MicroRNA-4735-3p Facilitates Ferroptosis in Clear Cell Renal Cell Carcinoma by Targeting SLC40A1

Objective. Clear cell renal cell carcinoma (ccRCC) is the major histopathological subtype of renal cancer, and ferroptosis is implicated in the pathogenesis of ccRCC. The present study was aimed at investigating the role and underlying mechanisms of microRNA-4735-3p (miR-4735-3p) in ccRCC. Methods....

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Main Authors: Cairong Zhu, Zhiquan Song, Zhen Chen, Tianqi Lin, Haili Lin, Zhenqiang Xu, Fen Ai, Shijiao Zheng
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Analytical Cellular Pathology
Online Access:http://dx.doi.org/10.1155/2022/4213401
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author Cairong Zhu
Zhiquan Song
Zhen Chen
Tianqi Lin
Haili Lin
Zhenqiang Xu
Fen Ai
Shijiao Zheng
author_facet Cairong Zhu
Zhiquan Song
Zhen Chen
Tianqi Lin
Haili Lin
Zhenqiang Xu
Fen Ai
Shijiao Zheng
author_sort Cairong Zhu
collection DOAJ
description Objective. Clear cell renal cell carcinoma (ccRCC) is the major histopathological subtype of renal cancer, and ferroptosis is implicated in the pathogenesis of ccRCC. The present study was aimed at investigating the role and underlying mechanisms of microRNA-4735-3p (miR-4735-3p) in ccRCC. Methods. Human ccRCC cell lines were transfected with the miR-4735-3p mimic or inhibitor to manipulate the expression of miR-4735-3p. Cell proliferation, colony formation, cell migration, cell invasion, cell death, oxidative stress, lipid peroxidation, and iron metabolism were determined. To validate the necessity of solute carrier family 40 member 1 (SLC40A1), human ccRCC cell lines were overexpressed with SLC40A1 using adenoviral vectors. Results. miR-4735-3p expression was reduced in human ccRCC tissues and cell lines but elevated upon ferroptotic stimulation. The miR-4735-3p mimic increased, while the miR-4735-3p inhibitor decreased oxidative stress, lipid peroxidation, iron overload, and ferroptosis of human ccRCC cell lines. Mechanistic studies identified SLC40A1 as a direct target of miR-4735-3p, and SLC40A1 overexpression significantly attenuated iron overload and ferroptosis in the miR-4735-3p mimic-treated human ccRCC cell lines. Conclusion. miR-4735-3p facilitates ferroptosis and tumor suppression in ccRCC by targeting SLC40A1.
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spelling doaj-art-07a184a31c314206a980bbed9ef2c12e2025-02-03T06:05:25ZengWileyAnalytical Cellular Pathology2210-71852022-01-01202210.1155/2022/4213401MicroRNA-4735-3p Facilitates Ferroptosis in Clear Cell Renal Cell Carcinoma by Targeting SLC40A1Cairong Zhu0Zhiquan Song1Zhen Chen2Tianqi Lin3Haili Lin4Zhenqiang Xu5Fen Ai6Shijiao Zheng7Hemodialysis RoomDepartment of StomatologyDepartment of EmergencyDepartment of UrologyDepartment of UrologyDepartment of UrologyDepartment of EmergencyHemodialysis RoomObjective. Clear cell renal cell carcinoma (ccRCC) is the major histopathological subtype of renal cancer, and ferroptosis is implicated in the pathogenesis of ccRCC. The present study was aimed at investigating the role and underlying mechanisms of microRNA-4735-3p (miR-4735-3p) in ccRCC. Methods. Human ccRCC cell lines were transfected with the miR-4735-3p mimic or inhibitor to manipulate the expression of miR-4735-3p. Cell proliferation, colony formation, cell migration, cell invasion, cell death, oxidative stress, lipid peroxidation, and iron metabolism were determined. To validate the necessity of solute carrier family 40 member 1 (SLC40A1), human ccRCC cell lines were overexpressed with SLC40A1 using adenoviral vectors. Results. miR-4735-3p expression was reduced in human ccRCC tissues and cell lines but elevated upon ferroptotic stimulation. The miR-4735-3p mimic increased, while the miR-4735-3p inhibitor decreased oxidative stress, lipid peroxidation, iron overload, and ferroptosis of human ccRCC cell lines. Mechanistic studies identified SLC40A1 as a direct target of miR-4735-3p, and SLC40A1 overexpression significantly attenuated iron overload and ferroptosis in the miR-4735-3p mimic-treated human ccRCC cell lines. Conclusion. miR-4735-3p facilitates ferroptosis and tumor suppression in ccRCC by targeting SLC40A1.http://dx.doi.org/10.1155/2022/4213401
spellingShingle Cairong Zhu
Zhiquan Song
Zhen Chen
Tianqi Lin
Haili Lin
Zhenqiang Xu
Fen Ai
Shijiao Zheng
MicroRNA-4735-3p Facilitates Ferroptosis in Clear Cell Renal Cell Carcinoma by Targeting SLC40A1
Analytical Cellular Pathology
title MicroRNA-4735-3p Facilitates Ferroptosis in Clear Cell Renal Cell Carcinoma by Targeting SLC40A1
title_full MicroRNA-4735-3p Facilitates Ferroptosis in Clear Cell Renal Cell Carcinoma by Targeting SLC40A1
title_fullStr MicroRNA-4735-3p Facilitates Ferroptosis in Clear Cell Renal Cell Carcinoma by Targeting SLC40A1
title_full_unstemmed MicroRNA-4735-3p Facilitates Ferroptosis in Clear Cell Renal Cell Carcinoma by Targeting SLC40A1
title_short MicroRNA-4735-3p Facilitates Ferroptosis in Clear Cell Renal Cell Carcinoma by Targeting SLC40A1
title_sort microrna 4735 3p facilitates ferroptosis in clear cell renal cell carcinoma by targeting slc40a1
url http://dx.doi.org/10.1155/2022/4213401
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