长链非编码 RNA LINC00173 作为 miR-338-3p 的海绵体通过调节 Rab25 促进前列腺癌的进展。
Long non-coding RNA LINC00173 serves as sponge for miR-338-3p to promote prostate cancer progression via regulating Rab25.
机构信息
Department of Urology, the Suqian First Hospital, Suqian, Jiangsu, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 Sep;24(18):9290-9302. doi: 10.26355/eurrev_202009_23011.
OBJECTIVE
Long non-coding RNA LINC00173 (LINC00173) has been shown to facilitate the progression of a number of malignancies. In this study, we aimed to investigate the function of LINC00173 on prostate cancer (PCa) and discover the potential regulatory mechanism.
PATIENTS AND METHODS
RT-PCR was used to determine the levels of LINC00173, miR-338-3p and Rab25 in PCa patients and cell lines. The clinical significance of LINC00173 was statistically analyzed in 124 PCa patients. CCK-8, colony formation, transwell, scratch wound, Ethynyldeoxyuridine (EdU) assays and flow cytometry assays were used to detect the proliferation, apoptosis, invasion and migration of PCa cells. The mechanism of LINC00173 action was explored through bioinformatics, RNA pull-down assays and Luciferase reporter assays.
RESULTS
We observed that the expression of LINC00173 and Rab25 was distinctly upregulated in both PCa specimens and cell lines, while miR-338-3p expression was significantly down-regulated. High LINC00173 expression was associated with Gleason score, preoperative PSA level and reduced patient survivals. Functional assays revealed that knockdown of LINC00173 suppressed the proliferation, migration and invasion of PCa cells, and promoted apoptosis. Mechanistically, LINC00173 acted as a competitive endogenous RNA in PCa and increased Rab25 expressions via sponging miR-338-3p. Moreover, LINC00173 promoted PCa progression by interacting with miR-338-3p and Rab25.
CONCLUSIONS
Our findings, for the first time, identified a novel PCa-related lncRNA, LINC00173 which might serve as an oncogene in PCa. The discovery of the LINC00173/miR-338-3p/Rab25 pathways provided new thinking for the treatments of PCa.
目的
长链非编码 RNA LINC00173（LINC00173）已被证明可促进多种恶性肿瘤的进展。在这项研究中，我们旨在研究 LINC00173 对前列腺癌（PCa）的作用，并发现潜在的调节机制。
患者和方法
使用 RT-PCR 确定 PCa 患者和细胞系中 LINC00173、miR-338-3p 和 Rab25 的水平。在 124 名 PCa 患者中对 LINC00173 的临床意义进行了统计学分析。使用 CCK-8、集落形成、Transwell、划痕伤口、Ethynyldeoxyuridine（EdU）测定和流式细胞术测定来检测 PCa 细胞的增殖、凋亡、侵袭和迁移。通过生物信息学、RNA 下拉测定和荧光素酶报告测定来探索 LINC00173 作用的机制。
结果
我们观察到，LINC00173 和 Rab25 的表达在 PCa 标本和细胞系中均明显上调，而 miR-338-3p 的表达显著下调。高 LINC00173 表达与 Gleason 评分、术前 PSA 水平和降低的患者生存率相关。功能测定表明，敲低 LINC00173 可抑制 PCa 细胞的增殖、迁移和侵袭，并促进凋亡。在机制上，LINC00173 在 PCa 中作为竞争性内源性 RNA，通过海绵吸附 miR-338-3p 增加 Rab25 的表达。此外，LINC00173 通过与 miR-338-3p 和 Rab25 相互作用促进 PCa 的进展。
结论
我们的研究结果首次确定了一种新的与 PCa 相关的 lncRNA，LINC00173，它可能作为 PCa 的癌基因。LINC00173/miR-338-3p/Rab25 通路的发现为 PCa 的治疗提供了新的思路。
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