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miR-383-5p 通过抑制 PI3K/AKT 信号通路在膀胱癌中发挥肿瘤抑制作用。

miR-383-5p serves as a tumor suppressor in bladder cancer by suppressing PI3K/AKT signaling pathway.

机构信息

Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of Urology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China.

出版信息

Cancer Biomark. 2023;37(2):121-131. doi: 10.3233/CBM-220379.

Abstract

BACKGROUND

MicroRNAs have been proven to be key molecules in human malignancy. However, to our knowledge, there is no study reporting miR-383-5p expression level and the role it plays in bladder cancer (BC).

METHODS

We identified miR-383-5p to be one of the tumor-suppressing genes through using data from The Cancer Genome Atlas (TCGA) and GEO database. We evaluate the expression and activity of miR-383-5p in both BC tissue and cell lines. The impacts of miR-383-5p on proliferative, migratory ability and apoptotic rate in BC cell were evaluated by utilizing CCK-8 kits, flow cytometry, and Transwell assays. qRT-PCR, western blot, and luciferase reporter assays have been adopted to investigate the underlying mechanisms. In vivo tumorigenicity testing was conducted to determine the impact of miR-383-5p on BC cellular proliferative capacity.

RESULTS

Reduced miR-383-5p expression has been determined in BC tissue than in normal bladder tissue. Furthermore, BC cell proliferative, migratory ability was inhibited while apoptosis enhanced in vitro and in vivo by miR-383-5p up-regulation. In vitro and in vivo, silencing miR-383-5p considerably improved the growth and invasive capacity of cell, while decreased the apoptotic rates of BC cells.

CONCLUSION

miR-383-5p plays its role as a tumor-suppressing gene by suppressing the PI3K/AKT signaling, hence preventing the development of BC.

摘要

背景

微小 RNA 已被证明是人类恶性肿瘤的关键分子。然而,据我们所知,目前尚无研究报道 miR-383-5p 的表达水平及其在膀胱癌(BC)中的作用。

方法

我们通过使用来自癌症基因组图谱(TCGA)和 GEO 数据库的数据,确定 miR-383-5p 是一种肿瘤抑制基因。我们评估了 miR-383-5p 在 BC 组织和细胞系中的表达和活性。通过 CCK-8 试剂盒、流式细胞术和 Transwell 测定评估 miR-383-5p 对 BC 细胞增殖、迁移能力和凋亡率的影响。采用 qRT-PCR、western blot 和荧光素酶报告基因检测来研究潜在的机制。进行体内肿瘤发生试验以确定 miR-383-5p 对 BC 细胞增殖能力的影响。

结果

与正常膀胱组织相比,BC 组织中 miR-383-5p 的表达降低。此外,通过上调 miR-383-5p,可抑制 BC 细胞的体外和体内增殖、迁移能力,并增强其凋亡。在体外和体内,沉默 miR-383-5p 可显著提高 BC 细胞的生长和侵袭能力,同时降低其凋亡率。

结论

miR-383-5p 通过抑制 PI3K/AKT 信号通路发挥肿瘤抑制基因的作用,从而预防 BC 的发生。

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