Over-expression of oncigenic pesudogene DUXAP10 promotes cell proliferation and invasion by regulating LATS1 and β-catenin in gastric cancer

Journal of Experimental & Clinical Cancer Research

Ming Sun¹  Yongcan Xu²  Xiang Yu³  Mingde Huang⁴  Chenchen Wei⁵  Fengqi Nie⁵ 

[1] Department of Bioinformatics and computational biology, UT MD Anderson Cancer Center;Department of General Surgery, Huzhou Central Hospital;Department of General Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University;Department of Oncology, Huai’an First People’s Hospital, Nanjing Medical University;Department of Oncology, Second Affiliated Hospital, Nanjing Medical University;

关键词: Pesudogene;    DUXAP10;    Gastric cancer;    Aggressive phenotype;    Prognostic biomarker;   

DOI  :  10.1186/s13046-018-0684-8

来源: DOAJ

【 摘 要 】

Abstract Background Recently, the pesudogenes have emerged as critical regulators in human cancers tumorigenesis and progression, and been identified as a key revelation in post-genomic biology. However, the expression pattern, biological function and mechanisms responsible for these molecules in human gastric cancer (GC) are not fully understood. Methods In this study, we globally assessed the transcriptomic differences of pesudogenes in gastric cancer using publicly available microarray data. DUXAP10 expression levels in GC tissues and cells was detected using quantitative real-time PCR (qPCR). DUXAP10 siRNAs and over-expression vector were transfected into GC cells to down-regulate or up-regulate DUXAP10 expression. Loss- and gain-of function assays were performed to investigate the role of DUXAP10 in GC cells cell proliferation, and invasion. RIP, RNA pulldown, and ChIP assays were used to determine the mechanism of DUXAP10’s regulation of underlying targets. Results The pesudogene DUXAP10 is the only pseudogene that significantly over-expressed in all four GEO datasets, and frequently over-expressed in many other cancers including Liver Hepatocellular carcinoma, Bladder cancer, and Esophageal Cancer. High DUXAP10 expression is associated with GC patients poor prognosis, and knockdown of DUXAP10 significantly inhibits cells proliferation, migration and invasion in GC. Mechanistic investigation shows that DUXAP10 can interact with PRC2 and LSD1 to repress LATS1 expression at transcriptional level, and bind with HuR to maintain the stability of β-catenin mRNA and increase its protein levels at post-transcriptional level. Conclusions Overall, our findings illuminate how increased DUXAP10 confers an oncogenic function in GC development and progression that may serve as a candidate prognostic biomarker and target for clinical management of GC.

【 授权许可】

Unknown