatment.