| Orginal Article |
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| Effects of miR-324-3p Targeting GPX4 on Ferroptosis in Prostate Cancer Cells |
ZHANG Sai,YE Ji-wei,SHEN Yuan-jing,MU Ke-fei,GUO Xin-wu( ) |
| Nanyang Second General Hospital, Nanyang 473000, China |
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Abstract Objective: To explore the effects of miR-324-3p on prostate cancer (PCa) cell ferroptosis and its underlying mechanism. Methods: qRT-PCR was performed to detect the expression of miR-324-3p and glutathione peroxidase 4 (GPX4) mRNA in PCa tissues, matched adjacent tissues, and cell lines. Western blot was employed to examine the protein level of GPX4 in PCa cell lines and normal prostate epithelial cells. CCK-8 assay was used to evaluate cell proliferation. The levels of glutathione (GSH), lipid oxidation, and reactive oxygen species (ROS) were determined using GSH detection assay kit, lipid peroxidation MDA assay kit and DCFH-DA fluorescent probe assay. Dual-luciferase reporter gene was applied to verify the interaction of miR-324-3p and GPX4. Results: The expression of miR-324-3p in PCa tissues was lower than that in the corresponding paracancerous tissues, and the expression of miR-324-3p was downregulated in PCa cell lines compared with normal prostate epithelial cells. GPX4 was highly-expressed in PCa tissues and cell lines in comparison with the corresponding paracancerous tissues and normal prostate epithelial cells. Dual-luciferase reporter results showed that miR-324-3p was directly targeted to negatively regulate GPX4. Overexpression of miR-324-3p significantly inhibited PCa cell proliferation, reduced GSH production and enhanced the levels of lipid oxidation and ROS; while treatment with the ferroptosis inhibitor Fer-1 or GPX4 reversed the promotion effect of miR-324-3p on ferroptosis in PCa cells. Conclusion: miR-324-3p promoted ferroptosis in PCa cells by targeting negative regulation of GPX4 expression and thus exerted anticancer effects on PCa.
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Received: 09 July 2021
Published: 03 March 2022
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Corresponding Authors:
Xin-wu GUO
E-mail: 564622681@qq.com
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| [1] |
Wu M, Huang Y W, Chen T C, et al. LncRNA MEG3 inhibits the progression of prostate cancer by modulating miR-9-5p/QKI-5 axis. Journal of Cellular and Molecular Medicine, 2019, 23(1):29-38.
doi: 10.1111/jcmm.2019.23.issue-1
|
|
|
| [2] |
Liu T, Chi H Y, Chen J L, et al. Curcumin suppresses proliferation and in vitro invasion of human prostate cancer stem cells by ceRNA effect of miR-145 and lncRNA-ROR. Gene, 2017, 631:29-38.
doi: S0378-1119(17)30645-5
pmid: 28843521
|
|
|
| [3] |
Mou Y H, Wang J, Wu J C, et al. Ferroptosis, a new form of cell death: opportunities and challenges in cancer. Journal of Hematology & Oncology, 2019, 12(1):34.
|
|
|
| [4] |
Imai H, Matsuoka M, Kumagai T, et al. Lipid peroxidation-dependent cell death regulated by GPx4 and ferroptosis. Current Topics in Microbiology and Immunology, 2017, 403:143-170.
|
|
|
| [5] |
Han Y Y, Hu H B, zhou J S. Knockdown of LncRNA SNHG7 inhibited epithelial-mesenchymal transition in prostate cancer though miR-324-3p/WNT2B axis in vitro. Pathology - Research and Practice, 2019, 215(10):152537.
doi: 10.1016/j.prp.2019.152537
|
|
|
| [6] |
Liu Q Y, Jiang X X, Tian H N, et al. Long non-coding RNA OIP5-AS1 plays an oncogenic role in ovarian cancer through targeting miR-324-3p/NFIB axis. European Review for Medical and Pharmacological Sciences, 2020, 24(13):7266-7275.
doi: 21881
pmid: 32706064
|
|
|
| [7] |
Liu C, Li G, Yang N T, et al. miR-324-3p suppresses migration and invasion by targeting WNT2B in nasopharyngeal carcinoma. Cancer Cell International, 2017, 17(1):1-7.
doi: 10.1186/s12935-016-0378-2
|
|
|
| [8] |
Kohaar I, Petrovics G, Srivastava S. A rich array of prostate cancer molecular biomarkers: opportunities and challenges. International Journal of Molecular Sciences, 2019, 20(8):1813.
doi: 10.3390/ijms20081813
|
|
|
| [9] |
Kanwal R, Plaga A R, Liu X Q, et al. MicroRNAs in prostate cancer: Functional role as biomarkers. Cancer Letters, 2017, 407:9-20.
doi: 10.1016/j.canlet.2017.08.011
|
|
|
| [10] |
Jin Y Y, Tong S Q, Tong M. Diagnostic value of circulating miR-324 for prostate cancer. Clinical Laboratory, 2019, 65(4):609-619. DOI: 10.7754/clin.lab.2018.180932.
doi: 10.7754/clin.lab.2018.180932
|
|
|
| [11] |
Gao X J, Wang Y, Zhao H, et al. Plasma miR-324-3p and miR-1285 as diagnostic and prognostic biomarkers for early stage lung squamous cell carcinoma. Oncotarget, 2016, 7(37):59664-59675.
doi: 10.18632/oncotarget.v7i37
|
|
|
| [12] |
Xie N, Fei X Q, Liu S L, et al. LncRNA LOXL1-AS1 promotes invasion and proliferation of non-small-cell lung cancer through targeting miR-324-3p. American Journal of Translational Research, 2019, 11(10):6403-6412.
|
|
|
| [13] |
Fang X, Zhang J, Li C Y, et al. Long non-coding RNA SNHG22 facilitates the malignant phenotypes in triple-negative breast cancer via sponging miR-324-3p and upregulating SUDS3. Cancer Cell International, 2020, 20:252.
doi: 10.1186/s12935-020-01321-9
|
|
|
| [14] |
Zhang N, Zeng X, Sun C N, et al. LncRNA LINC00963 promotes tumorigenesis and radioresistance in breast cancer by sponging miR-324-3p and inducing ACK1 expression. Molecular Therapy Nucleic Acids, 2019, 18:871-881.
doi: 10.1016/j.omtn.2019.09.033
|
|
|
| [15] |
Zhao T C, Zhang J Y, Ye C, et al. lncRNA FOXD2-AS1 promotes hemangioma progression through the miR-324-3p/PDRG1 pathway. Cancer Cell International, 2020, 20:189.
doi: 10.1186/s12935-020-01277-w
|
|
|
| [16] |
Shi Z Z, Fan Z W, Chen Y X, et al. Ferroptosis in carcinoma: regulatory mechanisms and new method for cancer therapy. OncoTargets and Therapy, 2019, 12:11291-11304.
doi: 10.2147/OTT
|
|
|
| [17] |
Xia X J, Fan X P, Zhao M Y, et al. The relationship between ferroptosis and tumors: a novel landscape for therapeutic approach. Current Gene Therapy, 2019, 19(2):117-124.
doi: 10.2174/1566523219666190628152137
|
|
|
| [18] |
Bebber C M, Müller F, Prieto Clemente L, et al. Ferroptosis in cancer cell biology. Cancers, 2020, 12(1):164.
doi: 10.3390/cancers12010164
|
|
|
| [19] |
Tousignant K D, Rockstroh A, Poad B L J, et al. Therapy-induced lipid uptake and remodeling underpin ferroptosis hypersensitivity in prostate cancer. Cancer & Metabolism, 2020, 8:11.
|
|
|
| [20] |
Geybels M S, Hutter C M, Kwon E M, et al. Variation in selenoenzyme genes and prostate cancer risk and survival. Prostate, 2013, 73(7):734-742.
doi: 10.1002/pros.22617
pmid: 23143801
|
|
|
| [21] |
Shen L D, Qi W H, Bai J J, et al. Resibufogenin inhibited colorectal cancer cell growth and tumorigenesis through triggering ferroptosis and ROS production mediated by GPX4 inactivation. Anatomical Record, 2021, 304(2):313-322.
doi: 10.1002/ar.v304.2
|
|
|
| [22] |
Zhao H Y, Ji B, Chen J G, et al. Gpx 4 is involved in the proliferation, migration and apoptosis of glioma cells. Pathology - Research and Practice, 2017, 213(6):626-633.
doi: 10.1016/j.prp.2017.04.025
|
|
|
| [23] |
Zhang X F, Sui S Y, Wang L L, et al. Inhibition of tumor propellant glutathione peroxidase 4 induces ferroptosis in cancer cells and enhances anticancer effect of cisplatin. Journal of Cellular Physiology, 2020, 235(4):3425-3437.
doi: 10.1002/jcp.v235.4
|
|
|
| [24] |
Ye L F, Chaudhary K R, Zandkarimi F, et al. Radiation-induced lipid peroxidation triggers ferroptosis and synergizes with ferroptosis inducers. ACS Chemical Biology, 2020, 15(2):469-484.
doi: 10.1021/acschembio.9b00939
|
|
|
| [25] |
Hou Y F, Cai S, Yu S Y, et al. Metformin induces ferroptosis by targeting miR-324-3p/GPX4 axis in breast cancer. Acta Biochimica et Biophysica Sinica, 2021, 53(3):333-341.
doi: 10.1093/abbs/gmaa180
|
|
|
| [26] |
Deng S H, Wu D M, Li L, et al. miR-324-3p reverses cisplatin resistance by inducing GPX4-mediated ferroptosis in lung adenocarcinoma cell line A549. Biochemical and Biophysical Research Communications, 2021, 549:54-60.
doi: 10.1016/j.bbrc.2021.02.077
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