Division of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine, Renji Hospital, Shanghai, China.
FEBS Lett. 2011 Nov 16;585(22):3560-8. doi: 10.1016/j.febslet.2011.10.021. Epub 2011 Oct 22.
Chemotherapeutic drug resistance remains a major obstacle to the successful treatment of colon cancer. Here, we show that 77 differentially expressed miRNAs were identified in SW1116/HCPT versus SW1116, and over-expressed miR-506 in SW1116/HCPT cells was validated. Then it was indicated that PPARα is a common target of miR-506 by using a luciferase reporter assay. Our results also demonstrated that cytotoxic ability of HCPT requires the concomitant presence of PPARα, and that loss of PPARα expression imparts resistance to HCPTs anti-tumor effects. All together, our studies indicate that miR-506 over-expression in established HCPT-resistant colon cancer cell line confers resistance to HCPT by inhibiting PPARα expression, then providing a rationale for the development of miRNA-based strategies for reversing resistance in HCPT-resistant colon cancer cells.
化疗药物耐药性仍然是结肠癌成功治疗的主要障碍。在这里，我们发现 SW1116/HCPT 与 SW1116 相比有 77 个差异表达的 miRNA，并且在 SW1116/HCPT 细胞中验证了过表达的 miR-506。然后通过荧光素酶报告基因检测表明 PPARα 是 miR-506 的共同靶标。我们的结果还表明，HCPT 的细胞毒性能力需要同时存在 PPARα，并且 PPARα 表达的缺失赋予了对 HCPTs 抗肿瘤作用的耐药性。总之，我们的研究表明，在已建立的 HCPT 耐药结肠癌细胞系中过表达 miR-506 通过抑制 PPARα 表达赋予对 HCPT 的耐药性，从而为开发基于 miRNA 的策略提供了依据，以逆转 HCPT 耐药结肠癌细胞的耐药性。
