MiR-96 induced non-small-cell lung cancer progression through competing endogenous RNA network and affecting EGFR signaling pathway

Document Type : Original Article

Authors

1 Division of Respiratory Disease, Affiliated People’s Hospital of Jiangsu University, Dianli Road No.8, Zhenjiang, 212002, China

2 Division of Nephrology, Affiliated People’s Hospital of Jiangsu University, Dianli Road No.8, Zhenjiang, 212002, China

Abstract

Objective(s): Non-small cell lung cancer (NSCLC) has become a serious global health problem in the 21st century, and tumor proliferation and metastasis are the leading causes of death in patients  with lung cancer. The present study aimed to verify the function of miR-96 and miR-96 in relation to competing with endogenous RNA regulatory network in NSCLC progression including proliferation and metastasis.
Materials and Methods: Clinical data of miR-96 expression was collected from StarBase 2.0 developed by Sun Yat-sen University. We used wound-healing, transwell and MTT assays to measure migration, invasion and proliferation of NSCLC cell lines after different treatment. Quantitative real time PCR and western blot were used to test differential genes expression. In order to identify target between genes (FOXO1 and DUSP1) and miR-96, luciferase assay was used. Luciferase activities in FOXO1 and DUSP1 wild type plasmid groups were compared to mutant groups.
Results: qRT-PCR and online database results indicated that miR-96 is highly associated with NSCLC when compared to normal patients. In addition, miR-96 indeed induced migration, invasion and proliferation of NSCLC cell line. In addition, FOXO1 and DUSP1 are targets of miR-96 and these three molecules form competing endogenous RNA network. miR-96 related competing endogenous RNA network affects cell metastasis via epidermal growth factor receptor (EGFR) signaling.
Conclusion: miR-96 can be considered as one of tumor-inducer and form competing endogenous RNA network with FOXO1 and DUSP1, which affects downstream EGFR signaling.

Keywords

Main Subjects

References

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61:69-90.
2. Nishijima-Futami Y, Minami S, Futami S, Koba T, Higashiguchi M, Tamiya M, et al. Phase II study of S-1 plus bevacizumab combination therapy for patients previously treated for non-squamous non-small cell lung cancer. Cancer Chemothe Pharmacol 2017; 79:1215-1220.
3. Zhu B, Yang J, Zhang P, Shen L, Li X, Li J. Safety and effectiveness of localized lung resection combined with neoadjuvant chemotherapy in the treatment of stage I-II non-small cell lung cancer. Oncol Lett 2017; 13:2344-2348.
4. Dong Y, Jin X, Sun Z, Zhao Y, Song X. MiR-186 inhibited migration of NSCLC via targeting cdc42 and effecting EMT process. Mol Cell 2017; 40:195-201.
5. Liu X, Wang P, Zhang C, Ma Z. Epidermal growth factor receptor (EGFR): a rising star in the era of precision medicine of lung cancer. Oncotarget 2017; 8:50209-50220.
6. Bak RO, Mikkelsen JG. MiRNA sponges: soaking up miRNAs for regulation of gene expression. Wiley Interdiscip Rev RNA 2014; 5:317-333.
7. Chakraborty C, Chin KY, Das S. MiRNA-regulated cancer stem cells: understanding the property and the role of miRNA in carcinogenesis. Tumour Biol 2016; 37:13039-13048.
8. Humphries B, Wang Z, Yang C. The role of microRNAs in metal carcinogen-induced cell malignant transformation and tumorigenesis. Food Chem Toxicol 2016; 98:58-65.
9. Dudics S, Venkatesha SH, Moudgil KD. The micro-RNA expression profiles of autoimmune arthritis reveal novel biomarkers of the disease and therapeutic response. Int J Mol Sci 2018;19:2293-2314.
10. Fei X, Zhang J, Zhao Y, Sun M, Zhao H, Li S. MiR-96 promotes invasion and metastasis by targeting GPC3 in non-small cell lung cancer cells. Oncol Lett 2018; 15:9081-9086.
11. Wang Z, Yang B, Zhang M, Guo W, Wu Z, Wang Y, et al. lncRNA epigenetic landscape analysis identifies EPIC1 as an oncogenic incRNA that interacts with MYC and promotes cell-cycle progression in cancer. Cancer Cell 2018; 33:706-720.
12. He C, Zhang Q, Gu R, Lou Y, Liu W. MiR-96 regulates migration and invasion of bladder cancer through epithelial-mesenchymal transition in response to transforming growth factor-beta1. J Cell Biochem 2018; 119:7807-7817.
13. Zhang L, Quan H, Wang S, Li X, Che X. MiR-183 promotes growth of non-small cell lung cancer cells through FoxO1 inhibition. Tumour Biol 2015; 36:8121-8126.
14. Hou L, Chen J, Zheng Y, Wu C. Critical role of miR-155/FoxO1/ROS axis in the regulation of non-small cell lung carcinomas. Tumour Biol 2016; 37:5185-5192.
15. Chen X, Zhu L, Ma Z, Sun G, Luo X, Li M, et al. Oncogenic miR-9 is a target of erlotinib in NSCLCs. Sci Rep 2015; 5:17031-17042.
16. Zhang K, Wang YW, Wang YY, Song Y, Zhu J, Si PC, et al. Identification of microRNA biomarkers in the blood of breast cancer patients based on microRNA profiling. Gene 2017; 619:10-20.
17. Hong Y, Liang H, Uzair Ur R, Wang Y, Zhang W, Zhou Y, et al. MiR-96 promotes cell proliferation, migration and invasion by targeting PTPN9 in breast cancer. Sci Rep 2016; 6:37421-37437.
18. Budzinska M, Owczarz M, Pawlik-Pachucka E, Roszkowska-Gancarz M, Slusarczyk P, Puzianowska-Kuznicka M. MiR-96, miR-145 and miR-9 expression increases, and IGF-1R and FOXO1 expression decreases in peripheral blood mononuclear cells of aging humans. BMC Geriatr 2016; 16:200-209.
19. Thomson DW, Dinger ME. Endogenous microRNA sponges: evidence and controversy. Nature Rev Genet 2016; 17:272-283.
20. Shen J, Zhang Y, Yu H, Shen B, Liang Y, Jin R, et al. Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy. Cancer Med 2016; 5:2061-2068.
21. Shen J, Zhou S, Shi L, Liu X, Lin H, Yu H, et al. DUSP1 inhibits cell proliferation, metastasis and invasion and angiogenesis in gallbladder cancer. Oncotarget 2017; 8:12133-12144.
22. Delaney C, Frank S, Huang RS. Pharmacogenomics of EGFR-targeted therapies in non-small cell lung cancer: EGFR and beyond. Chin J Cancer 2015; 34:149-160.
23. Huang L, Fu L. Mechanisms of resistance to EGFR tyrosine kinase inhibitors. Acta Pharm Sin B 2015; 5:390-401.
24. Yang J, Li T, Gao C, Lv X, Liu K, Song H, et al. FOXO1 3’UTR functions as a ceRNA in repressing the metastases of breast cancer cells via regulating miRNA activity. FEBS Lett 2014; 588:3218-3224.
25. Zuo C, Li X, Huang J, Chen D, Ji K, Yang Y, et al. Osteoglycin attenuates cardiac fibrosis by suppressing cardiac myofibroblast proliferation and migration throughAntagonizing LPA3/MMP2/EGFR signaling. Cardiovasc Res. 2018; 114:703-712.
26. Du WW, Fang L, Li M, Yang X, Liang Y, Peng C, et al. MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling. J Cell Sci 2013; 126:1440-1453.
27. Tortora G, Bianco R, Daniele G, Ciardiello F, McCubrey JA, Ricciardi MR, et al. Overcoming resistance to molecularly targeted anticancer therapies: rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies. Drug Resist Updat 2007; 10:81-100.
28. Mandel A, Larsson P, Sarwar M, Semenas J, Syed Khaja AS, Persson JL. The interplay between AR, EGF receptor and MMP-9 signaling pathways in invasive prostate cancer. Mol Med 2018; 24:34-47.
29. Majumder A, Ray S, Banerji A. Epidermal growth factor receptor-mediated regulation of matrix metalloproteinase-2 and matrix metalloproteinase-9 in MCF-7 breast cancer cells. Mol Cell Biochem 2018; 452:111-121.
Iranian Journal of Basic Medical Sciences
Volume 22, Issue 8
August 2019
Pages 908-914

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