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microRNA-29b 通过靶向 FOLR1 抑制结肠癌细胞生长并增加奥沙利铂敏感性。

microRNA-29b inhibits cell growth and promotes sensitivity to oxaliplatin in colon cancer by targeting FOLR1.

机构信息

Department of General Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Biofactors. 2020 Jan;46(1):136-145. doi: 10.1002/biof.1579. Epub 2019 Oct 17.

Abstract

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.

摘要

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。在人结肠癌组织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 的小干扰 (siRNA) (si-FOLR1) 或相应的阴性对照 (NC) 转染 SW480 和 SW620 结肠癌细胞系,然后在有或没有奥沙利铂 (L-OHP) 的情况下孵育。之后,分析细胞活力、细胞毒性、细胞凋亡以及 FOLR1、ATP 结合盒亚家族 G 成员 2 (ABCG2) 和 p-糖蛋白 (p-gp) 的表达。我们发现,与非肿瘤样本和非致瘤性永生化人结肠上皮细胞系 FHC 相比,结肠癌样本和细胞系中 miR-29b 显著降低,而 FOLR1 统计学上升高。miR-29b 的过表达显著抑制细胞活力,增加对 L-OHP 的敏感性,刺激细胞凋亡(均 p <.05),降低癌细胞中 ABCG2 和 p-gp 的水平,而抑制 miR-29b 则显示出相反的结果。此外,我们观察到 FOLR1 是 miR-29b 的直接靶标,并受 miR-29b 的负调控。此外,研究结果表明,FOLR1 抑制对细胞活力、对 L-OHP 的敏感性、细胞凋亡以及 ABCG2 和 p-gp 的水平的影响与 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增加对 L-OHP 的敏感性。

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