Loss of RDM1 enhances hepatocellular carcinoma progression via p53 and Ras/Raf/ERK pathways.
作者： Shi‐Lu Chen , Li‐Li Liu , Chun‐Hua Wang , Shi‐Xun Lu , Xia Yang
关键词:
摘要: Hepatocellular carcinoma (HCC), with its ineffective therapeutic options and poor prognosis, represents a global threat. In the present study, we show that RAD52 motif 1 (RDM1), key regulator of DNA double-strand break repair recombination, is downregulated in HCC tissues suppresses tumor growth. clinical samples, low expression RDM1 correlates larger size, differentiation, unfavorable survival. vitro vivo data demonstrate knockdown increases cell proliferation, colony formation, population at G2/M phase, whereas overexpression results opposite phenotypes. Mechanistically, binds to suppressor p53 enhances protein stability. presence p53, phosphorylation Raf ERK. Overexpression or treatment ERK inhibitor significantly abolishes proliferation induced by depletion RDM1. addition, methyltransferase-like 3 markedly induces N6-methyladenosine modification mRNA represses expression. Taken together, our study indicates functions as may be potential prognostic factor for HCC.
sci-hub.se 参考文章(44)
Sten Orrenius, Boris Zhivotovsky, Pierluigi Nicotera, Regulation of cell death: the calcium-apoptosis link. Nature Reviews Molecular Cell Biology. ,vol. 4, pp. 552- 565 ,(2003) , 10.1038/NRM1150
M E Shambaugh, F M Rottman, J A Bokar, D Polayes, A G Matera, Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA. ,vol. 3, pp. 1233- 1247 ,(1997)
Lili Zhang, Xiaoping Li, Lijun Zhao, Lifang Zhang, Guo Zhang, Jianliu Wang, Lihui Wei, Nongenomic effect of estrogen on the MAPK signaling pathway and calcium influx in endometrial carcinoma cells. Journal of Cellular Biochemistry. ,vol. 106, pp. 553- 562 ,(2009) , 10.1002/JCB.22017
G Can, B Akpinar, Y Baran, B Zhivotovsky, M Olsson, 5-Fluorouracil signaling through a calcium–calmodulin-dependent pathway is required for p53 activation and apoptosis in colon carcinoma cells Oncogene. ,vol. 32, pp. 4529- 4538 ,(2013) , 10.1038/ONC.2012.467
Seth B Coffelt, Karin E De Visser, None, Inflammation lights the way to metastasis Nature. ,vol. 507, pp. 48- 49 ,(2014) , 10.1038/NATURE13062
Patricia A.J. Muller, Karen H. Vousden, Mutant p53 in Cancer: New Functions and Therapeutic Opportunities Cancer Cell. ,vol. 25, pp. 304- 317 ,(2014) , 10.1016/J.CCR.2014.01.021
Yang Wang, Yue Li, Julia I. Toth, Matthew D. Petroski, Zhaolei Zhang, Jing Crystal Zhao, N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nature Cell Biology. ,vol. 16, pp. 191- 198 ,(2014) , 10.1038/NCB2902
Yosef Landesman, Frank Bringold, Diane D Milne, David W Meek, Modifications of p53 Protein and Accumulation of p21 and gadd45 mRNA in TGF-β1 Growth Inhibited Cells Cellular Signalling. ,vol. 9, pp. 291- 298 ,(1997) , 10.1016/S0898-6568(97)89890-7
Guoyi Wu, Linan Xu, Nan Lin, Bo Liu, UCN-01 induces S and G2/M cell cycle arrest through the p53/p21(waf1) or CHK2/CDC25C pathways and can suppress invasion in human hepatoma cell lines. BMC Cancer. ,vol. 13, pp. 167- 167 ,(2013) , 10.1186/1471-2407-13-167
Augusto Villanueva, Josep M. Llovet, Liver cancer in 2013: Mutational landscape of HCC—the end of the beginning Nature Reviews Clinical Oncology. ,vol. 11, pp. 73- 74 ,(2014) , 10.1038/NRCLINONC.2013.243