Lu Yiquan, Zhang Yifan, Hao Fengjie, Wang Nan, Chen Yongjun, Wang Junqing
Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Cancer Biol Ther. 2025 Dec;26(1):2510035. doi: 10.1080/15384047.2025.2510035. Epub 2025 May 23.
The majority of the pseudogenes are inert in normal transcription. Their transcripts are mostly attributed to non-coding RNAs that play various functions in human tumorigenicity and progression. Distinctively, pseudogene MT2P1 is universally transcribed in hepatocytes and presents a significant decrease in hepatocellular carcinoma (HCC). The effect of MT2P1-RNA on HCC cell proliferation and apoptosis needs investigation. MT2P1-RNA was detected by RT-qPCR assay in HCC tissues and cell lines, combined with the exploration of the public databases. The immunohistochemistry assay was used for testing the expression profile of E2F7 and the parental gene MT2A. The clinicopathological features of the patients were collected and analyzed. Ectopic expression of MT2P1-RNA in HCC cell lines was conducted, and the CCK8 assay and flow cytometry assay were carried out. Chromatin immunoprecipitation assay and Dual-luciferase reporter assay were, respectively, applied to validate the interaction between MT2P1, E2F7, and microRNA-15b-5p. The downregulation of MT2P1-RNA in HCC is negatively correlated with dismal clinicopathological features. MT2P1-RNA significantly suppressed HCC cell proliferation and induced apoptosis. E2F7 depletion sequentially elevated the level of MT2P1-RNA and MT2A, and E2F7 was validated as a suppressive transcription factor of the MT2P1 gene. The direct interactions of either MT2P1/miR-15b-5p or miR-15b-5p/MT2A were, respectively, ascertained, enlightening the ceRNA effect of them. The pseudogene-derived MT2P1-RNA is a suppressor of HCC by exerting the ceRNA effect on preserving MT2A, and its transcription is regulated by the suppressive transcription factor E2F7.
大多数假基因在正常转录中是无活性的。它们的转录本大多归因于在人类肿瘤发生和进展中发挥各种功能的非编码RNA。独特的是，假基因MT2P1在肝细胞中普遍转录，在肝细胞癌（HCC）中显著降低。MT2P1-RNA对HCC细胞增殖和凋亡的影响需要研究。通过RT-qPCR检测在HCC组织和细胞系中检测MT2P1-RNA，并结合公共数据库进行探索。免疫组织化学检测用于检测E2F7和亲本基因MT2A的表达谱。收集并分析患者的临床病理特征。在HCC细胞系中进行MT2P1-RNA的异位表达，并进行CCK8检测和流式细胞术检测。分别应用染色质免疫沉淀检测和双荧光素酶报告基因检测来验证MT2P1、E2F7和微小RNA-15b-5p之间的相互作用。HCC中MT2P1-RNA的下调与不良临床病理特征呈负相关。MT2P1-RNA显著抑制HCC细胞增殖并诱导凋亡。E2F7的缺失依次提高了MT2P1-RNA和MT2A的水平，并且E2F7被验证为MT2P1基因的抑制性转录因子。分别确定了MT2P1/miR-15b-5p或miR-15b-5p/MT2A的直接相互作用，揭示了它们的ceRNA效应。假基因衍生的MT2P1-RNA通过对MT2A发挥ceRNA效应而成为HCC的抑制剂，其转录受抑制性转录因子E2F7调控。
