The mechanism of miR-143-3p regulating FGF-9 in the proliferation, invasion

The study aimed at exploring the miR-143-3p expression and the mechanism involved in ovarian cancer development. RT-qPCR (Quantitative Real-time PCR) served for the detection of the miR-143-3p level in different ovarian carcinoma cells. Then miR-143-3p underwent transfection and presented overexpression in ovarian carcinoma cells. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, flat cloning experiment, Transwell invasion assay and scratch test served for the evaluation of the influences of miR-143-3p on ovarian cancer cell biological behavior. The candidate target genes were screened by using bioinformatics method. The double luciferase assay and Western blot together assessed the regulatory effect of miR-143-3p. Relative to the control group (NC), the overexpressed group presented significantly reduced ovarian cancer cell growth (p < 0.01). The results indicated the inhibitory impact of miR-143-3p overexpression on the invasion and migration of ovarian cancer 3AO and SKOV3 cells. Bioinformatics analysis confirmed FGF-9 (Fibroblast Growth Factor 9) as one of target gene of miR-143-3p. Double luciferase assay also attested the direct negative regulatory impact of miR-143-3p on FGF-9 (p < 0.05). The miR-143-3p overexpression significantly lowered the protein level of FGF-9 in 3AO and SKOV3 cells (p < 0.001). miR-143-3p overexpression negatively regulated the proliferation, invasion and migration abilities of ovarian carcinoma cells, as well as the FGF-9 protein expression.

miR-143-3p; Ovarian carcinoma; Proliferation; Invasion; Migration; FGF-9

[1] Penny SM. Ovarian cancer: an overview. Radiologic Technology. 2020; 91: 561–575.

[2] Wang Y, Meng F, Liu Y, Chen X. Expression of HPIP in epithelial ovarian carcinoma: a clinicopathological study. OncoTargets and Therapy. 2017; 10: 95–100.

[3] Kossaï M, Leary A, Scoazec J, Genestie C. Ovarian cancer: a heterogeneous disease. Pathobiology. 2018; 85: 41–49.

[4] Bogani G, Borghi C, Leone Roberti Maggiore U, Ditto A, Signorelli M, Martinelli F, et al. Minimally invasive surgical staging in early-stage ovarian carcinoma: a systematic review and meta-analysis. Journal of Minimally Invasive Gynecology. 2017; 24: 552–562.

[5] Coughlan AY, Testa G. Exploiting epigenetic dependencies in ovarian cancer therapy. International Journal of Cancer. 2021; 149: 1732–1743.

[6] Zhao L, Guo H, Chen X, Zhang W, He Q, Ding L, et al. Tackling drug resistance in ovarian cancer with epigenetic targeted drugs. European Journal of Pharmacology. 2022; 927: 175071.

[7] Wang Y, Huang Z, Li B, Liu L, Huang C. The emerging roles and therapeutic implications of epigenetic modifications in ovarian cancer. Frontiers in Endocrinology. 2022; 13: 863541.

[8] Záveský L, Jandáková E, Weinberger V, Hanzíková V, Slanař O, Kohoutová M. Ascites in ovarian cancer: MicroRNA deregulations and their potential roles in ovarian carcinogenesis. Cancer Biomarkers. 2022; 33: 1–16.

[9] Chen SN, Chang R, Lin LT, Chen CU, Tsai HW, Wen ZH. MicroRNA in ovarian cancer: biology, pathogenesis, and therapeutic opportunities. International Journal of Environmental Research and Public Health. 2019; 16: 1510.

[10] Ma L, Liang L, Zhou D, Wang S. Tumor suppressor miR-424-5p abrogates ferroptosis in ovarian cancer through targeting ACSL4. Neoplasma. 2021; 68: 165–173.

[11] Vescarelli E, Gerini G, Megiorni F, Anastasiadou E, Pontecorvi P, Solito L, et al. MiR-200c sensitizes Olaparib-resistant ovarian cancer cells by targeting Neuropilin 1. Journal of Experimental & Clinical Cancer Research. 2020; 39: 3.

[12] Cao J, Huo P, Cui K, Wei H, Cao J, Wang J, et al. Follicular fluid-derived exosomal miR-143-3p/miR-155-5p regulate follicular dysplasia by modulating glycolysis in granulosa cells in polycystic ovary syndrome. Cell Communication and Signaling. 2022; 20: 61.

[13] He B, Zhao Z, Cai Q, Zhang Y, Zhang P, Shi S, et al. MiRNA-based biomarkers, therapies, and resistance in cancer. International Journal of Biological Sciences. 2020; 16: 2628–2647.

[14] Wang H, Deng Q, Lv Z, Ling Y, Hou X, Chen Z, et al. N6-methyladenosine induced miR-143-3p promotes the brain metastasis of lung cancer via regulation of VASH1. Molecular Cancer. 2019; 18: 181.

[15] Tang J, Pan H, Wang W, Qi C, Gu C, Shang A, et al. MiR-495-3p and miR-143-3p co-target CDK1 to inhibit the development of cervical cancer. Clinical and Translational Oncology. 2021; 23: 2323–2334.

[16] Zhang J, Huang J, Chen W, Hu Z, Wang X. miR-143-3p Targets lncRNA PSMG3-AS1 to Inhibit the Proliferation of Hepatocellular Carcinoma Cells. Cancer Management and Research. 2020; 12: 6303–6309.

[17] Jiang Z. Molecular mechanism of miR-143-3p regulating lung metastasis of human osteosarcoma (OS) [master’s thesis]. Suzhou University. 2015.

[18] He Z, Yi J, Liu X,Chen J, Han S, Jin L, et al. MiR-143-3p functions as a tumor suppressor by regulating cell proliferation, invasion and epithelial–mesenchymal transition by targeting QKI-5 in esophageal squamous cell carcinoma. Molecular Cancer. 2016; 15: 51.

[19] Schütz LF, Schreiber NB, Gilliam JN, Cortinovis C, Totty ML, Caloni F, et al. Changes in fibroblast growth factor 9 mRNA in granulosa and theca cells during ovarian follicular growth in dairy cattle. Journal of Dairy Science. 2016; 99: 9143–9151.

[20] Totty ML, Morrell BC, Spicer LJ. Fibroblast growth factor 9 (FGF9) regulation of cyclin D1 and cyclin-dependent kinase-4 in ovarian granulosa and theca cells of cattle. Molecular and Cellular Endocrinology. 2017; 440: 25–33.

[21] Zhang YQ, Miao JW. The role of FGF9 in ovarian cancer. Progress in Obstetrics and Gynecology. 2011; 20: 660–662.

[22] Abdel-Rahman WM, Kalinina J, Shoman S, Eissa S, Ollikainen M, Elomaa O, et al. Somatic FGF9 mutations in colorectal and endometrial carcinomas associated with membranous β-cateiiin. Human Mutation. 2008; 29: 390–397.