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SH3BP5-AS1/IGF2BP2/VDAC2轴促进膀胱癌细胞的凋亡和铁死亡

SH3BP5-AS1/IGF2BP2/VDAC2 Axis Promotes the Apoptosis and Ferroptosis of Bladder Cancer Cells.

作者信息

Shao Yong, Chan Yunhui, Zhao Rong

机构信息

Department of Urology Third Ward, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

出版信息

Bladder Cancer. 2023 Mar 31;9(1):29-40. doi: 10.3233/BLC-211629. eCollection 2023.

DOI:10.3233/BLC-211629
PMID:38994477
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11181683/
Abstract

BACKGROUND

Bladder cancer (BC) is the most common malignant tumor in the urinary system with a high incidence, imposing a burden on the healthcare system worldwide. The participation of long non-coding RNAs (lncRNAs) in BC has attracted increasing attention.

OBJECTIVE

The aim in the current study was to explore the potential mechanism involving SH3BP5-AS1 in modulating BC cell proliferation, apoptosis and ferroptosis.

METHODS

qPCR and WB analysis measured the expression of RNAs and proteins. Functional and mechanism experiments were performed to investigate RNA impacts on cell proliferation, apoptosis and ferroptosis, and explore the correlation between RNA and protein expression.

RESULTS

SH3BP5-AS1 was down-regulated in BC cells, and SH3BP5-AS1 overexpression could inhibit BC cell proliferation but facilitate the cell apoptosis. SH3BP5-AS1 was also found to facilitate the ferroptosis of BC cells. Additionally, SH3BP5-AS1 was confirmed to recruit IGF2BP2 to regulate VDAC2 expression in the mA-dependent manner. VDAC2 was detected to be down-regulated in BC cells and was verified to inhibit BC cell growth. Moreover, it was indicated from rescue assays that SH3BP5-AS1 could modulate VDAC2 expression to promote the ferroptosis of BC cells.

CONCLUSION

SH3BP5-AS1 could affect BC cell proliferation, apoptosis and ferroptosis via IGF2BP2/VDAC2, providing a novel molecular perspective for understanding BC.

摘要

背景

膀胱癌（BC）是泌尿系统中最常见的恶性肿瘤，发病率高，给全球医疗保健系统带来负担。长链非编码RNA（lncRNAs）在膀胱癌中的作用日益受到关注。

目的

本研究旨在探讨SH3BP5-AS1调控膀胱癌细胞增殖、凋亡和铁死亡的潜在机制。

方法

采用qPCR和WB分析检测RNA和蛋白质的表达。进行功能和机制实验，研究RNA对细胞增殖、凋亡和铁死亡的影响，并探讨RNA与蛋白质表达之间的相关性。

结果

SH3BP5-AS1在膀胱癌细胞中表达下调，过表达SH3BP5-AS1可抑制膀胱癌细胞增殖，但促进细胞凋亡。还发现SH3BP5-AS1可促进膀胱癌细胞的铁死亡。此外，证实SH3BP5-AS1以mA依赖的方式招募IGF2BP2来调节VDAC2的表达。检测发现VDAC2在膀胱癌细胞中表达下调，并证实其可抑制膀胱癌细胞生长。此外，挽救实验表明，SH3BP5-AS1可通过调节VDAC2的表达促进膀胱癌细胞的铁死亡。

结论

SH3BP5-AS1可通过IGF2BP2/VDAC2影响膀胱癌细胞的增殖、凋亡和铁死亡，为理解膀胱癌提供了新的分子视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0583/11181683/5c19368e008e/blc-9-blc211629-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0583/11181683/92eab9cbe9e4/blc-9-blc211629-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0583/11181683/ed2ddff0c121/blc-9-blc211629-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0583/11181683/10c154811ea6/blc-9-blc211629-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0583/11181683/7596215b38f4/blc-9-blc211629-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0583/11181683/0f59f7805977/blc-9-blc211629-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0583/11181683/5c19368e008e/blc-9-blc211629-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0583/11181683/92eab9cbe9e4/blc-9-blc211629-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0583/11181683/ed2ddff0c121/blc-9-blc211629-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0583/11181683/10c154811ea6/blc-9-blc211629-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0583/11181683/7596215b38f4/blc-9-blc211629-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0583/11181683/0f59f7805977/blc-9-blc211629-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0583/11181683/5c19368e008e/blc-9-blc211629-g006.jpg

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