Pathophysiology of miR-146a in lung cancer. Prospects of rising of efficiency of targeted therapy
- Authors: Vashchenko V.I.1, Romashova J.E.1, Shabanov P.D.1
-
Affiliations:
- S.M. Kirov Military Medical Academy
- Issue: Vol 19, No 4 (2021)
- Pages: 359-381
- Section: Reviews
- URL: https://journals.eco-vector.com/RCF/article/view/100012
- DOI: https://doi.org/10.17816/RCF194359-381
- ID: 100012
Cite item
Abstract
Lung cancer is a well-known malignant tumor of the respiratory tract, which has caused a significant level of damage to human health. Micro-RNAs (miRNAs) are tiny, non-coding RNA stem-loop structures with a length of roughly 20–25 nucleotides that function as powerful modulators of mRNA and protein products of a gene. miRNAs may modulate many biological processes involving growth, differentiation, proliferation, and cell death and play a key role in the pathogenesis of various types of malignancies. Several accumulating pieces of evidence have proven that miRNA, especially miR-146a, are crucial modulators of innate immune response sequences. A novel and exciting cancer research field has involved miRNA for the detection and suppression of cancer. However, the actual mechanism which is adopted by these miRNA is still unclear. miRNAs have been used as a cancer-associated biomarker in several studies, suggesting their altered expression in various cancers compared to the normal cells. The amount of expression of miRNA can also be used to determine the stage of the disease, aiding in early detection. In breast, pancreatic, and hepatocellular carcinoma, and gastric cancer, cancer cell proliferation and metastasis has been suppressed by miR-146a. Changes in miR-146a expression levels have biomarker importance and possess a high potential as a therapeutic target in lung cancer. It retards epithelial-mesenchymal transition and promotes the therapeutic action of anticancer agents in lung cancer. Studies have also suggested that miR-146a affects gene expression through different signaling pathways viz: TNF-α, NF-κB and MEK-1/2, and JNK-1/2. Further research is required for understanding the molecular mechanisms of miR-146a in lung cancer. The potential role of miR-146a as a diagnostic marker of lung cancer must also be analyzed. This review summarizes the tumor-suppressing, anti-inflammatory, and antichemoresistive nature of miR-146a in lung cancer.
Full Text
About the authors
Vladimir I. Vashchenko
S.M. Kirov Military Medical Academy
Author for correspondence.
Email: vaschenko@yandex.ru
Dr. Sci. (Biol.)
Russian Federation, 6, Academica Lebedeva st., Saint Petersburg, 194044Juliya E. Romashova
S.M. Kirov Military Medical Academy
Email: vladimir-vaschenko@yandex.ru
Head Department of the Blood Center and fabrics
Russian Federation, 6, Academica Lebedeva st., Saint Petersburg, 194044Petr D. Shabanov
S.M. Kirov Military Medical Academy
Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-code: 8974-7477
Dr. Med. Sci. (Pharmacology), Professor
Russian Federation, 6, Academica Lebedeva st., Saint Petersburg, 194044References
- Bogdanova ІM, Boltovskaya MN, Rakhmilevich AL, Artemyeva KA. Key role of tumor-associated macrophages in the progressing and metastasis of tumors. Immunology. 2019;40(4):41–47. (In Russ.) doi: 10.24411/0206-4952-2019-14005
- Laktionov KK, Reutova EV, Ardzinba MS, Mescheryakova NA. Targeted therapy of lung cancer with the ROS1 rearrangement. Medical council. 2017;(6):51–55. (In Russ.) doi: 10.21518/2079-2017.6.51-55
- Liasnikau KA, Shliakhtunou YA. Clinical significance of molecular-genetic markers in the diagnosis and personalization of lung cancer therapy. Vestnik of Vitebsk state medical university. 2020;19(2):7–18. (In Russ.) doi: 10.22263/2312-4156.2020.2.7
- Khvastunov RA, Skrypnikova GV, Usachev AA. Targetnaya terapiya v onkologii. Lekarstvennyi vestnik. 2014;8(4):3–10. (In Russ.)
- Shabanov PD, Vashchenko VI. Biological role of miRNA-146a at virus infections. Modern strategy of search of new safe pharmacological agents for treatment. Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(2):145–174. (In Russ.) doi: 10.17816/RCF192145-174
- Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell. 2005;7(3):211–217. doi: 10.1016/j.ccr.2005.02.013
- Beauchemin N, Arabzadeh A. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer Metastasis Rev. 2013;32(3–4):643–671. doi: 10.1007/s10555-013-9444-6
- Bertoli G, Cava C, Castiglioni I. MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer. Theranostics. 2015;5(10):1122–1143. doi: 10.7150/thno.11543
- Bhaumik D, Scott GK, Schokrpur S, et al. MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8. Aging. 2009;1(4):402–411. doi: 10.18632/aging.100042
- Bleau AM, Redrado M, Nistal-Villan E, et al. miR-146a targets c-met and abolishes colorectal cancer liver metastasis. Cancer Lett. 2018;414:257–267. doi: 10.1016/j.canlet.2017.11.008
- Boeri M, Verri C, Conte D, et al. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc Natl Acad Sci USA. 2011;108(9):3713–3718. doi: 10.1073/pnas.1100048108
- Boldin MP, Teganov KD, Rao DJ, et al. miR-146q is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med. 2011;208(6):1189–1201. doi: 10.1084/jem.20101823
- Bray F, Ferlay J, Soerjomataram I, et al. 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. doi: 10.3322/caac.21492
- Brown KA, Aakre ME, Gorska AE, et al. Induction by transforming growth factor-beta1 of epithelial to mesenchymal transition is a rare event in vitro. Breast Cancer Res. 2004;6(3): R215–R231. doi: 10.1186/bcr778
- Bui N, Woodward B, Johnson A, Husain H. Novel Treatment Strategies for Brain Metastases in Non-small-cell Lung Cancer. Curr Treat Opt Oncol. 2016;17(5):25. doi: 10.1007/s11864-016-0400-x
- Burke JM, Kelenis DP, Kincaid RP, Sullivan CS. A central role for the primary microRNA stem in guiding the position and efficiency of Drosha processing of a viral pri-miRNA. RNA. 2014;20(7):1068–1077. doi: 10.1261/rna.044537.114
- Butkiewicz D, Krześniak M, Gdowicz-Kłosok A, et al. Polymorphisms in EGFR Gene Predict Clinical Outcome in Unresectable Non-Small Cell Lung Cancer Treated with Radiotherapy and Platinum-Based Chemoradiotherapy. Int J Mol Sci. 2021;22(11):5605. doi: 10.3390/ijms22115605
- Chang T-C, Yu D, Lee Y-S, et al. Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet. 2007;40(1):43–50. doi: 10.1038/ng.2007.30
- Chang Y-C, Jan C-I, Peng C-Y, et al. Activation of microRNA- 494-targeting Bmi1 and ADAM10 by silibinin ablates cancer stemness and predicts favourable prognostic value in head and neck squamous cell carcinomas. Oncotarget. 2015;6(27):24002–24016. doi: 10.18632/oncotarget.4365
- Chen G, Umelo IA, Lv S, et al. miR-146a Inhibits Cell Growth, Cell Migration and Induces Apoptosis in Non-Small Cell Lung Cancer Cells. PLoS ONE. 2013;8(3): e60317. doi: 10.1371/journal.pone.0060317
- Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997–1006. doi: 10.1038/cr.2008.282
- Chendrimada TP, Gregory RI, Kumaraswamy E, et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005;436(7051):740–744. doi: 10.1038/nature03868
- Cheung KJ, Ewald AJ. A collective route to metastasis: Seeding by tumor cell clusters. Science. 2016;352(6282):167–169. doi: 10.1126/science.aaf6546
- Cho KB, Cho MK, Lee WY, et al. Overexpression of c-myc induces epithelial mesenchymal transition in mammary epithelial cells. Cancer Lett. 2010;293(2):230–239. doi: 10.1016/j.canlet.2010.01.013
- Condrat CE, Thompson DC, Barbu MG, et al. miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis. Cells. 2020;9(2):276. doi: 10.3390/cells9020276
- Cornett AL, Lutz CS. Regulation of COX-2 expression by miR-146a in lung cancer cells. RNA. 2014;20(9):1419–1430. doi: 10.1261/rna.044149.113
- Conti I, Simioni C, Varano G, et al. MicroRNAs Patterns as Potential Tools for Diagnostic and Prognostic Follow-Up in Cancer Survivorship. Cell. 2021;10(8):2069. doi: 10.3390/cells10082069
- Corral-Fernandez NE, Salgado-Bustamante M, Martinez-Leija ME, et al. Dysregulated miR-155 expression in peripheral blood mononuclear cells from patients with type 2 diabetes. Exp Clin Endocrinol Diabetes. 2013;121(6):347–353. doi: 10.1055/s-0033-1341516
- de Giorgio A, Krell J, Harding V, et al. Emerging Roles of Competing Endogenous RNAs in Cancer: Insights from the Regulation of PTEN. Mol Cell Biol. 2013;33(20):3976–3982. doi: 10.1128/MCB.00683-13
- Deiters A. Small Molecule Modifiers of the microRNA and RNA Interference Pathway. AAPS J. 2009;12(1):51–60. doi: 10.1208/s12248-009-9159-3
- Denli AM, Tops BBJ, Plasterk RHA, et al. Processing of primary microRNAs by the Microprocessor complex. Nature. 2004;432(7014):231–235. doi: 10.1038/nature03049
- Du H, Li Y, Sun R, et al. CEACAM6 promotes cisplatin resistance in lung adenocarcinoma and is regulated by microRNA-146a and microRNA-26a. Thorac Cancer. 2020;11(9):2473–2482. doi: 10.1111/1759-7714.13558
- Eulalio A, Behm-Ansmant I, Schweizer D, Izaurralde E. P-Body Formation is a Consequence, Not the Cause, of RNA-Mediated Gene Silencing. Mol Cell Biol. 2007;27(11):3970–3981. doi: 10.1128/MCB.00128-07
- Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? Nat Rev Genet. 2008;9(2):102–114. doi: 10.1038/nrg2290
- Forloni M, Dogra SK, Dong Y, et al. miR-146a promotes the initiation and progression of melanoma by activating Notch signaling. eLife. 2014;3: e01460. doi: 10.7554/eLife.01460
- Fu J, Rodova M, Nanta R, et al. NPV-LDE-225 (Erismodegib) inhibits epithelial mesenchymal transition and self-renewal of glioblastoma initiating cells by regulating miR-21, miR-128, and miR-200. Neuro-oncology. 2013;15(6):691–706. doi: 10.1093/neuonc/not011
- Garg M. Targeting microRNAs in epithelial-to-mesenchymal transition-induced cancer stem cells: therapeutic approaches in cancer. Expert Opin Ther Targets. 2015;19(2):285–297. doi: 10.1517/14728222.2014.975794
- Garzon R, Marcucci G, Targeting CCM. MicroRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 2010;9(10):775–789. doi: 10.1038/nrd3179
- Ghany S, Riemke P, Schonheit J, et al. Macrophage development from HSCs requires PU.1-coordinated microRNA expression. Blood. 2011;118(8):2275–2284. doi: 10.1182/blood-2011-02-335141
- Ghuwalewala S, Ghatak D, Das S, et al. MiR-146a-dependent regulation of CD24/AKT/β-catenin axis drives cancer stem cell phenotype in oral squamous cell carcinoma. bioRxiv. 2019:429068. doi: 10.1101/429068
- Gibbons DL, Lin W, Creighton CJ, et al. Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Genes Dev. 2009;23(18):2140–2151. doi: 10.1101/gad.1820209
- Gilad S, Lithwick-Yanai G, Barshack I, et al. Classification of the Four Main Types of Lung Cancer Using a microRNA-Based Diagnostic Assay. J Mol Diagn. 2012;14(5):510–517. doi: 10.1016/j.jmoldx.2012.03.004
- Gregory RI, Yan K-P, Amuthan G, et al. The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004;432(7014):235–240. doi: 10.1038/nature03120
- Gomes M, Teixeira AL, Coelho A, et al. The Role of Inflammation in Lung Cancer. In: B.B. Aggarwal, B. Sung, S.C. Gupta, editors. Advances in Experimental Medicine and Biology. Switzerland, Basel: Springer Basel, 2014. P. 1–23. doi: 10.1007/978-3-0348-0837-8_1
- Hagemann T, Wilson J, Kulbe H, et al. Macrophages Induce Invasiveness of Epithelial Cancer Cells Via NF-κB and JNK. J Immunol. 2005;175(2):1197–1205. doi: 10.4049/jimmunol.175.2.1197
- Han J, Lee Y, Yeom K-H, et al. Molecular Basis for the Recognition of Primary microRNAs by the Drosha-DGCR8 Complex. Cell. 2006;125(5):887–901. doi: 10.1016/j.cell.2006.03.043
- Han J. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004;18(24):3016–3027. doi: 10.1101/gad.1262504
- Han W, Du X, Liu M, et al. Increased expression of long non-coding RNA SNHG16 correlates with tumor progression and poor prognosis in non-small cell lung cancer. Int J Biol Macromol. 2019;121:270–278. doi: 10.1016/j.ijbiomac.2018.10.004
- Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell. 2011;144(5):646–674. doi: 10.1016/j.cell.2011.02.013
- Hata A, Kashima R. Dysregulation of microRNA biogenesis machinery in cancer. Crit Rev Biochem Mol Biol. 2016;51(3):121–134. doi: 10.3109/10409238.2015.1117054
- Hay ED, Zuk A. Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis. 1995;26(4):678–690. doi: 10.1016/0272-6386(95)90610-x
- He H, Xu C, Zheng L, et al. Polyphyllin VII induces apoptotic cell death via inhibition of the PI3K/Akt and NF-κB pathways in A549 human lung cancer cells. Mol Med Rep. 2020;21(2):597–606. doi: 10.3892/mmr.2019.10879
- Heuberger J, Birchmeier W. Interplay of cadherin-mediated cell adhesion and canonical Wnt signaling. Cold Spring Harb Perspect Biol. 2010;2(2): a002915. doi: 10.1101/cshperspect.a002915
- Huang WT, He RQ, Li XJ, et al. miR-146a-5p targets TCSF and influences cell growth and apoptosis to repress NSCLC progression. Oncol Rep. 2019;41(4):2226–2240. doi: 10.3892/or.2019.7030
- Jiang P, Jia W, Wei X, et al. MicroRNA-146a regulates cisplatin-resistance of non-small cell lung cancer cells by targeting NF-kappaB pathway. Int J Clin Exp Pathol. 2017;10(12):11545–11553.eCollection 2017.
- Jiang WG, Sanders AJ, Katoh M, et al. Tissue invasion and metastasis: Molecular, biological and clinical perspectives. Semin Cancer Biol. 2015;35(Suppl): S244–S275. doi: 10.1016/j.semcancer.2015.03.008
- Jung YY, Shanmugam MK, Narula AS, et al. Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model. Cancers. 2019;11(1):49. doi: 10.3390/cancers11010049
- Iacona JR, Monteleone NJ, Lutz CS. miR-146a suppresses 5-lipoxygenase activating protein (FLAP) expression and Leukotriene B4 production in lung cancer cells. Oncotarget. 2018;9(42):26751–26769. doi: 10.18632/oncotarget.25482
- Kim J, Yao F, Xiao Z, et al. MicroRNAs and metastasis: Small RNAs play big roles. Cancer Metastasis Rev. 2018;37(1):5–15. doi: 10.1007/s10555-017-9712-y
- Kim YK, Kim B, Kim VN. Re-evaluation of the roles of DROSHA, Export in 5, and DICER in microRNA biogenesis. Proc Natl Acad Sci USA. 2016;113(13): E1881–Е1889. doi: 10.1073/pnas.1602532113
- Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov. 2004;3(8):711–716. doi: 10.1038/nrd1470
- Ko J-H, Nam D, Um J-Y, et al. Bergamottin Suppresses Metastasis of Lung Cancer Cells through Abrogation of Diverse Oncogenic Signaling Cascades and Epithelial-to-Mesenchymal Transition. Моlecules. 2018;23(7):1601. doi: 10.3390/молекулы 23071601
- Kong W, Yang H, He L, et al. MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol. 2008;28(22):6773–6784. doi: 10.1128/MCB.00941-08
- Kotha NV, Cherry DR, Bryant AK, et al. Prognostic utility of pretreatment neutrophil-lymphocyte ratio in survival outcomes in localized non-small cell lung cancer patients treated with stereotactic body radiotherapy: Selection of an ideal clinical cutoff point. Clin Transl Radiat Oncol. 2021;28:133–140. doi: 10.1016/j.ctro.2021.03.010
- Kulis M, Esteller M. 2-DNA Methylation and Cancer. Advances and Genetics. 2010;70:27–56. doi: 10.1016/B978-0-12-380866-0.60002-2
- Kumaraswamy E, Wendt KL, Augustine LA, et al. BRCA1 regulation of epidermal growth factor receptor (EGFR) expression in human breast cancer cells involves microRNA-146a and is critical for its tumor suppressor function. Oncogene. 2014;34(33):4333–4346. doi: 10.1038/onc.2014.363
- Kumarswamy R, Mudduluru G, Ceppi P, et al. MicroRNA-30a inhibits epithelial-to-mesenchymal transition by targeting Snai1 and is downregulated in non-small cell lung cancer. Int J Cancer. 2012;130(9):2044–2053. doi: 10.1002/ijc.26218
- Labbaye C, Spinello I, Quaranta MT, et al. A three-step pathway comprising PLZF/miR-146a/CXCR4 controls megakaryopoiesis. Nat Cell Biol. 2008;10(7):788–800. doi: 10.1038/ncb1741
- Lagos-Quintana M, Rauhut R, Yalcin A, et al. Identification of Tissue-Specific MicroRNAs from Mouse. Curr Biol. 2002;12(9):735–739. doi: 10.1016/S0960-9822(02)00809-6
- Lamar JM, Xiao Y, Norton E, et al. SRC-tyrosine kinase activates the YAP/TAZ axis and thereby drives tumor growth and metastasis. J Biol Chem. 2019;294(7):2302–2317. doi: 10.1074/jbc.RA118.004364
- Lambert KA, Roff AN, Panganiban RP, et al. MicroRNA-146a is induced by inflammatory stimuli in airway epithelial cells and augments the anti-inflammatory effects of glucocorticoids. PLoS ONE. 2018;13(10):e0205434. doi: 10.1371/journal.pone.0205434
- Landi MT, Zhao Y, Rotunno M, et al. MicroRNA Expression Differentiates Histology and Predicts Survival of Lung Cancer. Clin Cancer Res. 2010;16(2):430–441. doi: 10.1158/1078-0432.CCR-09-1736
- Larner-Svensson HM, Williams AE, Tsitsiou E, et al. Pharmacological studies of the mechanism and function of interleukin-1β-induced miRNA-146a expression in primary human airway smooth muscle. Respir Res. 2010;11(1):1–13. doi: 10.1186/1465-9921-11-68
- Lebanony D, Benjamin H, Gilad S, et al. Diagnostic Assay Based on hsa-miR-205 Expression Distinguishes Squamous From Nonsquamous Non-Small-Cell Lung Carcinoma. J Clin Oncol. 2009;27(12):2030–2037. doi: 10.1200/JCO.2008.19.4134
- Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–854. doi: 10.1016/0092-8674(93)90529-Y
- Lee Y, Ahn C, Han J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425(6956):415–419. doi: 10.1038/nature01957
- Li B, Ren S, Li X, et al. MiR-21 overexpression is associated with acquired resistance of EGFR-TKI in non-small cell lung cancer. Lung Cancer. 2014;83(2):146–153. doi: 10.1016/j.lungcan.2013.11.003
- Li J, Zhang J, Xie F, et al. Macrophage migration inhibitory factor promotes Warburg effect via activation of the NF-κB/HIF-1α pathway in lung cancer. Int J Mol Med. 2017;41(2):1062–1068. doi: 10.3892/ijmm.2017.3277
- Li M-W, Gao L, Dang Y-W, et al. Protective potential of miR-146a-5p and its underlying molecular mechanism in diverse cancers: A comprehensive meta-analysis and bioinformatics analysis. Cancer Cell Int. 2019;19:1–21. doi: 10.1186/s12935-019-0886-y
- Li Y-L, Wang J, Zhang C-Y, et al. MiR-146a-5p inhibits cell proliferation and cell cycle progression in NSCLC cell lines by targeting CCND1 and CCND2. Oncotarget. 2016;7(37):59287–59298. doi: 10.18632/oncotarget.11040
- Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol. 2005;7(7):719–723. doi: 10.1038/ncb1274
- Liu L, Wan C, Zhang W, et al. MiR-146a regulates PM1-induced inflammation via NF-kappaB signaling pathway in BEAS-2B cells. Environ Toxicol. 2018;33(7):743–751. doi: 10.1002/tox.22561
- Liu R, Liu C, Chen D, et al. FOXP3 Controls an miR-146/NF-κB Negative Feedback Loop That Inhibits Apoptosis in Breast Cancer Cells. Cancer Res. 2015;75(8):1703–1713. doi: 10.1158/0008-5472.CAN-14-2108
- Lorenz DA, Garner AL. Approaches for the Discovery of Small Molecule Ligands Targeting microRNAs. In: Bernstein PR, Garner AL, Georg GI, et al. editors. Topics in Medicinal Chemistry. USA, New York: Springer International Publishing, 2017. P. 79–110. doi: 10.1007/7355_2017_3
- Madhavan D, Cuk K, Burwinkel B, Yang R. Cancer diagnosis and prognosis decoded by blood-based circulating microRNA signatures. Front Genet. 2013;4:116. doi: 10.3389/fgene.2013.00116
- Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704–715. doi: 10.1016/j.cell.2008.03.027
- McClure JJ, Li X, Chou CJ. Advances and Challenges of HDAC Inhibitors in Cancer Therapeutics. Adv Cancer Res. 2018;138: 183–211. doi: 10.1016/bs.acr.2018.02.006
- Mehta M, Tewari D, Gupta G, et al. Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases. Chem Biol Interact. 2019;308:206–215. doi: 10.1016/j.cbi.2019.05.028
- Mohamed RH, Pasha HF, Gad DM, Toam MM. miR-146a and miR-196a-2 genes polymorphisms and its circulating levels in lung cancer patients. J Biochem. 2019;166(4):323–329. doi: 10.1093/jb/mvz044
- Molina JR, Yang P, Cassivi SD, et al. Non-Small Cell Lung Cancer: Epidemiology, Risk Factors, Treatment, and Survivorship. Mayo Clin Proc. 2008;83(5):584–594. doi: 10.1016/S0025-6196(11)60735-0
- Mongroo PS, Rustgi AK. The role of the miR-200 family in epithelial-mesenchymal transition. Cancer Biol Ther. 2010;10(3): 219–222. doi: 10.4161/cbt.10.3.12548
- Oft M, Peli J, Rudaz C, et al. TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev. 1996;10(19):2462–2477. doi: 10.1101/gad.10.19.2462
- Opalinska JB, Bersenev A, Zhang Z, et al. MicroRNA expression in maturing megakaryocytes. Blood. 2010;116(23): e128–e138. doi: 10.1182/blood-2010-06-292920
- Pang L, Lu J, Huang J, et al. Upregulation of miR-146a increases cisplatin sensitivity of the non-small cell lung cancer A549 cell line by targeting JNK-2. Oncol Lett. 2017;14(6):7745–7752. doi: 10.3892/ol.2017.7242
- Park DH, Jeon HS, Lee SY, et al. MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2. Int J Oncol. 2015;47(4):1545–1553. doi: 10.3892/ijo.2015.3111
- Pavel AB, Campbell JD, Liu G, et al. Alterations in Bronchial Airway miRNA Expression for Lung Cancer Detection. Cancer Prev Res. 2017;10(11):651–659. doi: 10.1158/1940-6207.CAPR-17-0098
- Pérez-García EI, Meza-Sosa KF, López-Sevilla Y, et al. Merlin negative regulation by miR-146a promotes cell transformation. Biochem Biophys Res Commun. 2015;468(4):594–600. doi: 10.1016/j.bbrc.2015.10.156
- Perry MM, Moschos SA, Williams AE, et al. Rapid Changes in MicroRNA-146a Expression Negatively Regulate the IL-1β-Induced Inflammatory Response in Human Lung Alveolar Epithelial Cells. J Immunol. 2008;180(8):5689–5698. doi: 10.4049/jimmunol.180.8.5689
- Pritchard CC, Cheng HH, Tewari M. MicroRNA profiling: Approaches and considerations. Nat Rev Genet. 2012;13(5):358–369. doi: 10.1038/nrg3198
- Ren Y-G, Zhou X-M, Cui Z-G, Hou G. Effects of common polymorphisms in miR-146a and miR-196a2 on lung cancer susceptibility: A meta-analysis. J Thorac Dis. 2016;8(6):1297–1305. doi: 10.21037/jtd.2016.05.02
- Richardson CM, Sharma RA, Cox G, O’Byrne KJ. Epidermal growth factor receptors and cyclooxygenase-2 in the pathogenesis of non-small cell lung cancer: Potential targets for chemoprevention and systemic therapy. Lung Cancer. 2003;39(1):1–13. doi: 10.1016/S0169-5002(02)00382-3
- Rieber M, Strasberg Rieber M. DN-R175H p53 mutation is more effective than p53 interference in inducing epithelial disorganization and activation of proliferation signals in human carcinoma cells: role of E-cadherin. Int J Cancer. 2009;125(7):1604–1612. doi: 10.1002/ijc.24512
- Rosenfeld N, Aharonov R, Meiri E, et al. MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol. 2008;26:462–469. doi: 10.1038/nbt1392
- Ryasen GW, Starczynowski DT. Deregulation of microRNA in myelodysplastic syndrome. Leukemia. 2012;26(1):13–22. doi: 10.1038/leu.2011.221
- Qiu H, Xie Z, Tang W, et al. Association between microRNA-146a, -499a and -196a-2 SNPs and non-small cell lung cancer: a case-control study involving 2249 subjects. Biosci Rep. 2021;41(2): BSR20201158. doi: 10.1042/BSR20201158
- Qi P, Li Y, Liu X, et al. Cryptotanshinone Suppresses Non-Small Cell Lung Cancer via microRNA-146a-5p/EGFR Axis. Int J Biol Sci. 2019;15(5):1072–1079. doi: 10.7150/ijbs.31277
- Qu J, Chen X, Sun Y-Z, et al. In Silico Prediction of Small Molecule-miRNA Associations Based on the HeteSim Algorithm. Mol Ther Nucleic Acids. 2019;14:274–286. doi: 10.1016/j.omtn.2018.12.002
- Saba R, Sorensen DL, Booth SA. MicroRNA-146a: A Dominant, Negative Regulator of the Innate Immune Response. Front Immunol. 2014;5:578. doi: 10.3389/fimmu.2014.00578
- Said NA, Williams ED. Growth factors in induction of epithelial-mesenchymal transition and metastasis. Cells Tissues Organs. 2011;193(1–2):85–97. doi: 10.1159/000320360
- Saito RA, Watabe T, Horiguchi K, et al. Thyroid transcription factor-1 inhibits transforming growth factor-beta-mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells. Cancer Res. 2009;69(7):2783–2791. doi: 10.1158/0008-5472.CAN-08-3490
- Sanchez NC, Medrano-Jimenez E, Aguilar-Leon D, et al. Tumor Necrosis Factor-Induced miR-146a Upregulation Promotes Human Lung Adenocarcinoma Metastasis by Targeting Merlin. DNA Cell Biol. 2020;39(3):484–497. doi: 10.1089/dna.2019.4620
- Samec M, Liskova A, Koklesova L, et al. Flavonoids against the Warburg phenotype – Concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism. EPMA J. 2020;11(3):377–398. doi: 10.1007/s13167-020-00217-y
- Sato M, Shames DS, Hasagawa Y. Emerging evidence of epithelial-to-mesenchymal transition in lung cancinogenesis. Respirology. 2012;17(7):1048–1059. doi: 10.1111/j.1440-1843.2012.02173.x
- Shahriar A, Ghaleh-Aziz Shiva G, Ghader B, et al. The dual role of miR-146a in metastasis and disease progression. Biomed Pharm. 2020;126:110099. doi: 10.1016/j.biopha.2020.110099
- Saunders NA, Simpson F, Thompson EW, et al. Role of intratumoural heterogeneity in cancer drug resistance: Molecular and clinical perspectives. Embo Mol Med. 2012;4(8):675–684. doi: 10.1002/emmm.201101131
- Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 2007;7(3):169–181. doi: 10.1038/nrc2088
- Shi L, Xu Z, Wu G, et al. Up-regulation of miR-146a increases the sensitivity of non-small cell lung cancer to DDP by downregulating cyclin J. BMC Cancer. 2017;17(1):1–14. doi: 10.1186/s12885-017-3132-9
- Shen K-H, Hung J-H, Chang C-W, et al. Solasodine inhibits invasion of human lung cancer cell through downregulation of miR-21 and MMPs expression. Chem Biol Interact. 2017;268:129–135. doi: 10.1016/j.cbi.2017.03.005
- Singh A, Settleman J. EMT, cancer stem cells and drug resistance: An emerging axis of evil in the war on cancer. Oncogene. 2010;29(34):4741–4751. doi: 10.1038/onc.2010.215
- Sodhi KK, Bahl C, Singh N, et al. Functional genetic variants in pre-miR-146a and 196a2 genes are associated with risk of lung cancer in North Indians. Future Oncol. 2015;11(15):2159–2173. doi: 10.2217/fon.15.143
- Stahlhut C, Slack FJ. Combinatorial Action of MicroRNAs let-7 and miR-34 Effectively Synergizes with Erlotinib to Suppress Non-small Cell Lung Cancer Cell Proliferation. Cell Cycle. 2015;14(13):2171–2180. doi: 10.1080/15384101.2014.1003008
- Starczynowski DT, Kuchenbauer F, Wegrzyn J, et al. MicroRNA-146a disrupts hematopoietic differentiation and survival. Exp Hematol. 2011;39(2):167–178. doi: 10.1016/j.exphem.2010.09.011
- Starczynowski DT, Kukenbauer F, Arigiropoulos B, et al. Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype. Nature Med. 2010;16(1):49–58. doi: 10.1038/nm.2054
- Stenvang J, Petri A, Lindow M, et al. Inhibition of microRNA function by antimiR oligonucleotides. Silence. 2012;3(1):1–17. doi: 10.1186/1758-907X-3-1
- Stuckrath I, Rack B, Janni W, et al. Aberrant plasma levels of circulating miR-16, miR-107, miR-130a and miR-146a are associated with lymph node metastasis and receptor status of breast cancer patients. Oncotarget. 2015;6(15):13387–13401. doi: 10.18632/oncotarget.3874
- Sun M, Fang S, Li W, et al. Associations of miR-146a and miR-146b expression and clinical characteristics in papillary thyroid carcinoma. Cancer Biomark. 2015;15(1):33–40. doi: 10.3233/CBM-140431
- Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA. 2006;103(33):12481–12486. doi: 10.1073/pnas.0605298103
- Tan W, Liao Y, Qiu Y, et al. miRNA 146a promotes chemotherapy resistance in lung cancer cells by targeting DNA damage inducible transcript 3 (CHOP). Cancer Lett. 2018;428:55–68. doi: 10.1016/j.canlet.2018.04.028
- Treiber T, Treiber N, Meister G. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat Rev Mol Cell Biol. 2019;20:5–20. doi: 10.1038/s41580-018-0059-1
- Turchinovich A, Weiz L, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011;39(16):7223–7233. doi: 10.1093/nar/gkr254
- Vang S, Wu HT, Fischer A, et al. Identification of ovarian cancer metastatic miRNAs. PLoS ONE. 2013;8(3):e58226. doi: 10.1371/journal.pone.0058226
- Velagapudi SP, Vummidi BR, Disney MD. Small molecule chemical probes of microRNA function. Curr Opin Chem Biol. 2015;24:97–103. doi: 10.1016/j.cbpa.2014.10.024
- Viswanathan SR, Daley GQ. Lin28: A MicroRNA Regulator with a Macro Role. Cell. 2010;140(4):445–449. doi: 10.1016/j.cell.2010.02.007
- Wani JA, Majid SM, Khan A, et al. Clinico-Pathological Importance of miR-146a in Lung Cancer. Diagnostics (Basel). 2021;11(2):274. doi: 10.3390/diagnostics11020274
- Wang C-C, Chen X, Qu J, et al. RFSMMA: A New Computational Model to Identify and Prioritize Potential Small Molecule–MiRNA Associations. J Chem Inf Model. 2019;59(4):1668–1679. doi: 10.1021/acs.jcim.9b00129
- Wang RJ, Zheng YH, Wang P, Zhang JZ. Serum miR-125a-5p, miR-145 and miR-146a as diagnostic biomarkers in non-small cell lung cancer. Int J Clin Exp Pathol. 2015;8(1):765–771.eCollection 2015.
- Wang X, Gao H, Ren L, et al. Demethylation of the miR-146a promoter by 5-Aza-2'-deoxycytidine correlates with delayed progression of castration-resistant prostate cancer. BMC Cancer. 2014;14:1–11. doi: 10.1186/1471-2407-14-308
- Wang W-M, Liu J-C. Effect and molecular mechanism of mir-146a on proliferation of lung cancer cells by targeting and regulating MIF gene. Asian Pac J Trop Med. 2016;9(8):806–811. doi: 10.1016/j.apjtm.2016.06.001
- Watashi K, Yeung ML, Starost MF, et al. Identification of Small Molecules That Suppress MicroRNA Function and Reverse Tumorigenesis. J Biol Chem. 2010;285(32):24707–24716. doi: 10.1074/jbc.M109.062976
- Wei Y, Zou Z, Becker N, et al. EGFR-Mediated Beclin 1 Phosphorylation in Autophagy Suppression, Tumor Progression, and Tumor Chemoresistance. Cell. 2013;154(6):1269–1284. doi: 10.1016/j.cell.2013.08.015
- Wiggins JF, Ruffino L, Kelnar K, et al. Development of a Lung Cancer Therapeutic Based on the Tumor Suppressor microRNA-34. Cancer Res. 2010;70(14):5923–5930. doi: 10.1158/0008-5472.CAN-10-0655
- Woodhouse EC, Chuaqui RF, Liotta LA. General mechanisms of metastasis. Cancer. 1997;80(8):1529–1537. doi: 10.1002/(sici)1097–0142(19971015)80:8+<1529:: aid-cncr2>3.3.co;2-#
- Wu C, Cao Y, He Z, et al. Serum Levels of miR-19b and miR-146a as Prognostic Biomarkers for Non-Small Cell Lung Cancer. Tohoku J Exp Med. 2014;232(2):85–95. doi: 10.1620/tjem.232.85
- Wu K, He J, Pu W, Peng Y. The Role of Exportin-5 in microRNA Biogenesis and Cancer. Genomics Proteomics Bioinformatics. 2018;16(2):120–126. doi: 10.1016/j.gpb.2017.09.004
- Xiao W, Zhong Y, Wu L, et al. Prognostic value of microRNAs in lung cancer: A systematic review and meta-analysis. Mol Clin Oncol. 2018;10(1):67–77. doi: 10.3892/mco.2018.1763
- Yang H, Sun B, Xu K, et al. Pharmaco-transcriptomic correlation analysis reveals novel responsive signatures to HDAC inhibitors and identifies Dasatinib as a synergistic interactor in small-cell lung cancer. EBioМеdicine. 2021;69:103457. doi: 10.1016/j.ebiom.2021.103457
- Yin J, Zhao J, Hu W, et al. Disturbance of the let-7/LIN28 double-negative feedback loop is associated with radio- and chemo-resistance in non-small cell lung cancer. PLoS ONE. 2017;12(2): e0172787. doi: 10.1371/journal.pone.0172787
- Yoon K-A, Yoon H, Park S, et al. The prognostic impact of microRNA sequence polymorphisms on the recurrence of patients with completely resected non-small cell lung cancer. J Thorac Cardiovasc Surg. 2012;144(4):794–807. doi: 10.1016/j.jtcvs.2012.06.030
- Yuwen DL, Sheng BB, Liu J, et al. MiR-146a-5p level in serum exosomes predicts therapeutic effect of cisplatin in non-small cell lung cancer. Eur Rev Med Pharm Sci. 2017;21(11):2650–2658.
- Zaman MS, Chen Y, Deng G, et al. The functional significance of microRNA-145 in prostate cancer. Br J Cancer. 2010;103(2):256–264. doi: 10.1038/sj.bjc.6605742
- Zhang Y, Du H, Li Y, et al. Elevated TRIM23 expression predicts cisplatin resistance in lung adenocarcinoma. Cancer Sci. 2020;111(2):637–646. doi: 10.1111/cas.14226
- Zhang Z, Zhang Y, Sun XX, et al. microRNA-146a inhibits cancer metastasis by downregulating VEGF through dual pathways in hepatocellular carcinoma. Mol Cancer. 2015;14:1–15. doi: 10.1186/1476-4598-14-5
- Zhao JL, Rao DS, Boldin MP, et al. NF-κB dysregulation in microRNAa-deficient mice drives the development of myeloid malignancies. Proc Natl Acad Sci USA. 2011;108(22):9184–9189. doi: 10.1073/pnas.1105398108
- Zheng D, Haddadin S, Wang Y, et al. Plasma microRNAs as novel biomarkers for early detection of lung cancer. Int J Clin Exp Pathol. 2011;4(6):575–586.
- Zeng Y, Yi R, Cullen BR. Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. Embo J. 2004;24(1):138–148. doi: 10.1038/sj.emboj.7600491
- Zhong H, Lu J, Jing S, et al. Low-dose rituximab lowers serum Exosomal miR-150-5p in AChR-positive refractory myasthenia gravis patients. J Neuroimmunol. 2020;348:577383. doi: 10.1016/j.jneuroim.2020.577383
- Zhong M, Ma X, Sun C, Chen L. MicroRNAs reduce tumor growth and contribute to enhance cytotoxicity induced by gefitinib in non-small cell lung cancer. Chem Biol Interact. 2010;184(3):431–438. doi: 10.1016/j.cbi.2010.01.025
- Zhou Y-X, Zhao W, Mao L-W, et al. Long non-coding RNA NIFK-AS1 inhibits M2 polarization of macrophages in endometrial cancer through targeting miR-146a. Int J Biochem Cell Biol. 2018;104:25–33. doi: 10.1016/j.biocel.2018.08.017
- Zhu X, Li Y, Xie C, et al. miR-145 sensitizes ovarian cancer cells to paclitaxel by targeting Sp1 and Cdk6. Int J Cancer. 2014;135(6):1286–1296. doi: 10.1002/ijc.28774
- Zucker S, Hymowitz M, Rollo EE, et al. Tumorigenic Potential of Extracellular Matrix Metalloproteinase Inducer. Am J Pathol. 2001;158(6):1921–1928. doi: 10.1016/S0002-9440(10)64660-3