miR‑203 affects esophageal cancer cell proliferation, apoptosis and invasion by targeting MAP3K1

Zong,Mingzhu; Feng,Wanting; Wan,Li; Yu,Xiaojuan; Yu,Weiyong

doi:10.3892/ol.2020.11610

miR‑203 affects esophageal cancer cell proliferation, apoptosis and invasion by targeting MAP3K1

Authors:
- Mingzhu Zong
- Wanting Feng
- Li Wan
- Xiaojuan Yu
- Weiyong Yu
View Affiliations

Affiliations: Department of Oncology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
Published online on: May 13, 2020 https://doi.org/10.3892/ol.2020.11610
Pages: 751-757
Copyright: © Zong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

miR-203 has been indicated to be a tumor suppressor in esophageal cancer, however, the underlying molecular mechanisms by which it functions are not fully understood. The present study aimed to investigate the molecular mechanisms underlying the regulatory activities of microRNA (miR)‑203 in esophageal cancer. The miR‑203 mimic/inhibitor, Mitogen‑Activated Protein Kinase Kinase Kinase 1 (MAP3K1) overexpression plasmid and MAP3K1 small interfering (si)RNA were transfected into TE‑1 cells. miR‑203 and MAP3K1 mRNA expression were detected via reverse transcription‑quantitative PCR analysis, while MAP3K1 protein expression was detected via western blot analysis. Dual‑luciferase reporter assay was used to determine whether MAP3K1 was a direct target of miR‑203. Cell proliferation and invasion abilities were assessed via MTT and Matrigel assays, respectively. Cell apoptosis was analyzed via flow cytometry, Caspase 8/3 Assay kits and western blot analysis. The results demonstrated that MAP3K1 was a direct target of miR‑203. Overexpression of MAP3K1 reversed the suppressed cell proliferation and invasion abilities induced by miR‑203 mimic, as well as the inhibitory effect of miR‑203 mimic on cell apoptosis. Furthermore, MAP3K1 siRNA weakened the effect of miR‑203 inhibitor on cell proliferation, apoptosis and invasion.

View Figures

View References

1	Global Burden of Disease Cancer Collaboration, . Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, Allen C, Hansen G, Woodbrook R, et al: The global burden of cancer 2013. JAMA Oncol. 1:505–527. 2015. View Article : Google Scholar : PubMed/NCBI
2	Yokota T, Igaki H, Kato K, Tsubosa Y, Mizusawa J, Katayama H, Nakamura K, Fukuda H and Kitagawa Y: Accuracy of preoperative diagnosis of lymph node metastasis for thoracic esophageal cancer patients from JCOG9907 trial. Int J Clin Oncol. 21:283–288. 2016. View Article : Google Scholar : PubMed/NCBI
3	Kamangar F, Dores GM and Anderson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: Defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 24:2137–2150. 2006. View Article : Google Scholar : PubMed/NCBI
4	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar : PubMed/NCBI
5	Mohr AM and Mott JL: Overview of microRNA biology. Semin Liver Dis. 35:3–11. 2015. View Article : Google Scholar : PubMed/NCBI
6	Vienberg S, Geiger J, Madsen S and Dalgaard LT: MicroRNAs in metabolism. Acta Physiol (Oxf). 219:346–361. 2017. View Article : Google Scholar : PubMed/NCBI
7	Reddy KB: MicroRNA (miRNA) in cancer. Cancer Cell Int. 15:382015. View Article : Google Scholar : PubMed/NCBI
8	Iorio MV and Croce CM: MicroRNA dysregulation in cancer: Diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med. 4:143–159. 2012. View Article : Google Scholar : PubMed/NCBI
9	Kiselev FL: MicroRNA and cancer. Mol Biol (Mosk). 48:232–242. 2014.(In Russian). PubMed/NCBI
10	Mei LL, Qiu YT, Zhang B and Shi ZZ: MicroRNAs in esophageal squamous cell carcinoma: Potential biomarkers and therapeutic targets. Cancer Biomark. 19:1–9. 2017. View Article : Google Scholar : PubMed/NCBI
11	Liang Y, Yang W, Zhu Y and Yuan Y: Prognostic role of microRNA-203 in various carcinomas: Evidence from a meta-analysis involving 13 studies. SpringerPlus. 5:15382016. View Article : Google Scholar : PubMed/NCBI
12	Chi Y, Jin Q, Liu X, Xu L, He X, Shen Y, Zhou Q, Zhang J and Jin M: miR-203 inhibits cell proliferation, invasion, and migration of non-small-cell lung cancer by downregulating RGS17. Cancer Sci. 108:2366–2372. 2017. View Article : Google Scholar : PubMed/NCBI
13	Shen J, Zhang J, Xiao M, Yang J and Zhang N: miR-203 suppresses bladder cancer cell growth and targets twist1. Oncol Res. 26:1155–1165. 2018. View Article : Google Scholar : PubMed/NCBI
14	Chen LZ, Ding Z, Zhang Y, He ST and Wang XH: MiR-203 over-expression promotes prostate cancer cell apoptosis and reduces ADM resistance. Eur Rev Med Pharmacol Sci. 22:3734–3741. 2018.PubMed/NCBI
15	Hezova R, Kovarikova A, Srovnal J, Zemanova M, Harustiak T, Ehrmann J, Hajduch M, Svoboda M, Sachlova M and Slaby O: Diagnostic and prognostic potential of miR-21, miR-29c, miR-148 and miR-203 in adenocarcinoma and squamous cell carcinoma of esophagus. Diagn Pathol. 10:422015. View Article : Google Scholar : PubMed/NCBI
16	Zhang F, Yang Z, Cao M, Xu Y, Li J, Chen X, Gao Z, Xin J, Zhou S, Zhou Z, et al: MiR-203 suppresses tumor growth and invasion and down-regulates MiR-21 expression through repressing Ran in esophageal cancer. Cancer Lett. 342:121–129. 2014. View Article : Google Scholar : PubMed/NCBI
17	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
18	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
19	Zhang SY, Gao F, Peng CG, Zheng CJ and Wu MF: Hsa-miR-203 inhibits fracture healing via targeting PBOV1. Eur Rev Med Pharmacol Sci. 22:5797–5803. 2018.PubMed/NCBI
20	Shi K, Qiu X, Zheng W, Yan D and Peng W: MiR-203 regulates keloid fibroblast proliferation, invasion, and extracellular matrix expression by targeting EGR1 and FGF2. Biomed Pharmacother. 108:1282–1288. 2018. View Article : Google Scholar : PubMed/NCBI
21	Pham TT, Angus SP and Johnson GL: MAP3K1: Genomic alterations in cancer and function in promoting cell survival or apoptosis. Genes Cancer. 4:419–426. 2013. View Article : Google Scholar : PubMed/NCBI
22	Hagemann C and Blank JL: The ups and downs of MEK kinase interactions. Cell Signal. 13:863–875. 2001. View Article : Google Scholar : PubMed/NCBI
23	Bonvin C, Guillon A, van Bemmelen MX, Gerwins P, Johnson GL and Widmann C: Role of the amino-terminal domains of MEKKs in the activation of NF kappa B and MAPK pathways and in the regulation of cell proliferation and apoptosis. Cell Signal. 14:123–131. 2002. View Article : Google Scholar : PubMed/NCBI
24	Kyriakis JM and Avruch J: Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 81:807–869. 2001. View Article : Google Scholar : PubMed/NCBI
25	Uhlik MT, Abell AN, Cuevas BD, Nakamura K and Johnson GL: Wiring diagrams of MAPK regulation by MEKK1, 2, and 3. Biochem Cell Biol. 82:658–663. 2004. View Article : Google Scholar : PubMed/NCBI
26	Lange-Carter CA, Pleiman CM, Gardner AM, Blumer KJ and Johnson GL: A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf. Science. 260:315–319. 1993. View Article : Google Scholar : PubMed/NCBI
27	Liu C, Wang S, Zhu S, Wang H, Gu J, Gui Z, Jing J, Hou X and Shao Y: MAP3K1-targeting therapeutic artificial miRNA suppresses the growth and invasion of breast cancer in vivo and in vitro. SpringerPlus. 5:112016. View Article : Google Scholar : PubMed/NCBI
28	Hirano T, Shino Y, Saito T, Komoda F, Okutomi Y, Takeda A, Ishihara T, Yamaguchi T, Saisho H and Shirasawa H: Dominant negative MEKK1 inhibits survival of pancreatic cancer cells. Oncogene. 21:5923–5928. 2002. View Article : Google Scholar : PubMed/NCBI
29	Su F, Li H, Yan C, Jia B, Zhang Y and Chen X: Depleting MEKK1 expression inhibits the ability of invasion and migration of human pancreatic cancer cells. J Cancer Res Clin Oncol. 135:1655–1663. 2009. View Article : Google Scholar : PubMed/NCBI
30	Bian D, Su S, Mahanivong C, Cheng RK, Han Q, Pan ZK, Sun P and Huang S: Lysophosphatidic acid stimulates ovarian cancer cell migration via a ras-MEK kinase 1 pathway. Cancer Res. 64:4209–4217. 2004. View Article : Google Scholar : PubMed/NCBI
31	Zang WQ, Yang X, Wang T, Wang YY, Du YW, Chen XN, Li M and Zhao GQ: MiR-451 inhibits proliferation of esophageal carcinoma cell line EC9706 by targeting CDKN2D and MAP3K1. World J Gastroenterol. 21:5867–5876. 2015. View Article : Google Scholar : PubMed/NCBI