The present study was aimed to explore the functional role of microRNA (miR)‐29b in colon cancer, as well as underlying mechanisms. Expressions of miR‐29b and folate receptor 1 (FOLR1) were measured in both human colon tumor samples and cell lines. Colon cancer cell lines SW480 and SW620 were transfected with miR‐29b mimic, antisense oligonucleotides (ASO)‐miR‐29b, small interfering (siRNA) against FOLR1 (si‐FOLR1), or corresponding negative controls (NCs), and then were incubated with or without oxaliplatin (L‐OHP). Thereafter, cell viability, cytotoxicity, cell apoptosis, and expression of FOLR1, ATP Binding Cassette Subfamily G Member 2 (ABCG2) and p‐glycoprotein (p‐gp) were analyzed. We found that miR‐29b was significantly decreased, while FOLR1 was statistically elevated in colon cancer samples and cell lines compared to the nontumor samples and nontumourigenic immortalized human colon epithelial cell line FHC. Overexpression of miR‐29b markedly inhibited cell viability, promoted sensitivity to L‐OHP, stimulated cell apoptosis (all p < .05), and decreased the levels of ABCG2 and p‐gp in cancer cells, whereas suppression of miR‐29b showed contrary results. Moreover, we observed that FOLR1 was a direct target of miR‐29b and was negatively regulated by miR‐29b. In addition, the findings revealed that the effects of FOLR1 inhibition on cell viability, sensitivity to L‐OHP, cell apoptosis, and the levels of ABCG2 and p‐gp were similar to overexpression of miR‐29b. Taken together, our study suggests that miR‐29b inhibits cell growth and promotes sensitivity to L‐OHP in colon cancer by targeting FOLR1.

中文翻译：

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microRNA-29b 通过靶向 FOLR1 抑制结肠癌中的细胞生长并提高对奥沙利铂的敏感性。

本研究旨在探讨 microRNA (miR)-29b 在结肠癌中的功能作用及其潜在机制。在人类结肠肿瘤样本和细胞系中测量了 miR-29b 和叶酸受体 1 (FOLR1) 的表达。用 miR-29b 模拟物、反义寡核苷酸 (ASO)-miR-29b、针对 FOLR1 (si-FOLR1) 的小干扰 (siRNA) 或相应的阴性对照 (NCs) 转染结肠癌细胞系 SW480 和 SW620，然后孵育有或没有奥沙利铂（L-OHP）。此后，分析了细胞活力、细胞毒性、细胞凋亡和 FOLR1、ATP 结合盒亚科 G 成员 2 (ABCG2) 和 p-糖蛋白 (p-gp) 的表达。我们发现 miR-29b 显着降低，而与非肿瘤样品和非致瘤性永生化人结肠上皮细胞系 FHC 相比，结肠癌样品和细胞系中的 FOLR1 在统计学上升高。miR-29b 的过表达显着抑制细胞活力，提高对 L-OHP 的敏感性，刺激细胞凋亡（所有p  < .05)，并降低癌细胞中 ABCG2 和 p-gp 的水平，而抑制 miR-29b 则显示相反的结果。此外，我们观察到 FOLR1 是 miR-29b 的直接靶标，并受到 miR-29b 的负调控。此外，研究结果表明，抑制 FOLR1 对细胞活力、对 L-OHP 的敏感性、细胞凋亡以及 ABCG2 和 p-gp 水平的影响与 miR-29b 的过表达相似。总之，我们的研究表明，miR-29b 通过靶向 FOLR1 抑制结肠癌中的细胞生长并提高对 L-OHP 的敏感性。