miR-133a 通过调节 LASP1 和 TGF-β/Smad3 信号通路在肺癌进展中发挥肿瘤抑制作用。

MiR-133a acts as a tumor suppressor in lung cancer progression by regulating the LASP1 and TGF-β/Smad3 signaling pathway.

机构信息

Department of Respiratory Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.

Department of Respiratory Medicine, Shan Dong Chest Hospital, Jinan, China.

出版信息

Thorac Cancer. 2020 Dec;11(12):3473-3481. doi: 10.1111/1759-7714.13678. Epub 2020 Oct 19.

BACKGROUND

MiR-133a has been confirmed to be involved in the development of multiple cancers including non-small cell lung cancer (NSCLC). However, the precise molecular mechanism has not yet been fully elucidated. The purpose of this study was to investigate the functional role and underlying mechanism of miR-133a in the progression of NSCLC.

METHODS

Quantitative real-time PCR (qRT-PCR) was performed to measure miR-133a and LASP1 expression in NSCLC tissues and cells. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to detect cell viability. The protein levels were measured by western blot. The tumor growth was measured by xenograft tumor formation assay.

RESULTS

miR-133a was significantly decreased while LASP1 was increased in NSCLC tissues and cells compared with control groups. Moreover, overexpression of miR-133a suppressed cell viability, whereas miR-133a knockdown enhanced the viability of A549 cells. More importantly, LASP1 was verified as a direct target of miR-133a. Moreover, overexpression of miR-133a inhibited the epithelial-mesenchymal transition (EMT) and TGF-β/Smad3 pathways by regulating LASP1 in vitro. In addition, miR-133a mimic suppressed tumor growth by modulating the TGF-β/Smad3 pathway in vivo.

CONCLUSIONS

In conclusion, miR-133a acted as a tumor suppressor in lung cancer progression by regulating the LASP1 and TGF-β/Smad3 signaling pathway.

背景

miR-133a 已被证实参与多种癌症的发展，包括非小细胞肺癌（NSCLC）。然而，其确切的分子机制尚未完全阐明。本研究旨在探讨 miR-133a 在 NSCLC 进展中的功能作用及其潜在机制。

方法

采用实时定量 PCR（qRT-PCR）检测 NSCLC 组织和细胞中 miR-133a 和 LASP1 的表达。3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四唑溴盐（MTT）法检测细胞活力。Western blot 法检测蛋白水平。通过异种移植肿瘤形成实验测量肿瘤生长。

结果

与对照组相比，miR-133a 在 NSCLC 组织和细胞中表达显著下调，而 LASP1 表达上调。此外，过表达 miR-133a 抑制 A549 细胞活力，而 miR-133a 敲低则增强 A549 细胞活力。更重要的是，LASP1 被证实是 miR-133a 的直接靶标。此外，miR-133a 通过调节 LASP1 在体外抑制上皮-间充质转化（EMT）和 TGF-β/Smad3 通路。此外，miR-133a 模拟物通过调节体内 TGF-β/Smad3 通路抑制肿瘤生长。