Over-expression of oncigenic pesudogene DUXAP10 promotes cell proliferation and invasion by regulating LATS1 and β-catenin in gastric cancer
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 hu...
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BMC
2018-01-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | http://link.springer.com/article/10.1186/s13046-018-0684-8 |
| _version_ | 1819169388739166208 |
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| author | Yongcan Xu Xiang Yu Chenchen Wei Fengqi Nie Mingde Huang Ming Sun |
| author_facet | Yongcan Xu Xiang Yu Chenchen Wei Fengqi Nie Mingde Huang Ming Sun |
| author_sort | Yongcan Xu |
| collection | DOAJ |
| description | 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. |
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| format | Article |
| id | doaj.art-ab63a10c71054ad2956fc4cc2d862603 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-22T19:18:43Z |
| publishDate | 2018-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-ab63a10c71054ad2956fc4cc2d8626032022-12-21T18:15:26ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662018-01-0137111210.1186/s13046-018-0684-8Over-expression of oncigenic pesudogene DUXAP10 promotes cell proliferation and invasion by regulating LATS1 and β-catenin in gastric cancerYongcan Xu0Xiang Yu1Chenchen Wei2Fengqi Nie3Mingde Huang4Ming Sun5Department of General Surgery, Huzhou Central HospitalDepartment of General Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityDepartment of Oncology, Second Affiliated Hospital, Nanjing Medical UniversityDepartment of Oncology, Second Affiliated Hospital, Nanjing Medical UniversityDepartment of Oncology, Huai’an First People’s Hospital, Nanjing Medical UniversityDepartment of Bioinformatics and computational biology, UT MD Anderson Cancer CenterAbstract 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.http://link.springer.com/article/10.1186/s13046-018-0684-8PesudogeneDUXAP10Gastric cancerAggressive phenotypePrognostic biomarker |
| spellingShingle | Yongcan Xu Xiang Yu Chenchen Wei Fengqi Nie Mingde Huang Ming Sun 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 Pesudogene DUXAP10 Gastric cancer Aggressive phenotype Prognostic biomarker |
| title | Over-expression of oncigenic pesudogene DUXAP10 promotes cell proliferation and invasion by regulating LATS1 and β-catenin in gastric cancer |
| title_full | Over-expression of oncigenic pesudogene DUXAP10 promotes cell proliferation and invasion by regulating LATS1 and β-catenin in gastric cancer |
| title_fullStr | Over-expression of oncigenic pesudogene DUXAP10 promotes cell proliferation and invasion by regulating LATS1 and β-catenin in gastric cancer |
| title_full_unstemmed | Over-expression of oncigenic pesudogene DUXAP10 promotes cell proliferation and invasion by regulating LATS1 and β-catenin in gastric cancer |
| title_short | Over-expression of oncigenic pesudogene DUXAP10 promotes cell proliferation and invasion by regulating LATS1 and β-catenin in gastric cancer |
| title_sort | over expression of oncigenic pesudogene duxap10 promotes cell proliferation and invasion by regulating lats1 and β catenin in gastric cancer |
| topic | Pesudogene DUXAP10 Gastric cancer Aggressive phenotype Prognostic biomarker |
| url | http://link.springer.com/article/10.1186/s13046-018-0684-8 |
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