Suppression of pseudogene MT2P1 transcription induced by E2F7 inhibits hepatocellular carcinoma cell proliferation and facilitates apoptosis via preserving its parental gene.
Yiquan Lu, Yifan Zhang, Fengjie Hao, Nan Wang, Yongjun Chen, Junqing Wang
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引用次数: 0
Abstract
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.
期刊介绍：
Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.
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