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miR-183-5p 通过靶向 TET1 促进前列腺癌的迁移和侵袭。

MiR-183-5p promotes migration and invasion of prostate cancer by targeting TET1.

机构信息

Clinical Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.

Department of Urology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

BMC Urol. 2023 Jul 10;23(1):116. doi: 10.1186/s12894-023-01286-7.

Abstract

BACKGROUND

Prostate cancer (PCa) is one of the common malignant tumors worldwide. MiR-183-5p has been reported involved in the initiation of human PCa, this study aimed to investigate whether miR-183-5p affects the development of prostate cancer.

METHODS

In this study, we analyzed the expression of miR-183-5p in PCa patients and its correlation with clinicopathological parameters based on TCGA data portal. CCK-8, migration assay and invasion and wound-healing assay were performed to detect proliferation, migration and invasion in PCa cells.

RESULTS

We found the expression of miR-183-5p was significantly increased in PCa tissues, and high expression of miR-183 was positively associated with poor prognosis of PCa patients. Over-expression of miR-183-5p promoted the migration, invasion capacities of PCa cells, whereas knockdown of miR-183-5p showed reversed function. Furthermore, luciferase reporter assay showed TET1 was identified as a direct target of miR-183-5p, which was negatively correlation with miR-183-5p expression level. Importantly, rescue experiments demonstrated TET1 over-expression could reverse miR-183-5p mimic induced-acceleration of PCa malignant progression.

CONCLUSION

Our results indicated that miR-183-5p could act as a tumor promoter in PCa and it accelerated the malignant progression of PCa by directly targeting and down-regulating TET1.

摘要

背景

前列腺癌(PCa)是全球常见的恶性肿瘤之一。有研究报道 miR-183-5p 参与了人类 PCa 的发生,本研究旨在探讨 miR-183-5p 是否影响前列腺癌的发展。

方法

本研究基于 TCGA 数据门户分析了 PCa 患者 miR-183-5p 的表达及其与临床病理参数的相关性。通过 CCK-8 实验、迁移实验、侵袭和划痕愈合实验检测 miR-183-5p 过表达对 PCa 细胞增殖、迁移和侵袭能力的影响。

结果

我们发现 miR-183-5p 在 PCa 组织中的表达显著升高,且高表达与 PCa 患者的不良预后呈正相关。miR-183-5p 的过表达促进了 PCa 细胞的迁移和侵袭能力,而 miR-183-5p 的敲低则显示出相反的功能。此外,荧光素酶报告实验表明 TET1 是 miR-183-5p 的直接靶基因,与 miR-183-5p 的表达水平呈负相关。重要的是,挽救实验表明 TET1 的过表达可以逆转 miR-183-5p 模拟物诱导的 PCa 恶性进展的加速作用。

结论

我们的研究结果表明,miR-183-5p 可以作为 PCa 的肿瘤促进因子,通过直接靶向和下调 TET1 加速 PCa 的恶性进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e71/10334645/ebff85027735/12894_2023_1286_Fig1_HTML.jpg

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