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微小 RNA-106b 在前列腺癌中作为癌基因发挥作用,通过靶向 LARP4B 调节肿瘤活力和转移。

MicroRNA‑106b functions as an oncogene and regulates tumor viability and metastasis by targeting LARP4B in prostate cancer.

机构信息

Department of Urology, Ningbo First Hospital, Ningbo, Zhejiang 315010, P.R. China.

出版信息

Mol Med Rep. 2019 Aug;20(2):951-958. doi: 10.3892/mmr.2019.10343. Epub 2019 Jun 5.

DOI:10.3892/mmr.2019.10343
PMID:31173237
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6625195/
Abstract

Prostate cancer (PCa) is the most common malignancy among males worldwide, and is one of the leading causes of cancer‑related mortality. MicroRNAs (miRs) are a type of endogenous, noncoding RNA that serve a key role in pathological processes, and have been demonstrated to be involved in the formation and progression of PCa. Previous studies have reported that miR‑106b acts as an oncogene; however, the specific effects of miR‑106b on PCa have not been fully elucidated. The present study aimed to investigate the role and underlying molecular mechanisms of miR‑106b in the initiation and progression of PCa. In this study, miR‑106b was reported to be overexpressed and la‑related protein 4B (LARP4B) was downregulated in PCa tissues compared with paracancerous tissues. In addition, LARP4B was identified as a target gene of miR‑106b by bioinformatics prediction analysis and a dual luciferase reporter gene assay. Furthermore, MTT, wound healing and Transwell assays were performed to evaluate PCa cell viability, and migration and invasive abilities. The data revealed that inhibition of miR‑106b significantly suppressed the viability, migration and invasion of PCa cells. In addition, inhibition of miR‑106b significantly suppressed the mRNA and protein expression of cancer‑related genes, including matrix metalloproteinase‑2, cluster of differentiation 44 and Ki‑67, and increased that of the tumor suppressor, mothers against decapentaplegic homolog 2. Collectively, the findings of the present study indicated that miR‑106b may target LAR4B to inhibit cancer cell viability, migration and invasion, and may be considered as a novel therapeutic target in PCa.

摘要

前列腺癌(PCa)是全球男性中最常见的恶性肿瘤,也是癌症相关死亡的主要原因之一。microRNAs(miRs)是一种内源性非编码 RNA,在病理过程中发挥关键作用,并已被证明参与 PCa 的形成和进展。先前的研究报道 miR-106b 作为一种癌基因起作用;然而,miR-106b 对 PCa 的具体影响尚未完全阐明。本研究旨在探讨 miR-106b 在 PCa 发生和发展中的作用及其潜在的分子机制。在这项研究中,与癌旁组织相比,PCa 组织中 miR-106b 表达上调,LARP4B 下调。此外,通过生物信息学预测分析和双荧光素酶报告基因检测,证实 LARP4B 是 miR-106b 的靶基因。进一步通过 MTT、划痕愈合和 Transwell 实验评估 PCa 细胞活力、迁移和侵袭能力。结果显示,抑制 miR-106b 显著抑制了 PCa 细胞的活力、迁移和侵袭。此外,抑制 miR-106b 显著抑制了癌症相关基因,包括基质金属蛋白酶-2、CD44 和 Ki-67 的 mRNA 和蛋白表达,同时增加了肿瘤抑制因子,母亲抗 Decapentaplegic 同源物 2 的表达。综上所述,本研究结果表明,miR-106b 可能通过靶向 LAR4B 抑制癌细胞活力、迁移和侵袭,可作为 PCa 的一种新型治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c32/6625195/e5e04f26bf6b/MMR-20-02-0951-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c32/6625195/ef52ea4246ab/MMR-20-02-0951-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c32/6625195/2ca22a0cb233/MMR-20-02-0951-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c32/6625195/8c03677d31db/MMR-20-02-0951-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c32/6625195/7b9533d42520/MMR-20-02-0951-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c32/6625195/c446973a29be/MMR-20-02-0951-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c32/6625195/e5e04f26bf6b/MMR-20-02-0951-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c32/6625195/ef52ea4246ab/MMR-20-02-0951-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c32/6625195/2ca22a0cb233/MMR-20-02-0951-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c32/6625195/8c03677d31db/MMR-20-02-0951-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c32/6625195/7b9533d42520/MMR-20-02-0951-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c32/6625195/c446973a29be/MMR-20-02-0951-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c32/6625195/e5e04f26bf6b/MMR-20-02-0951-g05.jpg

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