miR-152-3p 通过抑制 HMGA2 表达抑制 UMUC3 和 TCCSUP 膀胱癌细胞系的增殖、侵袭和自噬。

miR-152-3p Inhibits Proliferation, Invasion and Autophagy in UMUC3 and TCCSUP Bladder Cancer Cell Lines via Suppressing HMGA2 Expression.

机构信息

Department of Urology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China.

Department of Urology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China

出版信息

Ann Clin Lab Sci. 2023 Jul;53(4):607-618.

PMID:37625835

Abstract

OBJECTIVE

MicroRNAs have been reported to be involved in the regulation of tumor progression. This study investigated the role of miR-152-3p in bladder cancer development.

METHODS

A total of 67 bladder cancer cases were enrolled. miR-152-3p expression in bladder cancer tissues and cells were detected using quantitative reverse transcriptase polymerase chain reaction. Bladder cancer cells were transfected by miR-152-3p mimic and inhibitor to up-regulate and down-regulate miR-152-3p expression. After transfection, cell counting kit-8 assay, flow cytometry, Brdu staining assay, transwell experiment and wound healing assay were conducted to research the effect of miR-152-3p up-regulation/down-regulation on bladder cancer cell viability, apoptosis, proliferation, invasion and migration abilities. The expression of high-mobility group protein A2 (HMGA2) and autophagy-related proteins was researched using Western blot. The interaction between miR-152-3p and HMGA2 was explored by dual luciferase reporter gene assay.

RESULTS

Low miR-152-3p expression in tumor tissues bladder cancer patients was associated with poor prognosis. miR-152-3p expression was abnormally down-regulated in bladder cancer cells. miR-152-3p up-regulation inhibited viability, proliferation, invasion, migration but promoted apoptosis of bladder cancer cells. miR-152-3p down-regulation showed the opposite effects. miR-152-3p up-regulation suppressed the expression of Beclin 1 and LC3II/LC3I proteins in bladder cancer cells, but miR-152-3p down-regulation increased them. HMGA2 was target of miR-152-3p, which could be directly inhibited by miR-152-3p. HMGA2 up-regulation reversed the inhibitory effect of miR-152-3p on bladder cancer cell malignant phenotype.

CONCLUSION

miR-152-3p inhibited malignant phenotype of bladder cancer cell lines via suppressing HMGA2 expression.

摘要

目的

已有研究报道 microRNAs（miRNAs）参与肿瘤进展的调控。本研究旨在探讨 miR-152-3p 在膀胱癌发展中的作用。

方法

纳入 67 例膀胱癌病例。采用实时定量逆转录聚合酶链反应（qRT-PCR）检测膀胱癌组织和细胞中 miR-152-3p 的表达。用 miR-152-3p 模拟物和抑制剂转染膀胱癌细胞，上调和下调 miR-152-3p 的表达。转染后，通过细胞计数试剂盒-8（CCK-8） assay、流式细胞术、 Brdu 染色 assay、Transwell 实验和划痕愈合实验研究 miR-152-3p 上调/下调对膀胱癌细胞活力、凋亡、增殖、侵袭和迁移能力的影响。采用 Western blot 检测高迁移率族蛋白 A2（HMGA2）和自噬相关蛋白的表达。通过双荧光素酶报告基因实验探索 miR-152-3p 与 HMGA2 之间的相互作用。

结果

肿瘤组织中 miR-152-3p 低表达与膀胱癌患者预后不良有关。miR-152-3p 在膀胱癌细胞中表达异常下调。miR-152-3p 上调抑制膀胱癌细胞活力、增殖、侵袭和迁移，促进凋亡。miR-152-3p 下调则表现出相反的效果。miR-152-3p 上调抑制膀胱癌细胞中 Beclin 1 和 LC3II/LC3I 蛋白的表达，但 miR-152-3p 下调则增加了它们的表达。HMGA2 是 miR-152-3p 的靶基因，可被 miR-152-3p 直接抑制。HMGA2 的上调逆转了 miR-152-3p 对膀胱癌细胞恶性表型的抑制作用。