Lung cancer is an aggressive disease and the leading cause of cancer-related deaths worldwide. In the past several decades, the incidence of adenocarcinoma has significantly increased, and accounts for ~40% of all lung cancer cases. In the present study, we investigated the clinicopathologic significance of microRNA-130b (miR-130b) in lung adenocarcinoma and analyzed its cancer-specific functions. RNA was extracted from formalin-fixed paraffin-embedded specimens of 146 lung adenocarcinoma cases, and miR-130b expression was analyzed using quantitative real-time polymerase chain reaction. NCI-H1650 cells were transfected with miR-130b mimic and inhibitor to determine its effects on tumor cell proliferation, migration, and invasion. The expression of miR-130b in lung adenocarcinoma tissues was classified into two groups according to the median value. High expression of miR-130b was associated with higher histological grade, advanced pathologic T stage, lymph node metastasis, and lymphovascular invasion. Moreover, survival analysis showed that high miR-130b expression was significantly associated with unfavorable prognosis. In addition, miR-130b upregulation promoted cell migration and invasion, while its downregulation resulted in decreased cell proliferation, migration, and wound healing in in vitro experiments. In conclusion, these findings suggest that miR-130b promotes tumor progression and serves as a biomarker of poor prognosis for patients with lung adenocarcinoma. Hence, targeting miR-130b may serve as a potential therapeutic strategy for lung cancer.
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Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.
Duma N, Santana-Davila R, Molina JR. Non-small cell lung cancer: epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc. 2019;94:1623–40.
Arbour KC, Riely GJ. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review. JAMA. 2019;322:764–74.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.
Orellana EA, Kasinski AL. MicroRNAs in cancer: a historical perspective on the path from discovery to therapy. Cancers. 2015;7:1388–405.
Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66.
Kobayashi H, Tomari Y. RISC assembly: coordination between small RNAs and argonaute proteins. Biochim Biophys Acta. 2016;1859:71–81.
Wen D, Danquah M, Chaudhary AK, Mahato RI. Small molecules targeting microRNA for cancer therapy: promises and obstacles. J Control Release. 2015;219:237–47.
Li J, Yang J, Zhou P, Le Y, Zhou C, Wang S, et al. Circular RNAs in cancer: novel insights into origins, properties, functions and implications. Am J Cancer Res. 2015;5:472–80.
Zaravinos A. The regulatory role of microRNAs in EMT and cancer. J Oncol. 2015;2015:865816.
Lan H, Lu H, Wang X, Jin H. MicroRNAs as potential biomarkers in cancer: opportunities and challenges. Biomed Res Int. 2015;2015:125094.
Osaki M, Okada F, Ochiya T. miRNA therapy targeting cancer stem cells: a new paradigm for cancer treatment and prevention of tumor recurrence. Ther Deliv. 2015;6:323–37.
Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.
Di Leva G, Croce CM. miRNA profiling of cancer. Curr Opin Genet Dev. 2013;23:3–11.
Egawa H, Jingushi K, Hirono T, Ueda Y, Kitae K, Nakata W, et al. The miR-130 family promotes cell migration and invasion in bladder cancer through FAK and Akt phosphorylation by regulating PTEN. Sci Rep. 2016;6:20574.
Sheng X, Chen H, Wang H, Ding Z, Xu G, Zhang J, et al. MicroRNA-130b promotes cell migration and invasion by targeting peroxisome proliferator-activated receptor gamma in human glioma. Biomed Pharmacother. 2015;76:121–6.
Yu T, Cao R, Li S, Fu M, Ren L, Chen W, et al. MiR-130b plays an oncogenic role by repressing PTEN expression in esophageal squamous cell carcinoma cells. BMC Cancer. 2015;15:29.
Satterfield L, Shuck R, Kurenbekova L, Allen-Rhoades W, Edwards D, Huang S, et al. miR-130b directly targets ARHGAP1 to drive activation of a metastatic CDC42-PAK1-AP1 positive feedback loop in Ewing sarcoma. Int J Cancer. 2017;141:2062–75.
Tian J, Hu L, Li X, Geng J, Dai M, Bai X. MicroRNA-130b promotes lung cancer progression via PPARgamma/VEGF-A/BCL-2-mediated suppression of apoptosis. J Exp Clin Cancer Res. 2016;35:105.
Li Y, Chen D, Li Y, Jin L, Liu J, Su Z, et al. Identification of miR130b as an oncogene in renal cell carcinoma. Mol Med Rep. 2016;13:1902–8.
Colangelo T, Fucci A, Votino C, Sabatino L, Pancione M, Laudanna C, et al. MicroRNA-130b promotes tumor development and is associated with poor prognosis in colorectal cancer. Neoplasia. 2013;15:1086–99.
Miao Y, Zheng W, Li N, Su Z, Zhao L, Zhou H, et al. MicroRNA-130b targets PTEN to mediate drug resistance and proliferation of breast cancer cells via the PI3K/Akt signaling pathway. Sci Rep. 2017;7:41942.
Zhang Q, Zhang B, Sun L, Yan Q, Zhang Y, Zhang Z, et al. MicroRNA-130b targets PTEN to induce resistance to cisplatin in lung cancer cells by activating Wnt/beta-catenin pathway. Cell Biochem Funct. 2018;36:194–202.
Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. Introduction to the 2015 world health organization classification of tumors of the lung, pleura, thymus, and heart. J Thorac Oncol. 2015;10:1240–2.
Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WE, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11:39–51.
Liu X, Kong C, Zhang Z. miR-130b promotes bladder cancer cell proliferation, migration and invasion by targeting VGLL4. Oncol Rep. 2018;39:2324–32.
Gu JJ, Fan KC, Zhang JH, Chen HJ, Wang SS. Suppression of microRNA-130b inhibits glioma cell proliferation and invasion, and induces apoptosis by PTEN/AKT signaling. Int J Mol Med. 2018;41:284–92.
Gu JJ, Zhang JH, Chen HJ, Wang SS. MicroRNA-130b promotes cell proliferation and invasion by inhibiting peroxisome proliferator-activated receptor-gamma in human glioma cells. Int J Mol Med. 2016;37:1587–93.
Li B, Liu YH, Sun AG, Huan LC, Li HD, Liu DM. MiR-130b functions as a tumor promoter in glioma via regulation of ERK/MAPK pathway. Eur Rev Med Pharmacol Sci. 2017;21:2840–6.
Xiao ZQ, Yin TK, Li YX, Zhang JH, Gu JJ. miR-130b regulates the proliferation, invasion and apoptosis of glioma cells via targeting of CYLD. Oncol Rep. 2017;38:167–74.
Lv M, Zhong Z, Chi H, Huang M, Jiang R, Chen J. Genome-wide screen of miRNAs and targeting mRNAs reveals the negatively regulatory effect of miR-130b-3p on PTEN by PI3K and integrin beta1 signaling pathways in bladder carcinoma. Int J Mol Sci. 2016;18:78.
Hu XY, Li L, Wu HT, Liu Y, Wang BD, Tang Y. Serum miR-130b level, an ideal marker for monitoring the recurrence and prognosis of primary hepatocellular carcinoma after radiofrequency ablation treatment. Pathol Res Pract. 2018;214:1655–60.
Tu K, Zheng X, Dou C, Li C, Yang W, Yao Y, et al. MicroRNA-130b promotes cell aggressiveness by inhibiting peroxisome proliferator-activated receptor gamma in human hepatocellular carcinoma. Int J Mol Sci. 2014;15:20486–99.
Yi R, Li Y, Wang F, Gu J, Isaji T, Li J, et al. Transforming growth factor (TGF) beta1 acted through miR-130b to increase integrin alpha5 to promote migration of colorectal cancer cells. Tumour Biol. 2016;37:10763–73.
Chen H, Yang Y, Wang J, Shen D, Zhao J, Yu Q. miR-130b-5p promotes proliferation, migration and invasion of gastric cancer cells via targeting RASAL1. Oncol Lett. 2018;15:6361–7.
Lai KW, Koh KX, Loh M, Tada K, Subramaniam MM, Lim XY, et al. MicroRNA-130b regulates the tumour suppressor RUNX3 in gastric cancer. Eur J Cancer. 2010;46:1456–63.
Shui Y, Yu X, Duan R, Bao Q, Wu J, Yuan H, et al. miR-130b-3p inhibits cell invasion and migration by targeting the Notch ligand Delta-like 1 in breast carcinoma. Gene. 2017;609:80–87.
Paudel D, Zhou W, Ouyang Y, Dong S, Huang Q, Giri R, et al. MicroRNA-130b functions as a tumor suppressor by regulating RUNX3 in epithelial ovarian cancer. Gene. 2016;586:48–55.
Sun B, Li L, Ma W, Wang S, Huang C. MiR-130b inhibits proliferation and induces apoptosis of gastric cancer cells via CYLD. Tumour Biol. 2016;37:7981–7.
Chen Q, Zhao X, Zhang H, Yuan H, Zhu M, Sun Q, et al. MiR-130b suppresses prostate cancer metastasis through down-regulation of MMP2. Mol Carcinog. 2015;54:1292–1300.
Zhao G, Zhang JG, Shi Y, Qin Q, Liu Y, Wang B, et al. MiR-130b is a prognostic marker and inhibits cell proliferation and invasion in pancreatic cancer through targeting STAT3. PLoS One. 2013;8:e73803.
Wu Y, Sun W, Kong Y, Liu B, Zeng M, Wang W. Restoration of microRNA-130b expression suppresses osteosarcoma cell malignant behavior in vitro. Oncol Lett. 2018;16:97–104.
Yang L, Wang Y, Shi S, Xie L, Liu T, Wang Y, et al. The TNF-alpha-induced expression of miR-130b protects cervical cancer cells from the cytotoxicity of TNF-alpha. FEBS Open Bio. 2018;8:614–27.
Cui X, Kong C, Zhu Y, Zeng Y, Zhang Z, Liu X, et al. miR-130b, an onco-miRNA in bladder cancer, is directly regulated by NF-kappaB and sustains NF-kappaB activation by decreasing Cylindromatosis expression. Oncotarget. 2016;7:48547–61.
Li P, Wang X, Shan Q, Wu Y, Wang Z. MicroRNA-130b promotes cell migration and invasion by inhibiting peroxisome proliferator-activated receptor-gamma in human glioma. Oncol Lett. 2017;13:2615–22.
Wang WY, Zhang HF, Wang L, Ma YP, Gao F, Zhang SJ, et al. High expression of microRNA-130b correlates with poor prognosis of patients with hepatocellular carcinoma. Diagn Pathol. 2014;9:160.
Li C, Feng Y, Coukos G, Zhang L. Therapeutic microRNA strategies in human cancer. AAPS J. 2009;2009:747–757.
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1B07048798). We would like to thank Sungwoong Kim, Jeongyun Eom, and Jisook Kim (Department of Pathology, Hanyang University Hospital) for their technical assistance.
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Kim, Y., Kim, H., Bang, S. et al. MicroRNA-130b functions as an oncogene and is a predictive marker of poor prognosis in lung adenocarcinoma. Lab Invest (2020). https://doi.org/10.1038/s41374-020-00496-z