MicroRNA-145-5p modulates Krüppel-like factor 5 and inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma

BMC Molecular and Cell Biology - 2022
Chien-Han Yuan1, Wei‐Chi Hsu2, A‐Mei Huang3, Ben-Chih Yuan4, I-Hung Chen5, Chia-An Hsu1, Rong-Feng Chen6, Yih-Min Chu1, Hui‐Hui Lin7, Hung‐Lung Ke3
1Department of Otolaryngology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
2Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
4Department of Otolaryngology, Fooyin University Hospital, Pingtung, Taiwan
5Department of Internal Medicine, Pingtung Branch, Kaohsiung Armed Forces General Hospital, Pingtung, Taiwan
6Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan
7Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

Tóm tắt

Abstract Background In several human cancers, Krüppel-like factor 5 (KLF5), a zinc finger transcription factor, can contribute to both tumor progression or suppression; however, the precise role of KLF5 in nasopharyngeal carcinoma (NPC) remains poorly understood. In this study, the association between KLF5 and microRNA-145-5p (miR-145-5p) in NPC cells was elucidated. Results Our results showed that KLF5 expression was up-regulated in NPC group compared to normal group. We found that KLF5 exhibited an oncogenic role in NPC cells. The upregulation of miR-145-5p inhibited the proliferation, migration, and invasion of NPC cells. It was observed that miR-145-5p could down-regulate the mRNA and protein expression of KLF5 in NPC cell lines. Additionally, the activity of focal adhesion kinase (FAK), a migration marker, was regulated by miR-145-5p and KLF5 in NPC cells. Conclusions The results of this study indicated that miR-145-5p could repress the proliferation, migration, and invasion of NPC cells via KLF5/FAK regulation, and could be a potential therapeutic target for patients with NPC.

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Tài liệu tham khảo

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(6):394–424.

Sham JS, Choy D, Wei WI. Nasopharyngeal carcinoma: orderly neck node spread. Int J Radiat Oncol Biol Phys. 1990;19(4):929–33.

Kim YS, Kim BS, Jung SL, Lee YS, Kim MS, Sun DI, et al. Radiation therapy combined with (or without) cisplatin-based chemotherapy for patients with nasopharyngeal cancer: 15-years experience of a single institution in Korea. Cancer Res Treat. 2008;40(4):155–63.

Le QT, Colevas AD, O’Sullivan B, Lee AWM, Lee N, Ma B, et al. Current treatment landscape of nasopharyngeal carcinoma and potential trials evaluating the value of immunotherapy. J Natl Cancer Inst. 2019;111(7):655–63.

Dang DT, Pevsner J, Yang VW. The biology of the mammalian Kruppel-like family of transcription factors. Int J Biochem Cell Biol. 2000;32(11–12):1103–21.

Luo Y, Chen C. The roles and regulation of the KLF5 transcription factor in cancers. Cancer Sci. 2021;112(6):2097–117.

Li Y, Kong R, Chen H, Zhao Z, Li L, Li J, et al. Overexpression of KLF5 is associated with poor survival and G1/S progression in pancreatic cancer. Aging (Albany NY). 2019;11(14):5035–57.

Takagi Y, Sakai N, Yoshitomi H, Furukawa K, Takayashiki T, Kuboki S, et al. High expression of Kruppel-like factor 5 is associated with poor prognosis in patients with colorectal cancer. Cancer Sci. 2020;111(6):2078–92.

Tong D, Czerwenka K, Heinze G, Ryffel M, Schuster E, Witt A, et al. Expression of KLF5 is a prognostic factor for disease-free survival and overall survival in patients with breast cancer. Clin Cancer Res. 2006;12(8):2442–8.

Ma D, Chang LY, Zhao S, Zhao JJ, Xiong YJ, Cao FY, et al. KLF5 promotes cervical cancer proliferation, migration and invasion in a manner partly dependent on TNFRSF11a expression. Sci Rep. 2017;7(1):15683.

Fang W, Li X, Jiang Q, Liu Z, Yang H, Wang S, et al. Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China. J Transl Med. 2008;6:32.

Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33.

Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8.

Lee KT, Tan JK, Lam AK, Gan SY. MicroRNAs serving as potential biomarkers and therapeutic targets in nasopharyngeal carcinoma: a critical review. Crit Rev Oncol Hematol. 2016;103:1–9.

Zhang Z, Luo G, Yu C, Yu G, Jiang R, Shi X. MicroRNA-493-5p inhibits proliferation and metastasis of osteosarcoma cells by targeting Kruppel-like factor 5. J Cell Physiol. 2019;234(8):13525–33.

Liu JY, Lu JB, Xu Y. MicroRNA-153 inhibits the proliferation and invasion of human laryngeal squamous cell carcinoma by targeting KLF5. Exp Ther Med. 2016;11(6):2503–8.

Morimoto Y, Mizushima T, Wu X, Okuzaki D, Yokoyama Y, Inoue A, et al. miR-4711-5p regulates cancer stemness and cell cycle progression via KLF5, MDM2 and TFDP1 in colon cancer cells. Br J Cancer. 2020;122(7):1037–49.

Cui SY, Wang R, Chen LB. MicroRNA-145: a potent tumour suppressor that regulates multiple cellular pathways. J Cell Mol Med. 2014;18(10):1913–26.

Han Q, Wu W, Cui Y. LINC00337 regulates KLF5 and maintains stem-cell like traits of cervical cancer cells by modulating miR-145. Front Oncol. 2020;10:1433.

Liang H, Sun H, Yang J, Yi C. miR1455p reduces proliferation and migration of hepatocellular carcinoma by targeting KLF5. Mol Med Rep. 2018;17(6):8332–8.

Zhou T, Chen S, Mao X. miR-145-5p affects the differentiation of gastric cancer by targeting KLF5 directly. J Cell Physiol. 2019;234(5):7634–44.

Liu SC, Hsu T, Chang YS, Chung AK, Jiang SS, OuYang CN, et al. Cytoplasmic LIF reprograms invasive mode to enhance NPC dissemination through modulating YAP1-FAK/PXN signaling. Nat Commun. 2018;9(1):5105.

Zong D, Jiang N, Xu JH, Wang DJ, Zhu HF, Wu LR, et al. ZNF488 is an independent prognostic indicator in nasopharyngeal carcinoma and promotes cell adhesion and proliferation via collagen IV/FAK/AKT/Cyclin D1 pathway. Cancer Manag Res. 2019;11:5871–82.

Ruiz de Sabando A, Wang C, He Y, Garcia-Barros M, Kim J, Shroyer KR, et al. ML264, A novel small-molecule compound that potently inhibits growth of colorectal cancer. Mol Cancer Ther. 2016;15(1):72–83.

Huang H, Han Y, Chen Z, Pan X, Yuan P, Zhao X, et al. ML264 inhibits osteosarcoma growth and metastasis via inhibition of JAK2/STAT3 and WNT/beta-catenin signalling pathways. J Cell Mol Med. 2020;24(10):5652–64.

Diakiw SM, D’Andrea RJ, Brown AL. The double life of KLF5: opposing roles in regulation of gene-expression, cellular function, and transformation. IUBMB Life. 2013;65(12):999–1011.

Gao Y, Ding Y, Chen H, Chen H, Zhou J. Targeting Kruppel-like factor 5 (KLF5) for cancer therapy. Curr Top Med Chem. 2015;15(8):699–713.

Ma JB, Bai JY, Zhang HB, Jia J, Shi Q, Yang C, et al. KLF5 inhibits STAT3 activity and tumor metastasis in prostate cancer by suppressing IGF1 transcription cooperatively with HDAC1. Cell Death Dis. 2020;11(6):466.

Yang W, Xu T, Qiu P, Xu G. Caveolin-1 promotes pituitary adenoma cells migration and invasion by regulating the interaction between EGR1 and KLF5. Exp Cell Res. 2018;367(1):7–14.

Mai S, Xiao R, Shi L, Zhou X, Yang T, Zhang M, et al. MicroRNA-18a promotes cancer progression through SMG1 suppression and mTOR pathway activation in nasopharyngeal carcinoma. Cell Death Dis. 2019;10(11):819.

Zhou W, Chang A, Zhao H, Ye H, Li D, Zhuo X. Identification of a novel microRNA profile including miR-106b, miR-17, miR-20b, miR-18a and miR-93 in the metastasis of nasopharyngeal carcinoma. Cancer Biomark. 2020;27(4):533–9.

Chen HC, Chen GH, Chen YH, Liao WL, Liu CY, Chang KP, et al. MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma. Br J Cancer. 2009;100(6):1002–11.

Huang H, Sun P, Lei Z, Li M, Wang Y, Zhang HT, et al. miR-145 inhibits invasion and metastasis by directly targeting Smad3 in nasopharyngeal cancer. Tumour Biol. 2015;36(6):4123–31.

Wu J, Yin L, Jiang N, Guo WJ, Gu JJ, Chen M, et al. MiR-145, a microRNA targeting ADAM17, inhibits the invasion and migration of nasopharyngeal carcinoma cells. Exp Cell Res. 2015;338(2):232–8.

Tsao SW, Wang X, Liu Y, Cheung YC, Feng H, Zheng Z, et al. Establishment of two immortalized nasopharyngeal epithelial cell lines using SV40 large T and HPV16E6/E7 viral oncogenes. Biochim Biophys Acta. 2002;1590(1–3):150–8.

Catalanotto C, Cogoni C, Zardo G. MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions. Int J Mol Sci. 2016;17(10):1712.

Du JX, Hagos EG, Nandan MO, Bialkowska AB, Yu B, Yang VW. The E3 ubiquitin ligase SMAD ubiquitination regulatory factor 2 negatively regulates Kruppel-like factor 5 protein. J Biol Chem. 2011;286(46):40354–64.

McLean GW, Carragher NO, Avizienyte E, Evans J, Brunton VG, Frame MC. The role of focal-adhesion kinase in cancer - a new therapeutic opportunity. Nat Rev Cancer. 2005;5(7):505–15.

Parsons JT, Slack-Davis J, Tilghman R, Roberts WG. Focal adhesion kinase: targeting adhesion signaling pathways for therapeutic intervention. Clin Cancer Res. 2008;14(3):627–32.

Zhao J, Guan JL. Signal transduction by focal adhesion kinase in cancer. Cancer Metastasis Rev. 2009;28(1–2):35–49.

Kaczynski J, Cook T, Urrutia R. Sp1- and Kruppel-like transcription factors. Genome Biol. 2003;4(2):206.

Hsu WC, Lee YC, Liang PI, Chang LL, Huang AM, Lin HH, et al. CSF-1 overexpression predicts poor prognosis in upper tract urothelial carcinomas. Dis Markers. 2019;2019:2724948.

Grada A, Otero-Vinas M, Prieto-Castrillo F, Obagi Z, Falanga V. Research techniques made simple: analysis of collective cell migration using the wound healing assay. J Invest Dermatol. 2017;137(2):e11–6.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–8.

Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15–20.

Wong N, Wang X. miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res. 2015;43(Database issue):D146-52.

John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human MicroRNA targets. PLoS Biol. 2004;2(11): e363.

Tokar T, Pastrello C, Rossos AEM, Abovsky M, Hauschild AC, Tsay M, et al. mirDIP 4.1-integrative database of human microRNA target predictions. Nucleic Acids Res. 2018;46(D1):D360–70.

Messeguer X, Escudero R, Farre D, Nunez O, Martinez J, Alba MM. PROMO: detection of known transcription regulatory elements using species-tailored searches. Bioinformatics. 2002;18(2):333–4.

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