ERCC6L, a DNA helicase, is involved in cell proliferation and associated with survival and progress in breast and kidney cancers

// Shao-Yan Pu 1, 2, * , Qin Yu 1, 2, 3, * , Huan Wu 1, 2, 3 , Jian-Jun Jiang 1, 2, 3 , Xiao-Qiong Chen 1, 2 , Yong-Han He 1, 2 and Qing-Peng Kong 1, 2 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 * These authors have contributed equally to this work Correspondence to: Qing-Peng Kong, email: kongqp@mail.kiz.ac.cn Yong-Han He, email: heyonghan@mail.kiz.ac.cn Keywords: excision repair cross-complementation group 6 like, cancer, proliferation, MAPK Received: July 02, 2016 Accepted: January 16, 2017 Published: February 02, 2017 ABSTRACT 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.