SETD5 regulates colon cancer cell migration and 5-FU sensitivity by mediating AKT1 phosphorylation
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Abstract:
Objective: To investigate the effect of SET domain-containing 5 (SETD5) on the proliferation, migration and 5-fluorouracil (5-FU) drug sensitivity of colon cancer cells and its mechanism. Methods: Colon cancer cells were cultured routinely, and siSETD5-NC and si-SETD5-1-3 plasmids were transfected into HT-29 cells with Lipofectamine 2000. The cells were divided into the control group (untreated), the si-SETD5-NC group, the si-SETD5 group and the si-SETD5+SC79 group. The HT-29 cells in the si-SETD5+SC79 group were transfected with plasmids and treated simultaneously with 10 μmol/L SC79. SETD5 mRNA expression in NCM460, HT-29 and LoVo cells was detected by qPCR. Flow cytometry, cell scratch method, WB method and CCK-8 method were used to detect the apoptosis, migration ability, expression of related proteins and sensitivity to 5-FU of HT-29 cells in each group, respectively. Results: SETD5 mRNA was highly expressed in both HT-29 and LoVo cells (both P<0.01). SETD5 mRNA was successfully knocked down in HT-29 cells (P<0.01). Knockdown of SETD5 mRNA could significantly inhibit the proliferation activity (P<0.01), migration ability (P<0.01), expression of related proteins (SETD5, p-PI3K, p-AKT1, p-mTOR protein) of HT-29 cells (all P<0.01), promote apoptosis (P<0.01), and increase the sensitivity to 5-FU (P<0.01). These effects could be partially blocked by AKT activator SC79 (P<0.05 or P<0.01). Conclusion: SETD5 is highly expressed in HT-29 and LoVo cells. SETD5 promotes the proliferation and migration of colon cancer HT-29 cells and reduces sensitivity to 5-FU through PI3K/AKT1 pathway. SETD5 is a potential target for clinical diagnosis and treatment of colon cancer.