| Title | p16 promotes proliferation in cervical carcinoma cells through CDK6-HuR-IL1A axis |
| Authors | Li, Mingzhe Yang, Jiong Liu, Kaiyu Yang, Jianming Zhan, Xiangwen Wang, Le Shen, Xiaomeng Chen, Jing Mao, Zebin |
| Affiliation | Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing, Peoples R China Peking Univ, Hosp 3, Dept Gastroenterol, Beijing, Peoples R China Tianjin Med Univ, Sch Basic Med Sci, Dept Immunol, Tianjin, Peoples R China |
| Keywords | TUMOR-SUPPRESSOR P16(INK4A) CYCLIN-DEPENDENT KINASES AU-RICH ELEMENTS INSERTION/DELETION POLYMORPHISM STRUCTURAL-CHARACTERIZATION HUR CDK6 RISK REPRESSION EXPRESSION |
| Issue Date | 2020 |
| Publisher | JOURNAL OF CANCER |
| Abstract | The Cyclin-Dependent Kinase Inhibitor p16 (p16) acts as a tumor suppressor in most cells, but for HPV transformed cervical cancer, in which oncoprotein E7 expressed by human papillomavirus (HPV) mediates the degradation of retinoblastoma protein (Rb), p16 exhibits oncogenic activity. Our study was conducted to study the mechanism underling p16 mediated promoting effect of cell proliferation in cervical cancer cell lines. CCK8 assay and EdU incorporation were conducted to evaluate cell proliferation. Loss-of-function assay was used to silence p16 in Ca Ski and SiHa cells. Next, western blot, qPCR, RNA silencing, luciferase activity assay, run-on assay, mRNA stability assay, RNA immunoprecipitation, co-immunoprecipitation Immunofluorescence were performed to examine the interaction between CDK6, HuR, and IL1A mRNA in p16 mediated proliferation promoting effect. Our results showed that: (1) Silencing p16 inhibited the proliferation of cervical cancer cells by decreasing the half-life of IL1A mRNA in CDK6 dependent manner; (2) The stabilization of IL1A mRNA was regulated by HuR which could be inactivated by p16/CDK6 mediated phosphorylation at Ser202; (3) IL1A mediated the oncogenic activity of p16 in cervical carcinoma cell lines. In conclusion, p16 promotes proliferation in cervical carcinoma cells through CDK6-HuR-IL1A axis. |
| URI | http://hdl.handle.net/20.500.11897/586026 |
| ISSN | 1837-9664 |
| DOI | 10.7150/jca.35479 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 |
