TET1 suppresses colon cancer proliferation by impairing β‐catenin signal pathway

Abstract

The function of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) in cancer is background dependent and may be involved in the initial step of active DNA demethylation, while there is little research to decipher the role of TET1 in DNA methylation-sensitive colon cancer. Downregulated TET1 expression assayed by quantitative real-time PCR (qRT-PCR) was observed in both colon cancer samples and cancer cell lines of HT29, HCT116, and SW48. Such downregulation could promote colon cancer cells proliferation as indicated by the fact that shTET1 could increase the viability of HT29 and HCT116 cells determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide and cell count assay accompanied with upregulation of β-catenin (CTNNB1) and WNT luciferase activity, which was further confirmed as shTET1 could increase the tumor volume and tumor weight, and decrease the body weight in HT29 cells inoculated BALB/C nude mice. The CTNNB1 transfection could rescue the cell growth diminished by normal expression of TET1. shTET1 could promote axis inhibition protein1 (AXIN1) expression and the cell proliferation effect induced by TET1 short hairpin RNA was attenuated by co-inhibition of AXIN1. All of these indicate that TET1 can suppress colon cancer proliferation and the inhibition of the β-catenin pathway is AXIN1 dependent. K E Y W O R D Saxis inhibition protein1 (AXIN1), colon cancer, demethylation, ten-eleven translocation methylcytosine dioxygenase 1 (TET1), β-catenin

<p>Chrysin Induced Cell Apoptosis and Inhibited Invasion Through Regulation of TET1 Expression in Gastric Cancer Cells</p>

“…21 More recently, a study also indicated that TET1 overexpression was considerably associated with cell proliferation in colon cancer cells. 22 Correspondingly, our results also indicated that overexpression of TET1 inhibited cell growth of GC cells. Besides, overexpression of TET1 also inhibited cell migration and invasive capabilities of GC cells, consistent with previous results in hepatocellular carcinoma.…”

Hydroxyurea promotes TET1 expression and induces apoptosis in osteosarcoma cells

“…TET3 regulates the proliferation of HepG2 cells [26]. Compared with hepatocellular carcinoma, our results indicated that increased TET1 expression induced apoptosis and inhibited the growth of U2OS cells, consistent with previous data obtained from colon cancer cells [27]. TET1 expression was recently reported to be associated with apoptosis in bladder cancer cells [28].…”

Epigenetic silencing of TET1 mediated hydroxymethylation of base excision repair pathway during lung carcinogenesis

“…Accumulating evidence has discovered that TET1 played important roles in the occurrence and development of neoplastic diseases [23,24]. It has reported that overexpression of TET1 could signi cantly inhibit cell growth, migration and invasion of colon cancer and cervical cancer [23,25,26]. In addition, the recent study also found that TET1 involved in p53 mediated lung cancer cellular aging as an oncogene [27].…”