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

Overview

Journal Anal Cell Pathol (Amst)

Specialties Cell Biology
Oncology
Pathology

Date 2022 Jun 1

PMID 35646516

Authors

Cairong Zhu

Zhiquan Song

Zhen Chen

Tianqi Lin

Haili Lin

Zhenqiang Xu

Fen Ai

Shijiao Zheng

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Analysis of immune cell activation in patients with diabetes foot ulcer from the perspective of single cell.

Vu L, Xu F, Li T, Hua Q, Kuang X, Jiang Y Eur J Med Res. 2024; 29(1):606.

PMID: 39702546 PMC: 11657181. DOI: 10.1186/s40001-024-02179-7.

Inhibition of SLC40A1 represses osteoblast formation via inducing iron accumulation and activating the PERK/ATF4/CHOP pathway mediated oxidative stress.

Fang Y, Li W, Dong C, Gao B, Guo W, Li M Redox Rep. 2024; 29(1):2428147.

PMID: 39607819 PMC: 11610352. DOI: 10.1080/13510002.2024.2428147.

Critical role of non-coding RNA-mediated ferroptosis in urologic malignancies.

Li W, Zheng L, Luo P, Chen T, Zou J, Chen Q Front Immunol. 2024; 15:1486229.

PMID: 39544949 PMC: 11560455. DOI: 10.3389/fimmu.2024.1486229.

Mechanisms of ferroptosis and targeted therapeutic approaches in urological malignancies.

Ma W, Jiang X, Jia R, Li Y Cell Death Discov. 2024; 10(1):432.

PMID: 39384767 PMC: 11464522. DOI: 10.1038/s41420-024-02195-w.

The significance of ferroptosis in renal diseases and its therapeutic potential.

Jiang M, Wu S, Xie K, Zhou G, Zhou W, Bao P Heliyon. 2024; 10(16):e35882.

PMID: 39220983 PMC: 11363859. DOI: 10.1016/j.heliyon.2024.e35882.

References

Luis G, Godfroid A, Nishiumi S, Cimino J, Blacher S, Maquoi E . Tumor resistance to ferroptosis driven by Stearoyl-CoA Desaturase-1 (SCD1) in cancer cells and Fatty Acid Biding Protein-4 (FABP4) in tumor microenvironment promote tumor recurrence. Redox Biol. 2021; 43:102006. PMC: 8163990. DOI: 10.1016/j.redox.2021.102006. View

Yang L, Hou Y, Du Y, Li Q, Zhou F, Li Y . Mirtronic miR-4646-5p promotes gastric cancer metastasis by regulating ABHD16A and metabolite lysophosphatidylserines. Cell Death Differ. 2021; 28(9):2708-2727. PMC: 8408170. DOI: 10.1038/s41418-021-00779-y. View

Wang S, Chen S, Ying Y, Ma X, Shen H, Li J . Comprehensive Analysis of Ferroptosis Regulators With Regard to PD-L1 and Immune Infiltration in Clear Cell Renal Cell Carcinoma. Front Cell Dev Biol. 2021; 9:676142. PMC: 8287329. DOI: 10.3389/fcell.2021.676142. View

Zheng Q, Li P, Zhou X, Qiang Y, Fan J, Lin Y . Deficiency of the X-inactivation escaping gene in clear cell renal cell carcinoma promotes tumorigenicity by reprogramming glycogen metabolism and inhibiting ferroptosis. Theranostics. 2021; 11(18):8674-8691. PMC: 8419058. DOI: 10.7150/thno.60233. View

Zhang X, Hu C, Zhang N, Wei W, Li L, Wu H . Matrine attenuates pathological cardiac fibrosis via RPS5/p38 in mice. Acta Pharmacol Sin. 2020; 42(4):573-584. PMC: 8115053. DOI: 10.1038/s41401-020-0473-8. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2020. CA Cancer J Clin. 2020; 70(1):7-30. DOI: 10.3322/caac.21590. View

Oliveira T, Hermann E, Lin D, Chowanadisai W, Hull E, Montgomery M . HDAC inhibition induces EMT and alterations in cellular iron homeostasis to augment ferroptosis sensitivity in SW13 cells. Redox Biol. 2021; 47:102149. PMC: 8487084. DOI: 10.1016/j.redox.2021.102149. View

Wang L, Liu Y, Du T, Yang H, Lei L, Guo M . ATF3 promotes erastin-induced ferroptosis by suppressing system Xc. Cell Death Differ. 2019; 27(2):662-675. PMC: 7206049. DOI: 10.1038/s41418-019-0380-z. View

Woo S, Seo S, Min K, Im S, Nam J, Chang J . Corosolic Acid Induces Non-Apoptotic Cell Death through Generation of Lipid Reactive Oxygen Species Production in Human Renal Carcinoma Caki Cells. Int J Mol Sci. 2018; 19(5). PMC: 5983573. DOI: 10.3390/ijms19051309. View

10.

Yu J, Wang Y, Zhou S, Li J, Wang J, Chi D . Remote loading paclitaxel-doxorubicin prodrug into liposomes for cancer combination therapy. Acta Pharm Sin B. 2020; 10(9):1730-1740. PMC: 7564015. DOI: 10.1016/j.apsb.2020.04.011. View

11.

Hu C, Zhang X, Song P, Yuan Y, Kong C, Wu H . Meteorin-like protein attenuates doxorubicin-induced cardiotoxicity via activating cAMP/PKA/SIRT1 pathway. Redox Biol. 2020; 37:101747. PMC: 7558217. DOI: 10.1016/j.redox.2020.101747. View

12.

Wang J, Yin X, He W, Xue W, Zhang J, Huang Y . SUV39H1 deficiency suppresses clear cell renal cell carcinoma growth by inducing ferroptosis. Acta Pharm Sin B. 2021; 11(2):406-419. PMC: 7893126. DOI: 10.1016/j.apsb.2020.09.015. View

13.

Chen Y, Li S, Zhang Y, Wang M, Li X, Liu S . The lncRNA Malat1 regulates microvascular function after myocardial infarction in mice via miR-26b-5p/Mfn1 axis-mediated mitochondrial dynamics. Redox Biol. 2021; 41:101910. PMC: 7937833. DOI: 10.1016/j.redox.2021.101910. View

14.

Lin T, Yang Y, Ye X, Yao J, Zhou H . Low expression of miR-99b promotes progression of clear cell renal cell carcinoma by up-regulating IGF1R/Akt/mTOR signaling. Int J Clin Exp Pathol. 2021; 13(12):3083-3091. PMC: 7791382. View

15.

Kalantzakos T, Sullivan T, Gloria T, Canes D, Moinzadeh A, Rieger-Christ K . MiRNA-424-5p Suppresses Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma and Attenuates Expression of O-GlcNAc-Transferase. Cancers (Basel). 2021; 13(20). PMC: 8533684. DOI: 10.3390/cancers13205160. View

16.

Bao W, Pang P, Zhou X, Hu F, Xiong W, Chen K . Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer's disease. Cell Death Differ. 2021; 28(5):1548-1562. PMC: 8166828. DOI: 10.1038/s41418-020-00685-9. View

17.

Jang S, Chapa-Dubocq X, Tyurina Y, St Croix C, Kapralov A, Tyurin V . Elucidating the contribution of mitochondrial glutathione to ferroptosis in cardiomyocytes. Redox Biol. 2021; 45:102021. PMC: 8187237. DOI: 10.1016/j.redox.2021.102021. View

18.

Jang H, Shin S, Kim C, Won J, Xu R, Kim D . PLK1/vimentin signaling facilitates immune escape by recruiting Smad2/3 to PD-L1 promoter in metastatic lung adenocarcinoma. Cell Death Differ. 2021; 28(9):2745-2764. PMC: 8408167. DOI: 10.1038/s41418-021-00781-4. View

19.

Hou Y, Zhang Q, Pang W, Hou L, Liang Y, Han X . YTHDC1-mediated augmentation of miR-30d in repressing pancreatic tumorigenesis via attenuation of RUNX1-induced transcriptional activation of Warburg effect. Cell Death Differ. 2021; 28(11):3105-3124. PMC: 8563797. DOI: 10.1038/s41418-021-00804-0. View

20.

Deng G, Wang R, Sun Y, Huang C, Yeh S, You B . Targeting androgen receptor (AR) with antiandrogen Enzalutamide increases prostate cancer cell invasion yet decreases bladder cancer cell invasion via differentially altering the AR/circRNA-ARC1/miR-125b-2-3p or miR-4736/PPARγ/MMP-9 signals. Cell Death Differ. 2021; 28(7):2145-2159. PMC: 8257744. DOI: 10.1038/s41418-021-00743-w. View