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UBE2MP1 假基因衍生的转录本通过 miR-145-5p/RGS3 轴增强肝癌细胞的增殖和抗凋亡能力。

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

机构信息

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.

Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.

出版信息

Aging (Albany NY). 2022 Oct 7;14(19):7906-7925. doi: 10.18632/aging.204319.

DOI:10.18632/aging.204319
PMID:36214767
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9596209/
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 . 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.

摘要

假基因在正常情况下几乎不转录,而它们的异常转录本大多被认为是长非编码 RNA(lncRNA),在人类肿瘤发生和发展中发挥潜在功能。假基因衍生的转录本对肝细胞癌(HCC)的确切影响尚不清楚。根据我们之前关于 HCC 相关 lncRNA 的研究和构建的数据库,我们注意到泛素结合酶成员 UBE2M 的假基因 UBE2MP1 在 HCC 中作为转录激活物。在这项研究中,我们验证了 HCC 中 UBE2MP1 转录本的高表达及其与患者预后不良的负相关。UBE2MP1 在转录本水平上的耗竭显着削弱了 HCC 细胞系的细胞增殖和抗凋亡能力。值得注意的是,我们发现 UBE2MP1 转录本具有特定的序列,与 miR-145-5p 的种子区域结合,具有典型的 ceRNA 效应。同时,我们在 HCC 细胞中验证了 miR-145-5p/RGS3 的轴,该轴具有重要的促进细胞增殖和抗凋亡能力。而 UBE2MP1 的调节可以显著影响 RGS3 的表达,从而影响 HCC 细胞的生长。并且通过调节 miR-145-5p 或 RGS3 的挽救实验进一步表明 UBE2MP1 作为促进 HCC 细胞生长和维持的轴的上游调节剂。因此,我们的研究结果为 HCC 的预防和个体化治疗提供了新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d9/9596209/028afb73cea2/aging-14-204319-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d9/9596209/028afb73cea2/aging-14-204319-g007.jpg
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