Four Departments of General Surgery, The First Affiliated Hospital of Jiamusi Medical University, Jiamusi, Heilongjiang, China.
Cell Biol Int. 2022 Dec;46(12):2107-2117. doi: 10.1002/cbin.11905. Epub 2022 Oct 6.
Oxaliplatin (L-OHP) is a standard treatment drug for colorectal cancer (CRC), but acquired drug resistance limits the outcome of patients. We investigated the involvement of sirtuin 1 (SIRT1) in L-OHP resistance in the setting of CRC via microRNA-20b-3p/DEP domain containing 1 (miR-20b-3p/DEPDC1) axis. CRC tissues that were resistant or sensitive to L-OHP were harvested, in which SIRT1, miR-20b-3p, and DEPDC1 levels were tested. L-OHP-resistant-resistant CRC cells were transfected, subsequently, cellular proliferation, invasion, migration, and apoptosis were tested, and tumor resistance to L-OHP was observed. The binding of SIRT1 to miR-20b-3p promoter and the targeting relationship between miR-20b-3p and DEPDC1 were verified. An aberrant elevation in SIRT1 expression was seen in L-OHP-resistant CRC tissues and cells. Knockdown of SIRT1 sensitized CRC cells and xenografted CRC tumors to L-OHP. SIRT1 bound with miR-20b-3p promoter to regulate DEPDC1. Reducing miR-20b-3p or raising DEPDC1 levels weakened the effect of SIRT1 knockdown on L-OHP-resistant-CRC cells. SIRT1 enhances L-OHP resistance in CRC by mediating miR-20b-3p/DEPDC1 axis.
奥沙利铂（L-OHP）是结直肠癌（CRC）的标准治疗药物，但获得性耐药限制了患者的预后。我们通过 microRNA-20b-3p/DEP 结构域包含 1（miR-20b-3p/DEPDC1）轴研究了 SIRT1 在 CRC 中 L-OHP 耐药中的作用。采集对 L-OHP 耐药或敏感的 CRC 组织，检测 SIRT1、miR-20b-3p 和 DEPDC1 水平。转染 L-OHP 耐药的 CRC 细胞，随后检测细胞增殖、侵袭、迁移和凋亡，并观察肿瘤对 L-OHP 的耐药性。验证了 SIRT1 与 miR-20b-3p 启动子的结合以及 miR-20b-3p 与 DEPDC1 的靶向关系。在 L-OHP 耐药的 CRC 组织和细胞中观察到 SIRT1 表达异常升高。敲低 SIRT1 可使 CRC 细胞和异种移植 CRC 肿瘤对 L-OHP 敏感。SIRT1 与 miR-20b-3p 启动子结合以调节 DEPDC1。降低 miR-20b-3p 或提高 DEPDC1 水平减弱了 SIRT1 敲低对 L-OHP 耐药-CRC 细胞的作用。SIRT1 通过介导 miR-20b-3p/DEPDC1 轴增强 CRC 对 L-OHP 的耐药性。
