ERCC6L, a DNA helicase, is involved in cell proliferation and associated with survival and progress in breast and kidney cancers | |
Pu SY1,2; Yu Q1,2,3; He YH[*]1,2; Kong QP[*]1,2; Wu H1,2; Jiang JJ1,2,3; Chen XQ1,2,3 | |
刊名 | Oncotarget
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2017 | |
卷号 | **期号:**页码:published online |
关键词 | MAPK cancer excision repair cross-complementation group 6 like proliferation |
通讯作者 | kongqp@mail.kiz.ac.cn ; heyonghan@mail.kiz.ac.cn |
英文摘要 | By analyzing 4987 cancer transcriptomes from The Cancer Genome Atlas (TCGA), we identified that excision repair cross-complementation group 6 like (ERCC6L), a newly discovered DNA helicase, is highly expressed in 12 solid cancers. However, its role and mechanism in tumorigenesis are largely unknown. In this study, we found that ERCC6L silencing by small interring RNA (siRNA) or short hairpin RNA (shRNA) significantly inhibited the proliferation of breast (MCF-7, MDA-MB-231) and kidney cancer cells (786-0). Furthermore, ERCC6L silencing induced cell cycle arrest at G0/G1 phase without affecting apoptosis. We then performed RNA sequencing (RNA-seq) analysis after ERCC6L silencing and identified that RAB31 was markedly downregulated at both the transcriptional and translational levels. Its downstream protein, phosphorylated MAPK and CDK2 were also inhibited by ERCC6L silencing. The xenograft experiment showed that silencing of ERCC6L strikingly inhibited tumor growth from the 7th day after xenograft in nude mice. In addition, higher ERCC6L expression was found to be significantly associated with worse clinical survival in breast and kidney cancers. In conclusion, our results suggest that ERCC6L may stimulates cancer cell proliferation by promoting cell cycle through a way of RAB31-MAPK-CDK2, and it could be a potential biomarker for cancer prognosis and target for cancer treatment. |
收录类别 | SCI |
资助信息 | This work was supported by grants from the Chinese Academy of Sciences (KJZD-EW-L14 and QYZDB- SSW-SMC020), National Basic Research Program of China (2012CB518205), the National Natural Science Foundation of China (81272309, 31322029, 81500670 and 81671404), and grant from the Youth Innovation Promotion Association of Chinese Academy of Sciences (to Y.H.H). |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://159.226.149.26:8080/handle/152453/10841] ![]() |
专题 | 昆明动物研究所_分子人类学 昆明动物研究所_遗传资源与进化国家重点实验室 |
作者单位 | 1.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650223, China 2.KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China 3.Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China |
推荐引用方式 GB/T 7714 | Pu SY,Yu Q,He YH[*],et al. ERCC6L, a DNA helicase, is involved in cell proliferation and associated with survival and progress in breast and kidney cancers[J]. Oncotarget,2017,**(**):published online. |
APA | Pu SY.,Yu Q.,He YH[*].,Kong QP[*].,Wu H.,...&Chen XQ.(2017).ERCC6L, a DNA helicase, is involved in cell proliferation and associated with survival and progress in breast and kidney cancers.Oncotarget,**(**),published online. |
MLA | Pu SY,et al."ERCC6L, a DNA helicase, is involved in cell proliferation and associated with survival and progress in breast and kidney cancers".Oncotarget **.**(2017):published online. |
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