miR-330调控TAp73α介导的结直肠癌细胞HCT116对顺铂的敏感性

TAp73α-mediated cisplatin sensitivity was suppressed by miR-330 in colorectal cancer cell HCT116

摘要:

p73是p53基因家族中的一员，参与了细胞周期进程、凋亡和肿瘤耐药性等过程的调控.我们发现，在结肠癌细胞HCT116中，沉默p73可促进细胞对顺铂的敏感性，而且这种作用不依赖于p53.Hsa-miR-330 (miR-330)可直接抑制细胞内源性p73的表达并促进其对顺铂的敏感性.p73则可拮抗miR-330诱导的顺铂敏感性.我们的结果表明了p73对细胞顺铂敏感性的调控作用，为治疗顺铂抗性的肿瘤细胞提供了一条新途径.

Abstract:

The p53 family member p73 is a transcription factor involved in the regulation of cell cycle, apoptosis and cancer cell drug-resistant. Here we reported that knockdown of p73 sensitized HCT116 colorectal cancer cells to cisplatin treatment independent of p53. Hsa-miR-330 (miR-330) was identified to be able to directly repress the expression of TAp73α. Overexpression of miR-330 decreased the protein levels of endogenous TAp73α and phenocopied the effect of p73 knockdown. Restoration of TAp73α eliminated miR-330-induced chemosensitivity toward cisplatin. Our results demonstrated a novel function of TAp73α to impair cisplatin sensitivity in colorectal cancer cells which can be repressed by miR-330, thus provided an effective strategy for therapeutic treatment of cisplatin-resistant cancer cells.