Pseudogene Promotes Cell Proliferation and Migration of Hepatocellular Carcinoma by Sponging MiR-490-5p to Induce BUB1 Expression

Overview

Journal Front Genet

Date 2020 Aug 28

PMID 32849765

Citations 17

Authors

Haiping Zhang

Kaiqiu Chu

Chunxi Zheng

Lisheng Ren

Runhua Tian

Affiliations

Soon will be listed here.

Abstract

Hepatocellular Carcinoma (HCC) currently remains one of the most lethal malignancies worldwide. Recently, long non-coding RNAs (lncRNAs) had been demonstrated to play a crucial role in the progression of multiple human cancers, including HCC. In this study, we found that lncRNA DUXAP8 was upregulated in tumor samples and served as an oncogene in HCC. Bioinformatics analysis showed that DUXAP8 was significantly associated with the regulation of centrosome organization, homologous recombination, meiotic cell cycle process, sister chromatid segregation, nuclear chromosome segregation, and RNA export from the nucleus. The knockdown of DUXAP8 significantly suppresses cell proliferation and the cell cycle but induces cell apoptosis in HCC. Mechanically, the present study showed that DUXAP8 serves as a sponge of MiR-490-5p to promote the expression of BUB1 in HCC. Although the underlying regulatory mechanisms of DUXAP8 in HCC require further investigation, this study, for the first time, showed that DUXAP8 can serve as a new therapeutic target for HCC.

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References

Xu L, Yu X, Wei B, Hui H, Sun Y, Dai J . Long non-coding RNA DUXAP8 regulates proliferation and invasion of esophageal squamous cell cancer. Eur Rev Med Pharmacol Sci. 2018; 22(9):2646-2652. DOI: 10.26355/eurrev_201805_14959. View

Piao J, Zhu L, Sun J, Li N, Dong B, Yang Y . High expression of CDK1 and BUB1 predicts poor prognosis of pancreatic ductal adenocarcinoma. Gene. 2019; 701:15-22. DOI: 10.1016/j.gene.2019.02.081. View

Liu X, Jiang J, Yu C, Wang Y, Sun Y, Tang J . Secular trends in incidence and mortality of bladder cancer in China, 1990-2017: A joinpoint and age-period-cohort analysis. Cancer Epidemiol. 2019; 61:95-103. DOI: 10.1016/j.canep.2019.05.011. View

Xu B, Xu T, Liu H, Min Q, Wang S, Song Q . MiR-490-5p Suppresses Cell Proliferation and Invasion by Targeting BUB1 in Hepatocellular Carcinoma Cells. Pharmacology. 2017; 100(5-6):269-282. DOI: 10.1159/000477667. View

Lin M, Hong Y, Zhang Y, Lin B, He X . Mechanism of lncRNA DUXAP8 in promoting proliferation of bladder cancer cells by regulating PTEN. Eur Rev Med Pharmacol Sci. 2018; 22(11):3370-3377. DOI: 10.26355/eurrev_201806_15158. View

Li Z, Zhang J, Liu X, Li S, Wang Q, Chen D . The LINC01138 drives malignancies via activating arginine methyltransferase 5 in hepatocellular carcinoma. Nat Commun. 2018; 9(1):1572. PMC: 5910401. DOI: 10.1038/s41467-018-04006-0. View

Fang Z, Li M, Zhang Y, Liu X . MiR-490-5p inhibits the metastasis of hepatocellular carcinoma by down-regulating E2F2 and ECT2. J Cell Biochem. 2018; 119(10):8317-8324. DOI: 10.1002/jcb.26876. View

Sun M, Nie F, Zang C, Wang Y, Hou J, Wei C . The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB. Mol Ther. 2017; 25(3):739-751. PMC: 5363203. DOI: 10.1016/j.ymthe.2016.12.018. View

Weidle U, Schmid D, Birzele F, Brinkmann U . MicroRNAs Involved in Metastasis of Hepatocellular Carcinoma: Target Candidates, Functionality and Efficacy in Animal Models and Prognostic Relevance. Cancer Genomics Proteomics. 2019; 17(1):1-21. PMC: 6937123. DOI: 10.21873/cgp.20163. View

10.

Huang T, Wang X, Yang X, Ji J, Wang Q, Yue X . Long Non-Coding RNA DUXAP8 Enhances Renal Cell Carcinoma Progression via Downregulating miR-126. Med Sci Monit. 2018; 24:7340-7347. PMC: 6198709. DOI: 10.12659/MSM.910054. View

11.

Qin G, Tu X, Li H, Cao P, Chen X, Song J . Long Noncoding RNA p53-Stabilizing and Activating RNA Promotes p53 Signaling by Inhibiting Heterogeneous Nuclear Ribonucleoprotein K deSUMOylation and Suppresses Hepatocellular Carcinoma. Hepatology. 2019; 71(1):112-129. DOI: 10.1002/hep.30793. View

12.

Ma H, Xie M, Sun M, Chen T, Jin R, Ma T . The pseudogene derived long noncoding RNA DUXAP8 promotes gastric cancer cell proliferation and migration via epigenetically silencing PLEKHO1 expression. Oncotarget. 2017; 8(32):52211-52224. PMC: 5581023. DOI: 10.18632/oncotarget.11075. View

13.

Chen W, Ye L, Wen D, Chen F . MiR-490-5p Inhibits Hepatocellular Carcinoma Cell Proliferation, Migration and Invasion by Directly Regulating ROBO1. Pathol Oncol Res. 2017; 25(1):1-9. DOI: 10.1007/s12253-017-0305-4. View

14.

Lettnin A, Wagner E, Carrett-Dias M, Dos Santos Machado K, Werhli A, Canedo A . Silencing the OCT4-PG1 pseudogene reduces OCT-4 protein levels and changes characteristics of the multidrug resistance phenotype in chronic myeloid leukemia. Mol Biol Rep. 2019; 46(2):1873-1884. DOI: 10.1007/s11033-019-04639-4. View

15.

Yang J, Hainaut P, Gores G, Amadou A, Plymoth A, Roberts L . A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019; 16(10):589-604. PMC: 6813818. DOI: 10.1038/s41575-019-0186-y. View

16.

Yang J, Roberts L . Hepatocellular carcinoma: A global view. Nat Rev Gastroenterol Hepatol. 2010; 7(8):448-58. PMC: 3926946. DOI: 10.1038/nrgastro.2010.100. View

17.

Lou W, Ding B, Fan W . High Expression of Pseudogene PTTG3P Indicates a Poor Prognosis in Human Breast Cancer. Mol Ther Oncolytics. 2019; 14:15-26. PMC: 6463746. DOI: 10.1016/j.omto.2019.03.006. View

18.

Lian Y, Yang J, Lian Y, Xiao C, Hu X, Xu H . DUXAP8, a pseudogene derived lncRNA, promotes growth of pancreatic carcinoma cells by epigenetically silencing CDKN1A and KLF2. Cancer Commun (Lond). 2018; 38(1):64. PMC: 6235391. DOI: 10.1186/s40880-018-0333-9. View

19.

Li L, Feng R, Fei S, Cao J, Zhu Q, Ji G . NANOGP8 expression regulates gastric cancer cell progression by transactivating DBC1 in gastric cancer MKN-45 cells. Oncol Lett. 2019; 17(1):555-563. PMC: 6313168. DOI: 10.3892/ol.2018.9595. View