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miR-145-5p 通过靶向 CDCA3 抑制结直肠癌细胞的增殖、转移和 EMT。

miR-145-5p suppresses proliferation, metastasis and EMT of colorectal cancer by targeting CDCA3.

机构信息

Department of Oncology, Jingjiang People's Hospital, Jingjiang, Jiangsu, 214504, PR China; Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, PR China.

Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, PR China.

出版信息

Pathol Res Pract. 2020 Apr;216(4):152872. doi: 10.1016/j.prp.2020.152872. Epub 2020 Feb 24.

Abstract

MicroRNAs play a critical role in regulating the carcinogenesis of colorectal cancer (CRC). Even though its role is unclear in CRC, miR-145-5p has been reported to have anti-oncogene properties in several tumors. Our research examined the function of miR-145-5p in CRC and the potential underlying mechanism. From the bioinformatics and qRT-PCR analysis, miR-145-5p levels were lower in CRC samples and cell lines. LoVo and SW480 cells were treated with miR-145-5p mimics and inhibitor, respectively. Cell cycle, CCK-8 and EdU assays revealed that overexpression of miR-145-5p suppressed cell viability and G1/S phase transition. Conversely, miR-145-5p inhibitor promoted cell growth and cell cycle transition. Elevated miR-145-5p expression also suppressed the migration, invasion and EMT of CRC cells, while miR-145-5p reduction had a reverse effect. CDCA3 was identified as a downstream effector of miR-145-5p and had a negative correlation with the miR-145-5p expression in CRC. In addition, co-transfection of miR-145-5p inhibitor and si-CDCA3 showed that CDCA3 in SW480 cells could reverse the effect caused by miR-145-5p. In conclusion, our findings demonstrated that miR-145-5p could act as a tumor suppressor in CRC by targeting CDCA3, and serve as a diagnostic and therapeutic biomarker of CRC.

摘要

微小 RNA 在调控结直肠癌(CRC)的致癌作用中起着关键作用。尽管 miR-145-5p 在 CRC 中的作用尚不清楚,但已有研究报道其在几种肿瘤中具有抑癌基因特性。我们的研究探讨了 miR-145-5p 在 CRC 中的功能及其潜在的作用机制。通过生物信息学和 qRT-PCR 分析,CRC 样本和细胞系中 miR-145-5p 的水平较低。分别用 miR-145-5p 模拟物和抑制剂处理 LoVo 和 SW480 细胞。细胞周期、CCK-8 和 EdU 检测表明,miR-145-5p 的过表达抑制了细胞活力和 G1/S 期转换。相反,miR-145-5p 抑制剂促进了细胞生长和细胞周期的转变。miR-145-5p 表达水平的升高还抑制了 CRC 细胞的迁移、侵袭和 EMT,而 miR-145-5p 的减少则产生了相反的效果。CDCA3 被鉴定为 miR-145-5p 的下游效应物,与 CRC 中 miR-145-5p 的表达呈负相关。此外,共转染 miR-145-5p 抑制剂和 si-CDCA3 表明,SW480 细胞中的 CDCA3 可以逆转 miR-145-5p 引起的作用。总之,我们的研究结果表明,miR-145-5p 可以通过靶向 CDCA3 作为 CRC 的肿瘤抑制因子发挥作用,并可作为 CRC 的诊断和治疗生物标志物。

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