miR‑4735‑3p inhibits cell migration and invasion of gastric cancer by downregulating NEDD9

Ma,Yanchun

doi:10.3892/ol.2022.13373

miR‑4735‑3p inhibits cell migration and invasion of gastric cancer by downregulating NEDD9

Authors:
- Yanchun Ma
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Affiliations: Department of Gastroenterology, General Hospital of Southern Theater Command, Guangzhou, Guangdong 510010, P.R. China
Published online on: June 10, 2022 https://doi.org/10.3892/ol.2022.13373
Article Number: 253
Copyright: © Ma . This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric cancer (GC) comprises the 3rd cause of cancer‑related death worldwide. Increased expression of neural precursor cell expressed, developmentally downregulated 9 (NEDD9) is commonly observed in GC, however, its underlying molecular mechanism in GC remains unknown. The potential interaction between miR‑4735‑3p and NEDD9 was predicted by TargetScan 7.1. Expression profiles of miR‑4735‑3p and NEDD9 were examined between GC tissues and normal tissues by reverse transcription‑quantitative (RT‑q) PCR. The relationship between miR‑4735‑3p and NEDD9 was validated by RT‑qPCR, western blotting, dual luciferase reporter assay and RNA immunoprecipitation assay. Biological relationship between miR‑4735‑3p and NEDD9 was evidenced by the cell invasion and cell migration assays. NEDD9 level was negatively associated with miR‑4735‑3p level in GC tissues. miR‑4735‑3p suppressed NEDD9 levels in GC cells. NEDD9 was revealed to be a target gene of miR‑4735‑3p. miR‑4735‑3p overexpression suppressed cell migration and invasion of GC cells, which were antagonized by overexpression of NEDD9. Moreover, miR‑4735‑3p mimic decreased the levels of matrix metalloproteinases 2/9, increased the level of E‑cadherin, which were reversed by overexpression of NEDD9. Collectively, the present study provided a potential mechanism for the tumor suppressor role of miR‑4735‑3p in GC by targeting NEDD9.

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1	Bray JA, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
3	Matsuoka T and Yashiro M: Rho/ROCK signaling in motility and metastasis of gastric cancer. World J Gastroenterol. 20:13756–13766. 2014. View Article : Google Scholar : PubMed/NCBI
4	Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, et al: Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: A randomised phase III noninferiority trial. Ann Oncol. 20:666–673. 2009. View Article : Google Scholar : PubMed/NCBI
5	Yuan DD, Zhu ZX, Zhang X and Liu J: Targeted therapy for gastric cancer: Current status and future directions (Review). Oncol Rep. 35:1245–1254. 2016. View Article : Google Scholar : PubMed/NCBI
6	O'Neill GM, Fashena SJ and Golemis EA: Integrin signalling: A new Cas(t) of characters enters the stage. Trends Cell Biol. 10:111–119. 2000. View Article : Google Scholar : PubMed/NCBI
7	Law SF, Estojak J, Wang B, Mysliwiec T, Kruh G and Golemis EA: Human enhancer of filamentation 1, a novel p130cas-like docking protein, associates with focal adhesion kinase and induces pseudohyphal growth in saccharomyces cerevisiae. Mol Cell Biol. 16:3327–3337. 1996. View Article : Google Scholar : PubMed/NCBI
8	Kim M, Gans JD, Nogueira C, Wang A, Paik JH, Feng B, Brennan C, Hahn WC, Cordon-Cardo C, Wagner SN, et al: Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene. Cell. 125:1269–1281. 2006. View Article : Google Scholar : PubMed/NCBI
9	Zhang Q, Wang H, Ma Y, Zhang J, He X, Ma J and Zhao ZS: Overexpression of Nedd9 is a prognostic marker of human gastric cancer. Med Oncol. 31:332014. View Article : Google Scholar : PubMed/NCBI
10	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
11	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
12	Jiang C, Chen X, Alattar M, Wei J and Liu H: MicroRNAs in tumorigenesis, metastasis, diagnosis and prognosis of gastric cancer. Cancer Gene Ther. 22:291–301. 2015. View Article : Google Scholar : PubMed/NCBI
13	Wang L, Shi G, Zhu D, Jin Y and Yang X: miR-5195-3p suppresses cell proliferation and induces apoptosis by directly targeting NEDD9 in osteosarcoma. Cancer Biother Radiopharm. 34:405–412. 2019. View Article : Google Scholar : PubMed/NCBI
14	Lu R, Ji Z, Li X, Zhai Q, Zhao C, Jiang Z, Zhang S, Nie L and Yu Z: miR-145 functions as tumor suppressor and targets two oncogenes, ANGPT2 and NEDD9, in renal cell carcinoma. J Cancer Res Clin Oncol. 140:387–397. 2014. View Article : Google Scholar : PubMed/NCBI
15	Xue Y, Wu T, Sheng Y, Zhong Y, Hu B and Bao C: MicroRNA-1252-5p, regulated by Myb, inhibits invasion and epithelial-mesenchymal transition of pancreatic cancer cells by targeting NEDD9. Aging (Albany NY). 13:18924–18945. 2021. View Article : Google Scholar : PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Shi R, Wang L, Wang T, Xu J, Wang F and Xu M: NEDD9 overexpression correlates with the progression and prognosis in gastric carcinoma. Med Oncol. 31:8522014. View Article : Google Scholar : PubMed/NCBI
18	Zhang S, Wu L, Liu Q, Chen K and Zhang X: Study on effect of the expression of siRNA in gastric cancer bearing nude mice transplanted tumor NEDD9 gene. Pak J Pharm Sci. 27 (5 Suppl):S1651–S1656. 2014.
19	Zhang S, Wu L, Liu Q, Chen K and Zhang X: Impact on growth and invasion of gastric cancer cell lines by silencing NEDD9. Onco Targets Ther. 8:223–231. 2015. View Article : Google Scholar : PubMed/NCBI
20	Zhao S, Min P, Liu L, Zhang L, Zhang Y, Wang Y, Zhao X, Ma Y, Xie H, Zhu C, et al: NEDD9 facilitates hypoxia-induced gastric cancer cell migration via MICAL1 related Rac1 activation. Front Pharmacol. 10:2912019. View Article : Google Scholar : PubMed/NCBI
21	Elaidy NF, Harb OA, Mohamed AM, Hemeda R, Taha HF, Samir A, Elsayed AM, Osman G and Hendawy EIE: Prognostic significances of NEDD-9 and FOXL-1 expression in intestinal type gastric carcinoma: An immunohistochemical study. J Gastrointest Cancer. 52:728–737. 2021. View Article : Google Scholar : PubMed/NCBI
22	Lerotić I, Vuković P, Hrabar D, Misir Z, Kruljac I, Pavić T, Forgač J, Ćaćić P and Ulamec M: Expression of NEDD9 and connexin-43 in neoplastic and stromal cells of gastric adenocarcinoma. Bosn J Basic Med Sci. 21:542–548. 2021.PubMed/NCBI
23	Wang D, Han X, Li C and Bai W: FBXL3 is regulated by miRNA-4735-3p and suppresses cell proliferation and migration in non-small cell lung cancer. Pathol Res Pract. 215:358–365. 2019. View Article : Google Scholar : PubMed/NCBI
24	Zhou W, Huang S, Jiang Q and Yuan T: Suppression of miR-4735-3p in androgen receptor-expressing prostate cancer cells increases cell death during chemotherapy. Am J Transl Res. 9:3714–3722. 2017.PubMed/NCBI
25	Teng J, Ai X, Jia Z, Wang K, Guan Y and Guo Y: Long non-coding RNA ARAP1-AS1 promotes the progression of bladder cancer by regulating miR-4735-3p/NOTCH2 axis. Cancer Biol Ther. 20:552–561. 2019. View Article : Google Scholar : PubMed/NCBI
26	Li C, Dong B, Xu X, Li Y, Wang Y and Li X: LncRNA ARAP1-AS1 aggravates the malignant phenotypes of ovarian cancer cells through sponging miR-4735-3p to enhance PLAGL2 expression. Cytotechnology. 73:363–372. 2021. View Article : Google Scholar : PubMed/NCBI
27	Li L and Li H: Role of microRNA-mediated MMP regulation in the treatment and diagnosis of malignant tumors. Cancer Biol Ther. 14:796–805. 2013. View Article : Google Scholar : PubMed/NCBI
28	Ren F, Tang R, Zhang X, Madushi WM, Luo D, Dang Y, Li Z, Wei K and Chen G: Overexpression of MMP family members functions as prognostic biomarker for breast cancer patients: A systematic review and meta-analysis. PLoS One. 10:e01355442015. View Article : Google Scholar : PubMed/NCBI
29	Fioruci-Fontanelli BA, Chuffa LG, Mendes LO, Pinheiro PF, Delella FK, Kurokawa CS, Felisbino SL and Martinez FE: MMP-2 and MMP-9 activities and TIMP-1 and TIMP-2 expression in the prostatic tissue of two ethanol-preferring rat models. Anal Cell Pathol (Amst). 2015:9545482015.PubMed/NCBI
30	Mareel M, Bracke M, Van Roy F and Vakaet L: Expression of E-cadherin in embryogenetic ingression and cancer invasion. Int J Dev Biol. 37:227–235. 1993.PubMed/NCBI
31	Grauzam S, Brock AM, Holmes CO, Tiedeken JA, Boniface SG, Pierson BN, Patterson DG, Coaxum SD, Neskey DM and Rosenzweig SA: NEDD9 stimulated MMP9 secretion is required for invadopodia formation in oral squamous cell carcinoma. Oncotarget. 9:25503–25516. 2018. View Article : Google Scholar : PubMed/NCBI
32	Meng H, Wu J, Huang Q, Yang X, Yang K, Qiu Y, Ren J, Shen R and Qi H: NEDD9 promotes invasion and migration of colorectal cancer cell line HCT116 via JNK/EMT. Oncol Lett. 18:4022–4029. 2019.PubMed/NCBI