长链非编码RNA MT1JP通过调控miR-92-3p在乳腺癌细胞中发挥抗癌作用。

Long non-coding RNA MT1JP exerts anti-cancer effects in breast cancer cells by regulating miR-92-3p.

作者信息

Wu Haiming, Li Sa

机构信息

Department of Breast Surgery, Shanxi provincial Cancer Hospital, Shanxi Medical University, Taiyuan, 030013, Shanxi, China.

出版信息

Gen Physiol Biophys. 2020 Jan;39(1):59-67. doi: 10.4149/gpb_2019039.

DOI:10.4149/gpb_2019039

PMID:32039825

Abstract

MT1JP is a LncRNA that is reportedly involved in gastric cancer development, but a biological role and mechanism for MT1JP in breast cancer is unknown. Quantitative RT-PCR was performed to detect the level of MT1JP and miR-92a-3p, and Western blotting assays ware performed to measure the expression of CDK2, cyclinE1, P21, CD151, CD147, MMP2 and MMP9 in breast cells. Subsequently, cell viability was analyzed with CCK-8 assay. Cell migration and invasion were analyzed with Transwell and Scratch Test, respectively. The results demonstrated that MT1JP was significantly down-regulated in breast cells. Additionally, we found that overexpression of MT1JP in breast cancer cells significantly inhibited cell proliferation, migration and invasion, and regulate the expression of CDK2, cyclinE1 and P21. We then investigated a possible mechanism for these results, MT1JP significantly inhibited CD151, CD147, MMP2 and MMP9 protein expression in breast cancer cells. Moreover, we found that MT1JP binds to and negatively regulates miR-92-3p, which is known to be an oncogene in some human cancers. Our data indicate that MT1JP functions as an anti-tumor LncRNA and downregulates miR-92-3p, CD151 and CD147, and may serve as a novel diagnostic and therapeutic marker in breast cancer.

摘要

MT1JP是一种长链非编码RNA（LncRNA），据报道它参与胃癌的发展，但MT1JP在乳腺癌中的生物学作用和机制尚不清楚。采用定量逆转录聚合酶链反应（qRT-PCR）检测MT1JP和miR-92a-3p的水平，采用蛋白质免疫印迹法检测乳腺癌细胞中细胞周期蛋白依赖性激酶2（CDK2）、细胞周期蛋白E1（cyclinE1）、P21、CD151、CD147、基质金属蛋白酶2（MMP2）和基质金属蛋白酶9（MMP9）的表达。随后，用细胞计数试剂盒-8（CCK-8）法分析细胞活力。分别用Transwell小室实验和划痕实验分析细胞迁移和侵袭能力。结果表明，MT1JP在乳腺癌细胞中显著下调。此外，我们发现MT1JP在乳腺癌细胞中的过表达显著抑制细胞增殖、迁移和侵袭，并调节CDK2、cyclinE1和P21的表达。然后，我们研究了这些结果的可能机制，MT1JP显著抑制乳腺癌细胞中CD151、CD147、MMP2和MMP9蛋白的表达。此外，我们发现MT1JP与miR-92-3p结合并对其起负调控作用，已知miR-92-3p在某些人类癌症中是一种癌基因。我们的数据表明，MT1JP作为一种抗肿瘤LncRNA发挥作用，下调miR-92-3p、CD151和CD147，可能作为乳腺癌一种新的诊断和治疗标志物。