Objective To investigate the function and mechanism of miR-330-3p/SLC7A11 in the regulation of proliferation, apoptosis and ferroptosis in oral squamous cell carcinoma by interferon-γ. Methods Human OSCC cell lines were cultured and divided into control group and IFN-γgroup. Cell viability, migration, invasion, and apoptosis were measured by CCK8, colony formation assay, cell invasion assay, and flow cytometry. The expression of miR-330-3p and SLC7A11 in OSCC cells was measured by qPCR and Western blotting. The target sites of miR-330-3p were predicted by TargetScan and confirmed by dual luciferase reporting assay, which manipulated the expression levels of miR-330-3p and SLC7A11 in OSCC cell lines. Ferroptosis and IFN-γ regulation of OSCC cell growth in vivo were detected by iron and ROS level analysis and nude mouse study. Results Compared with the control group, IFN-γsignificantly reduced OSCC cell viability and inhibited the proliferation, migration and invasion of OSCC cells. IFN-γinhibited levels of negative regulators of iron apoptosis in OSCC cells, including GPX4 and SLC7A11, IFN-γ-induced ROS, and accumulation of iron and Fe2+ in OSCC cells. The targeting relationship was verified by luciferase reporting method, and miR-330-3p effectively inhibited SLC7A11 levels in OSCC cells. MiR-330-3p mimics increased OSCC cell migration and decreased apoptosis and ferroptosis. Tumogenicity in nude mice showed that IFN-γinhibited OSCC cell growth in vivo. Conclusion MiR-300-3p inhibits the expression of SLC7A11 to promote IFN-γ-induced proliferation and invasion of OSCC cells, and inhibit cell apoptosis and ferroptosis.
Key words
miR-300-3p /
SLC7A11 /
IFN-γ /
oral squamous cell carcinoma /
ferroptosis
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References
[1] PANARESE I, AQUINO G, RONCHI A, et al.Oral and Oropharyngeal Squamous Cell Carcinoma: Prognostic and Predictive Parameters in the Etiopathogenetic Route[J]. Expert Rev Anticancer Ther, 2019, 19: 105-119.
[2] LI J, CAO F, YIN HL, et al.Ferroptosis: Past, Present and Future[J]. Cell Death Dis, 2020, 11: 88.
[3] INUI M, MARTELLO G, PICCOLO S.MicroRNA control of signal transduction[J]. Nat Rev Mol Cell Biol, 2010, 11(4): 252-263.
[4] SUN D, LI X, MA M, et al.The predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in operable and advanced non-small-cell lung cancer[J]. Jpn J Clin Oncol, 2015, 45(5): 464-473.
[5] YAN LX, HUANG XF, SHAO Q, et al.MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis[J]. RNA, 2008, 14(11): 2348-2360.
[6] LIU MK, MA T, YU Y, et al.MiR-1/GOLPH3/Foxo1 Signaling Pathway Regulates Proliferation of Bladder Cancer[J]. Technol Cancer Res Treat, 2019, 18: 1533033819886897.
[7] LIN W, WANG C, LIU G, et al.SLC7A11/xCT in cancer: biological functions and therapeutic implications[J]. Am J Cancer Res, 2020, 10(10): 3106-3126.
[8] ZHANG P, WANG W, WEI Z, et al.xCT expression modulates cisplatin resistance in Tca8113 tongue carcinoma cells[J]. Oncol Lett, 2016, 12(1): 307-314.
[9] GAO AH, HU YR, ZHU WP.IFN-γ inhibits ovarian cancer progression via SOCS1/JAK/STAT signaling pathway[J]. Clin Transl Oncol, 2022, 24(1): 57-65.
[10] YONEKURA N, YOKOSAWA N, HARIYA Y, et al.Interferon-alpha and interferon-gamma augment apoptosis in oral carcinoma cells treated with Shiga toxin 2(Stx2)[J]. Tumor Res, 2002, 35: 25-33.
[11] CHEN, D, YAN W, LIU Z, et al.Downregulation of miR‐221 enhances the sensitivity of human oral squamous cell carcinoma cells to Adriamycin through upregulation of TIMp3 expression[J]. Biomed Pharmacother, 2016, 77: 72-78.
[12] ZENG Z, VEITCH M, KELLY GA, et al.IFN-γ Critically Enables the Intratumoural Infiltration of CXCR3+ CD8+ T Cells to Drive Squamous Cell Carcinoma Regression[J]. Cancers (Basel), 2021, 13(9): 2131.
[13] ZHOU Z H, ZHAO T C, LIANG S Y, et al.A therapeutic approach with combination of interferon-gamma and autophagy inhibitor for oral squamous cell carcinoma[J]. Am J Cancer Res, 2021, 11(4): 1503-1521.
[14] WEI TT, ZHANG MY, ZHENG XH, et al.Interferon-γ induces retinal pigment epithelial cell Ferroptosis by a JAK1-2/STAT1/SLC7A11 signaling pathway in Age-related Macular Degeneration[J]. FEBS J, 2022, 289(7): 1968-1983.
[15] LI Q, WANG W, ZHANG M, et al.Circular RNA circ-0016068 promotes the growth, migration, and invasion of prostate cancer cells by regulating the miR-330-3p/BMI-1 axis as a competing endogenous RNA[J]. Front Cell Dev Biol, 2020, 8: 827.
[16] CHENG Y, ZHU H, GAO W.MicroRNA-330-3p represses the proliferation and invasion of laryngeal squamous cell carcinoma through downregulation of Tra2β-mediated Akt signaling[J]. Mol Cell Probes, 2020, 52: 101574.
[17] QIAN C, CHEN S, LI S, et al.Circ_0000003 regulates glutamine metabolism and tumor progression of tongue squamous cell carcinoma via the miR-330-3p/GLS axis[J]. Oncol Rep, 2021, 45(4): 45.
[18] MUKHOPADHYAY S, BIANCUR DE, PARKER SJ, et al.Autophagy is Required for Proper Cysteine Homeostasis in Pancreatic Cancer Through Regulation of SLC7A11[J]. Proc Natl Acad Sci USA, 2021, 118(6): e2021475118.
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