The online version of this article (https://doi.org/10.1186/s13046-018-0684-8) contains supplementary material, which is available to authorized users.
Yongcan Xu, Xiang Yu and Chenchen Wei contributed equally to this work.
Yongcan Xu, Xiang Yu and Chenchen Wei are joint first authors.
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.
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.
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.
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.
Additional file 1: Table S1. Primer, siRNA and shRNA sequence, and antibodies information. (XLS 55 kb)13046_2018_684_MOESM1_ESM.xls
Additional file 2: Table S2. Pseudogenes profiling in gastric cancer from four GEO datasets. (XLSX 61 kb)13046_2018_684_MOESM2_ESM.xlsx
Additional file 3: Table S3. Correlation between DUXAP10 expression and clinicopathological characteristics of gastric cancer patients (n = 64). (DOC 38 kb)13046_2018_684_MOESM3_ESM.doc
Additional file 4: Table S4. Univariate and multivariate analysis of over-survival in gastric cancer patients (n = 64). (DOC 38 kb)13046_2018_684_MOESM4_ESM.doc
Additional file 5: Figure S1. (a, b) Analysis of the pseudogene DUXAP10 expression levels in BGC823, SGC7901, and MGC803 cells after transfection with DUXAP10 siRNAs or shRNAs by qPCR. (c) Analysis of DUXAP10 expression levels in AGS cells after transfection with DUXAP10 over-expression vector. (d, e) EdU incorporation and colony formation assays were performed to evaluate the effect of DUXAP10 over-expression on AGS cells proliferation. *P < 0.05 and **P < 0.01 (TIFF 9825 kb)13046_2018_684_MOESM5_ESM.tif
Additional file 6: Figure S2. (a) Analysis of DUXAP10 expression levels in tumor tissues collected from sh-DUXAP10 group and control group mice by qPCR. (b) Statistical analysis of E-cadherin, N-cadherin, Vimentin and β-catenin protein levels in DUXAP10 or negative control siRNAs transfected cells. *P < 0.05 and **P < 0.01 (TIFF 4831 kb)13046_2018_684_MOESM6_ESM.tif
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- Over-expression of oncigenic pesudogene DUXAP10 promotes cell proliferation and invasion by regulating LATS1 and β-catenin in gastric cancer
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