Silencing of long non-coding RNA TUC338 inhibits the malignant phenotype of nasopharyngeal cancer cells via modulating the miR-1226-3p/FGF2 axis

Springer Science and Business Media LLC
Jian Wang1, Liping Li1, Xue Jiang1, Bin Wang1, Xiaodong Hu1, Weiwei Liu1, Ying Zhang2
1Department of Otolaryngology, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061000, Hebei, China
2Infection Department, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061000, Hebei, China

Tóm tắt

AbstractLong noncoding RNAs (lncRNAs) have been suggested as essential regulators in the cancer progression. LncRNA TUC338 was found to promote the malignancy of various cancers, however, the involvement of TUC338 in nasopharyngeal cancer (NPC) has not been well characterized. Here, our results found the significant overexpression of TUC338 in NPC tissues. Higher level of TUC338 was also observed in NPC cells. Interestingly, NPC patients harboring overexpressed TUC338 have worse prognosis. Functional study indicated that down-regulated TUC338 remarkably suppressed the NPC cell proliferation and cell migration. Notably, depletion of TUC338 significantly inhibited the in vivo tumor growth. Mechanistically, TUC338 acted as molecular sponge of miR-1226-3p and attenuated the negative regulation of miR-1226-3p on the expression of fibroblast growth factor 2 (FGF2). Down-regulation of TUC338 inhibited FGF2 expression in NPC cells and tumor tissues. Overexpression of FGF2 attenuated the suppressed NPC proliferation upon the depletion of TUC338. Our results demonstrated the novel function of TUC338/miR-1226-3p/FGF2 axis in NPC progression, suggesting the potential diagnosis and therapeutics significance of TUC338 in NPC.

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Tài liệu tham khảo

Wei WI, Sham JS. Nasopharyngeal carcinoma. Lancet. 2005;365:2041–54. https://doi.org/10.1016/S0140-6736(05)66698-6.

Sun Y, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016;17:1509–20. https://doi.org/10.1016/S1470-2045(16)30410-7.

Huarte M. The emerging role of lncRNAs in cancer. Nat Med. 2015;21:1253–61. https://doi.org/10.1038/nm.3981.

Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155–9. https://doi.org/10.1038/nrg2521.

Schmitt AM, Chang HY. Long noncoding RNAs in cancer pathways. Cancer Cell. 2016;29:452–63. https://doi.org/10.1016/j.ccell.2016.03.010.

Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013;152:1298–307. https://doi.org/10.1016/j.cell.2013.02.012.

St Laurent G, Wahlestedt C, Kapranov P. The landscape of long noncoding RNA classification. Trends Genet. 2015;31:239–51. https://doi.org/10.1016/j.tig.2015.03.007.

Jarroux J, Morillon A, Pinskaya M. History, discovery, and classification of lncRNAs. Adv Exp Med Biol. 2017;1008:1–46. https://doi.org/10.1007/978-981-10-5203-3_1.

Perez DS, et al. Long, abundantly expressed non-coding transcripts are altered in cancer. Hum Mol Genet. 2008;17:642–55. https://doi.org/10.1093/hmg/ddm336.

Iorio MV, Croce CM. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med. 2017;9:852. https://doi.org/10.15252/emmm.201707779.

Kwak PB, Iwasaki S, Tomari Y. The microRNA pathway and cancer. Cancer Sci. 2010;101:2309–15. https://doi.org/10.1111/j.1349-7006.2010.01683.x.

Farazi TA, Spitzer JI, Morozov P, Tuschl T. miRNAs in human cancer. J Pathol. 2011;223:102–15. https://doi.org/10.1002/path.2806.

Mohr AM, Mott JL. Overview of microRNA biology. Semin Liver Dis. 2015;35:3–11. https://doi.org/10.1055/s-0034-1397344.

Fabian MR, Sonenberg N, Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 2010;79:351–79. https://doi.org/10.1146/annurev-biochem-060308-103103.

Qu J, Li M, Zhong W, Hu C. Competing endogenous RNA in cancer: a new pattern of gene expression regulation. Int J Clin Exp Med. 2015;8:17110–6.

Ouyang KX, et al. TUC338 overexpression leads to enhanced proliferation and reduced apoptosis in tongue squamous cell carcinoma cells in vitro. J Oral Maxillofac Surg. 2017;75:423–8. https://doi.org/10.1016/j.joms.2016.08.009.

Jin W, et al. Long non-coding RNA TUC338 is functionally involved in sorafenib-sensitized hepatocarcinoma cells by targeting RASAL1. Oncol Rep. 2017;37:273–80. https://doi.org/10.3892/or.2016.5248.

Li Q, Shen F, Wang C. TUC338 promotes cell migration and invasion by targeting TIMP1 in cervical cancer. Oncol Lett. 2017;13:4526–32. https://doi.org/10.3892/ol.2017.5971.

Zhang YX, Yuan J, Gao ZM, Zhang ZG. LncRNA TUC338 promotes invasion of lung cancer by activating MAPK pathway. Eur Rev Med Pharmacol Sci. 2018;22:443–9. https://doi.org/10.26355/eurrev_201801_14193.

Li G, et al. lncRNA TUC338 is a potential diagnostic biomarker for bladder cancer. J Cell Biochem. 2019;120:18014–9. https://doi.org/10.1002/jcb.29104.

Li G, et al. LncRNA TUC338 is overexpressed in prostate carcinoma and downregulates miR-466. Gene. 2019;707:224–30. https://doi.org/10.1016/j.gene.2019.05.026.

Gospodarowicz D, Jones KL, Sato G. Purification of a growth factor for ovarian cells from bovine pituitary glands. Proc Natl Acad Sci USA. 1974;71:2295–9. https://doi.org/10.1073/pnas.71.6.2295.

Cronauer MV, Schulz WA, Seifert HH, Ackermann R, Burchardt M. Fibroblast growth factors and their receptors in urological cancers: basic research and clinical implications. Eur Urol. 2003;43:309–19. https://doi.org/10.1016/s0302-2838(03)00005-8.

Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010;10:116–29. https://doi.org/10.1038/nrc2780.

Farhat FS, et al. Expression, prognostic and predictive impact of VEGF and bFGF in non-small cell lung cancer. Crit Rev Oncol Hematol. 2012;84:149–60. https://doi.org/10.1016/j.critrevonc.2012.02.012.

He R, et al. The role of long non-coding RNAs in nasopharyngeal carcinoma: as systemic review. Oncotarget. 2017;8:16075–83. https://doi.org/10.18632/oncotarget.14211.

Wu J, Hann SS. Functions and roles of long-non-coding RNAs in human nasopharyngeal carcinoma. Cell Physiol Biochem. 2018;45:1191–204. https://doi.org/10.1159/000487451.

Chen X, et al. miR-1226-3p promotes sorafenib sensitivity of hepatocellular carcinoma via downregulation of DUSP4 expression. J Cancer. 2019;10:2745–53. https://doi.org/10.7150/jca.31804.

Li XY, et al. The long noncoding RNA MIR210HG promotes tumor metastasis by acting as a ceRNA of miR-1226-3p to regulate mucin-1c expression in invasive breast cancer. Aging. 2019;11:5646–65. https://doi.org/10.18632/aging.102149.

Coleman SJ, et al. Nuclear translocation of FGFR1 and FGF2 in pancreatic stellate cells facilitates pancreatic cancer cell invasion. EMBO Mol Med. 2014;6:467–81. https://doi.org/10.1002/emmm.201302698.

Chen Y, et al. FGF2-mediated reciprocal tumor cell-endothelial cell interplay contributes to the growth of chemoresistant cells: a potential mechanism for superficial bladder cancer recurrence. Tumour Biol. 2016;37:4313–21. https://doi.org/10.1007/s13277-015-4214-4.

Giulianelli S, et al. FGF2 induces breast cancer growth through ligand-independent activation and recruitment of ERalpha and PRBDelta4 isoform to MYC regulatory sequences. Int J Cancer. 2019;145:1874–88. https://doi.org/10.1002/ijc.32252.

Li L, et al. FGF2 and FGFR2 in patients with idiopathic pulmonary fibrosis and lung cancer. Oncol Lett. 2018;16:2490–4. https://doi.org/10.3892/ol.2018.8903.

Hu Y, et al. miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer. Cell Death Dis. 2016;7: e2291. https://doi.org/10.1038/cddis.2016.194.

Zhang H, et al. MiR-148b-3p inhibits renal carcinoma cell growth and pro-angiogenic phenotype of endothelial cell potentially by modulating FGF2. Biomed Pharmacother. 2018;107:359–67. https://doi.org/10.1016/j.biopha.2018.07.054.

Chen F, et al. miR-23a-3p suppresses cell proliferation in oral squamous cell carcinomas by targeting FGF2 and correlates with a better prognosis: miR-23a-3p inhibits OSCC growth by targeting FGF2. Pathol Res Pract. 2019;215:660–7. https://doi.org/10.1016/j.prp.2018.12.021.

Huang X, Wang L, Liu W, Li F. MicroRNA-497-5p inhibits proliferation and invasion of non-small cell lung cancer by regulating FGF2. Oncol Lett. 2019;17:3425–31. https://doi.org/10.3892/ol.2019.9954.

Sun Y, Cheng Y, Zhang Y, Han K. MicroRNA-889-3p targets FGFR2 to inhibit cervical cancer cell viability and invasion. Exp Ther Med. 2019;18:1440–8. https://doi.org/10.3892/etm.2019.7675.

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