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Retracted : Carcinogenic role of K‐Ras‐ERK1/2 signaling in bladder cancer via inhibition of H1.2 phosphorylation at T146
Author(s) -
Fan Li,
Wang Yao,
Wang Weihua,
Wei Xin
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28716
Subject(s) - microbiology and biotechnology , mapk/erk pathway , phosphorylation , biology , kinase , signal transduction , anti apoptotic ras signalling cascade , cancer research
It has been reported that Ras‐ERK signaling regulated tumor suppressive genes via epigenetic mechanisms. Herein, we set out to investigate the correlation between K‐Ras‐ERK1/2 signaling and H1.2 phosphorylation, to provide a better understanding of K‐Ras‐ERK signaling in cancer. A plasmid for expression of mutated K‐Ras was transfected into human bladder carcinoma HT1197 cells. Western blot was carried out for testing the expression changes of ERK1/2 and H1.2. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay, soft‐agar colony formation assay, and transwell assay were used to test the effects of H1.2 phosphorylation at T146 (H1.2 T146ph ) on HT1197 cells growth and migration. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) and chromatin immunoprecipitation (ChIP) were performed to test whether H1.2 T146ph regulated K‐Ras‐ERK1/2 downstream genes. Furthermore, how K‐Ras‐ERK1/2 regulated H1.2 T146ph expression was studied. We found that the ERK1/2 was activated when K‐Ras was mutated, and H1.2 T146ph expression was significantly downregulated by K‐Ras mutation. H1.2 T146E for mimicking H1.2 T146ph significantly attenuated K‐Ras mutation induced increases in HT1197 cells viability, colony formation, and relative migration. Besides, H1.2 T146ph regulated the transcription of K‐Ras‐ERK1/2 downstream genes, including NT5E , GDF15 , CARD16 , CYR61 , IGFBP3 , and WNT16B . Furthermore, K‐Ras‐ERK1/2 signaling inhibited H1.2 phosphorylation at T146 through degradation of DNA‐PK, and the degraded DNA‐PK by K‐Ras‐ERK1/2 possibly via modulation of MDM2. In conclusion, the activation of K‐Ras‐ERK1/2 signaling will repress the phosphorylation of H1.2 at T146, and thereby, promoted the growth and migration of bladder cancer cells. K‐Ras‐ERK1/2 signaling repressed H1.2 phosphorylation possibly by MDM2‐mediated degradation of DNA‐PK.