ERCC6L, a DNA helicase, is involved in cell proliferation and associated with survival and progress in breast and kidney cancers.
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.
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650223, China.|KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China.
Shao-Yan
SY
Pu
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650223, China.|KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
Qin
Q
Yu
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650223, China.|KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
Huan
H
Wu
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650223, China.|KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
Jian-Jun
JJ
Jiang
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650223, China.|KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China.
Xiao-Qiong
XQ
Chen
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650223, China.|KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China.
Yong-Han
YH
He
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650223, China.|KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China.
Qing-Peng
QP
Kong
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004265:DNA Helicases / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
C484190:RAB31 protein, human; D020928:Mitogen-Activated Protein Kinases; D004265:DNA Helicases; C516980:ERCC6L protein, human; D020691:rab GTP-Binding Proteins
MAPK; cancer; excision repair cross-complementation group 6 like; proliferation