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http://dx.doi.org/10.12717/DR.2014.18.4.197

A New Paradigm to Mitigate Osteosarcoma by Regulation of MicroRNAs and Suppression of the NF-${\kappa}B$ Signaling Cascade  

Mongre, Raj Kumar (Laboratory of Animal Genetic Engineering and Stem Cell Biology, Dept. of Animal Biotechnology, Faculty of Biotechnology, Jeju National University)
Sodhi, Simrinder Singh (Laboratory of Animal Genetic Engineering and Stem Cell Biology, Dept. of Animal Biotechnology, Faculty of Biotechnology, Jeju National University)
Ghosh, Mrinmoy (Laboratory of Animal Genetic Engineering and Stem Cell Biology, Dept. of Animal Biotechnology, Faculty of Biotechnology, Jeju National University)
Kim, Jeong Hyun (Laboratory of Animal Genetic Engineering and Stem Cell Biology, Dept. of Animal Biotechnology, Faculty of Biotechnology, Jeju National University)
Kim, Nameun (Laboratory of Animal Genetic Engineering and Stem Cell Biology, Dept. of Animal Biotechnology, Faculty of Biotechnology, Jeju National University)
Sharma, Neelesh (Division of Veterinary Medicine, Faculty of Veterinary Science & Animal Husbandry, Sher-e-kashmir University of Agricultural Sciences & Technology of Jammu)
Jeong, Dong Kee (Laboratory of Animal Genetic Engineering and Stem Cell Biology, Dept. of Animal Biotechnology, Faculty of Biotechnology, Jeju National University)
Publication Information
Development and Reproduction / v.18, no.4, 2014 , pp. 197-212 More about this Journal
Abstract
Osteosarcoma (OS) is one of the most common malignant primary bone tumors and NF-${\kappa}B$ appears to play a causative role, but the mechanisms are poorly understood. OS is one of the pleomorphic, highly metastasized and invasive neoplasm which is capable to generate osteoid, osteoclast and osteoblast matrix. Its high incidence has been reported in adolescent and children. Cell signal cascade is the pivotal functional mechanism acquired during the differentiation, proliferation, growth and survival of the cells in neoplasm including OS. The major limitation to the success of chemotherapy in OS is the development of multidrug resistance (MDR). Answers to all such queries might come from the knock-in experiments in which the combined approach of miRNAs with NF-${\kappa}B$ pathway is put into use. Abnormal miRNAs can modulate several epigenetical switching as a hallmark of number of diseases via different cell signaling. Studies on miRNAs have opened up the new avenues for both the diagnosis and treatment of cancers including OS. Collectively, through the present study an attempt has been made to establish a new systematic approach for the investigation of microRNAs, bio-physiological factors and their target pairs with NF-${\kappa}B$ to ameliorate oncogenesis with the "bridge between miRNAs and NF-${\kappa}B$". The application of NF-${\kappa}B$ inhibitors in combination with miRNAs is expected to result in a more efficient killing of the cancer stem cells and a slower or less likely recurrence of cancer.
Keywords
Targetome; GWAS; BBNM; Histeotypic neoplasia; RANK; miR;
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1 Kaltschmidt B, Widera D, Kaltschmidt C (2005) Signaling via NF-kappaB in the nervous system. Biochim Biophys Acta 1745:287-299.   DOI   ScienceOn
2 Kansara M, Thomas DM (2007) Molecular pathogenesis of osteosarcoma. DNA Cell Biol 26:1-18.   DOI   ScienceOn
3 Karin M (2009) NF-kappaB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol 1:1-14.
4 Karlsson EK, Sigurdsson S, Ivansson E, Thomas R, Elvers I, Wright J, Howald C, Tonomura N, Perloski M, Swofford R, Biagi T, Fryc S, Anderson N, Courtay-Cahen C, Youell L, Ricketts SL, Mandlebaum S, Rivera P, von Euler H, Kisseberth, WC, London CA, Lander ES, Couto G, Comstock K, Starkey MP, Modiano JF, Breen M, Lindblad-Toh K (2013) Genome-wide analyses implicate 33 loci inheritable dog Osteosarcoma, including regulatory variants near CDKN2A/B. Genome Biol 14: 1-15.   DOI   ScienceOn
5 Kelly AD, Haibe-Kains B, Janeway KA, Hill KE, Howe E, Goldsmith J, Kurek K, Perez-Atayde AR, Francoeur N, Fan JB, April C, Schneider H, Gebhardt MC, Culhane A, Quackenbush J, Spentzos D (2013) MicroRNA paraffinbased studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32. Genome Med 5:1-12.   DOI   ScienceOn
6 Kim SW, Ramasamy K, Bouamar H, Lin AP, Jiang D, Aguiar RC (2012) MicroRNAs miR-125a and miR-125b constitutively activate the NF-$\kappa$B pathway by targeting the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20). Proc Natl Acad Sci USA 109: 7865-7870.   DOI
7 Kobayashi E, Hornicek FJ, Duan Z (2012) MicroRNA involvement in osteosarcoma. Sarcoma 2012:1-8.
8 Li T, Guan J, Li S, Zhang X, Zheng X (2014) HSCARG downregulates NF-$\kappa$B signaling by interacting with USP7 and inhibiting NEMO ubiquitination. Cell Death Dis 5:e1229.   DOI   ScienceOn
9 Lin A, Liu ZG (2008) Cell signaling review series. Cell Res 18:327.   DOI   ScienceOn
10 Lin SC, Wortis HH, Stavnezer J (1998) The ability of CD40L, but not lipopolysaccharide, to initiate immuneglobulin switching to immunoglobulin G1 is explained by differential induction of NF-kappaB/Rel proteins. Mol Cell Biol 18:5523-5532.
11 Liu CJ, Tsai MM, Tu HF, Lui MT, Cheng HW, Lin SC (2013) MiR-196a overexpression and miR-196a2 gene polymorphism are prognostic predictors of oral carcinomas. Ann. Surg. Oncol 20:S406-S414.
12 Liu ZL, Mao JH, Peng AF, Yin QS, Zhou Y, Long XH, Huang SH (2013) Inhibition of fatty acid synthase suppresses osteosarcoma cell invasion and migration via downregulation of the PI3K/Akt signaling pathway in vitro. Mol Med Rep 7:608-12.
13 Longhi A, Errani C, De Paolis M, Mercuri M, Bacci G (2006) Primary bone OS in the pediatric age: state of threat. Cancer Treat Rev 32:423-436.   DOI   ScienceOn
14 Mattson MP, Camandola S (2001) NF-$\kappa$B in neuronal plasticity and neurodegenerative disorders. J of Clin Invest 107:247-254.   DOI   ScienceOn
15 Mendell JT, Olson EN (2012) MicroRNAs in stress signaling and human disease. Cell 148:1172-1187.   DOI   ScienceOn
16 Minakhina S, Steward R (2006) Nuclear factor-kappa B pathways in Drosophila. Oncogene 25:6749-6757.   DOI   ScienceOn
17 Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105:10513-10518.   DOI   ScienceOn
18 Namlos HM, Meza-Zepeda LA, Baroy T, Ostensen IH, Kresse SH, Kuijjer ML, Serra M, Burger H, Cleton-Jansen AM, Myklebost O (2012) Modulation of the Osteosarcoma expression phenotype by microRNAs. PLoS One 7:e48086.   DOI
19 National Institute of Health. (2014) Understanding Cancer Series - National Cancer Institute. Available: http://www.cancer.gov/cancertopics/understandingcancer/cancer/
20 O'Sullivan B, Thompson A, Thomas R (2007) NF-$\kappa$B as a therapeutic target in autoimmune disease. Expert Opin Ther Targets 11:111-122.   DOI   ScienceOn
21 Oeckinghaus A, Hayden MS, Ghosh S (2011) Crosstalk in NF-$\kappa$B signaling pathways. Nature Immun 12:695-708.   DOI   ScienceOn
22 Olarerin-George AO, Anton L, Hwang YC, Elovitz MA, Hogenesch JB (2013) A functional genomics screen for microRNA regulators of NF-kappaB signaling. BMC Biol 11:1-16.   DOI
23 Ougang L, Liu P, Yang S, Ye S, Xu W, Liu X, (2013) A three-plasma miRNA signature serves as novel biomarker for osteosarcoma. Med Oncol 30:340.   DOI   ScienceOn
24 Papa S, Bubici C, Zazzeroni F, Franzoso G (2009) Mechanisms of liver disease: The crosstalk between the NF-$\kappa$B and JNK pathways. Biol Chem 390: 965-976.
25 Perkins ND (2007) Integrating cell-signaling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8:49-62.   DOI   ScienceOn
26 Pham CG, Bubici C, Zazzeroni F, Knabb JR, Papa S, Kuntzen C, Franzoso G (2007) Upregulation of Twist-1 by NF-kappaB blocks cytotoxicity induced by chemotherapeutic drugs. Mol Cell Biol 27:3920-3935.   DOI   ScienceOn
27 Poos K, Smida J, Nathrath M, Maugg D, Baumhoer D, Korsching E (2013) How MicroRNA and transcription factor co-regulatory networks affect osteosarcoma cell proliferation. PLoS Comput Biol 9:1-13.
28 Pujari R, Hunte R, Khan WN, Shembade N (2013) A20-mediated negative regulation of canonical NF-$\kappa$B signaling pathway. Immunol Res 57:166-171.   DOI
29 Rahman MM, McFadden G (2011) Modulation of NF-$\kappa$B signaling by microbial pathogens. Nat Rev Microbiol 9:291-306.   DOI   ScienceOn
30 Rieser E, Cordier SM, Walczak H (2013) Linear ubiquitination: a newly discovered regulator of cell signaling. Trends Biochem Sci 38:94-102.   DOI   ScienceOn
31 Sakuda S, Tamura S, Yamada A, Miyagawa J, Yamamoto K, Kiso S, Ito N, Higashiyama S, Taniguchi N, Kawata S, Matsuzawa Y (2002) NF-kappaB activation in nonparenchymal liver cells after partial hepatectomy in rats: possible involvement in expression of heparinbinding epidermal growth factor-like growth factor. J Hepatol 36:527-533.   DOI   ScienceOn
32 Smida J, Baumhoer D, Rosemann M, Walch A, Bielack S, Poremba C, Remberger K, Korsching E, Scheurlen W, Dierkes C, Burdach S, Jundt G, Atkinson MJ, Nathrath M (2010) Genomic alterations and allelic imbalances are strong prognostic predictors in Osteosarcoma. Clin Cancer Res 16:4256-4267.   DOI
33 Sakurai T, Maeda S, Chang L, Karin M (2006) Loss of hepatic NF-kappa B activity enhances chemical heaptocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation. Proc Natl Acad Sci USA 103: 10544-10551.   DOI   ScienceOn
34 Shimada M (2013) MicroRNA-mediated regulation of apoptosis in osteosarcoma. J Carcinogene Mutagene S6:1-4.
35 Silverman N, Maniatis T (2001) NF-$\kappa$B signaling pathways in mammalian and insect innate immunity. Genes Dev 15:2321-2342.   DOI   ScienceOn
36 Solt LA, Madge LA, Orange JS, May MJ (2007) Interleukin-1-induced NF-$\kappa$B activation is NEMO-dependent but does not require IKK. J Biol Chem 282:8724-8733.   DOI   ScienceOn
37 Song L, Yang J, Duan P, Xu J, Luo X, Luo F, Zhang Z, Hou T, Liu B, Zhou Q (2013) MicroRNA-24 inhibits osteosarcoma cell proliferation both in vitro and in vivo by targeting LPAATb. Arch Biochem Biophys 535: 128-135.   DOI   ScienceOn
38 Stiller CA (2007) International patterns of cancer incidence in adolescents. Cancer Treat Rev 33:631-645.   DOI   ScienceOn
39 Sun B, Karin M (2008) NF-$\kappa$B signaling, liver disease and hepatoprotective agents. Oncogene 27:6228-6244.   DOI   ScienceOn
40 Sun SC (2011) Non-canonical NF-$\kappa$B signaling pathway. Cell Research 21:71-85.   DOI   ScienceOn
41 Tan G, Niu J, Shi Y, Ouyang H, Wu ZH (2012) NF-$\kappa$B dependent microRNA-125b upregulation promotes cell survival by targeting p38$\alpha$ upon UV radiation. J Biol Chem 287:33036-33047.   DOI
42 Vallabhapurapu S, Karin M (2009) Regulation and function of NF-$\kappa$B transcription factors in the immune system. Annu Rev Immunol 27:693-733.   DOI   ScienceOn
43 Tang QL, Xie XB, Wang J, Chen Q, Han AJ, Zou CY, Yin JQ, Liu DW, Liang Y, Zhao ZQ, Yong BC, Zhang RH, Feng QS, Deng WG, Zhu XF, Zhou BP, Zeng YX, Shen JN, Kang T (2012) Glycogen synthase Kinase-3$\beta$, NF-$\kappa$B signaling and tumorigenesis of human osteosarcoma. J Natl Cancer Inst 104:1-15.
44 Thayanithy V, Sarver AL, Kartha RV, Li L, Angstadt AY, Breen M, Steer CJ, Modiano JF, Subramanian S (2012) Perturbation of 14q32 miRNAs-cMYC gene network in osteosarcoma. Bone 50:171-181.   DOI   ScienceOn
45 Uwe S (2008) Anti-inflammatory interventions of NF-$\kappa$B signaling: Potential applications and risks. Biochem Pharmacol 75:1567-1579.   DOI   ScienceOn
46 Vigorita VJ (2008) Orthopaedic Pathology. Lippincott, Williams & Wilkins, Philadelphia, PA, USA.
47 Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS (1998) NF-$\kappa$B antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281:1680-1683.   DOI   ScienceOn
48 Won KY, Kim YW, Kim HS, Lee SK, Jung WW, Park YK (2013) MicroRNA-199b-5p is involved in the Notch signaling pathway in osteosarcoma. Hum Pathol 44: 1648-1655.   DOI   ScienceOn
49 Wu CJ, Conze DB, Li T, Srinivasula SM, Ashwell JD (2006) Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation. Nat Cell Biol 8:398-406.   DOI   ScienceOn
50 Wu X, Zhong D, Gao Q, Zhai W, Ding Z, Wu J (2013) MicroRNA-34a inhibits fuman osteosarcoma proliferation by downregulating ether a go-go 1 expression. Int J Med Sci 10:676-682.   DOI
51 Xia JT, Chen LZ, Jian WH, Wang KB, Yang YZ, He WL, He YL, Chen D, Li W (2014) MicroRNA-362 induces cell proliferation and apoptosis resistance in gastric cancer by activation of NF-$\kappa$B signaling. J Transl Med 12:1-12.   DOI   ScienceOn
52 Zhang L, Ding X, Cui J, Xu H, Chen J, Gong YN, Hu L, Zhou Y, Ge J, Lu Q, Liu L, Chen S, Shao F (2012) Cysteine methylation disrupts ubiquitin-chain sensing in NF-$\kappa$B activation. Nature 481:204-208.
53 Yin JQ, Wen L, Wu LC, Gao ZH, Huang G, Wang J, Zou CY, Tan PX, Yong BC, Jia Q, Shen JN (2013) The glycogen synthase kinase-3$\beta$/nuclear factor-kappa B pathway is involved in cinobufagin-induced apoptosis in cultured osteosarcoma cells. Toxicol Lett 218:129-136.   DOI   ScienceOn
54 Zhang C, Yao C, Haopeng L, Wang G, Xijng H (2014) Combined elevation of microRNA-196a and microRNA-196b in sera predicts unfavorable prognosis in patients with OSs. Int J Mol Sci 15:6544-6555.   DOI
55 Zhang H, Cai X, Wang Y, Tang H, Tong D, Ji F (2010) MicroRNA-143, down-regulated in Osteosarcoma, promotes apoptosis and suppresses tumorigenicity by targeting Bcl-2. Oncol Rep 24:1363-1369.
56 Zhao H, Li M, Li L, Yang X, Lan G, Zhang Y (2013) MiR-133b Is down-regulated in human OS and inhibits osteosarocma cells proliferation, migration and invasion, and promotes apoptosis. PLoS One 8:e83571.   DOI
57 Zhao N, Wang R, Zhou L, Zhu Y, Gong J, Zhuang SM (2014) MicroRNA-26b suppresses the NF-$\kappa$B signaling and enhances the chemosensitivity of hepatocellular carcinoma cells by targeting TAK1 and TAB3. Mol Cancer 13:1-11.   DOI   ScienceOn
58 Zhou G, Shi X, Zhang J, Wu S, Zhao J (2013) MicroRNAs in Osteosarcoma: From biological players to clinical contributors, a review. J Int Med Res 41:1-12.   DOI   ScienceOn
59 Zhou Y, Huang Z, Wu S, Zang X, Liu M, Shi J (2014) MiR-33a is up-regulated in chemoresistant osteosarcoma and promotes osteosarcoma cell resistance to cisplatin by down-regulating TWIST. J Exp Clin Cancer Res 33:12.   DOI   ScienceOn
60 Ziyan W, Shuhua Y, Xiufang W, Xiaoyun L (2011) Micro RNA-21 is involved in osteosarcoma cell invasion and migration. Med Oncol 28:1469-1474.   DOI   ScienceOn
61 Broadhead ML, Clark JCM, Myers DE, Dass CR, Choong PFM (2011) The molecular pathogenesis of osteosarcoma: A review. Sarcoma 2011:1-12.
62 Abbott DW, Wilkins A, Asara JM, Cantley LC (2004) The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO. Curr Biol 14:2217-2227.   DOI   ScienceOn
63 American Cancer Society OS: Overview (2013) Available: http://www.cancer.org/acs/groups/cid/documents/webcontent/003069-pdf
64 Baker RG, Hayden MS, Ghosh S (2011) NF-$\kappa$B, Inflammation, and metabolic disease. Cell Metab 13:11-22.   DOI   ScienceOn
65 Baritaki S, Bonavida, B (2010) Viral infection and cancer: the NF-kappaB/Snail/RKIP loop regulates target cell sensitivity to apoptosis by cytotoxic lymphocytes. Crit Rev Immunol 30:31-46.   DOI
66 Beristain AG, Narala SR, Di Grappa MA, Khokha R (2012) Homotypic RANK signaling differentially regulates proliferation, motility and cell survival in osteosarcoma and mammary epithelial cells. J Cell Sci 125:943-955.   DOI   ScienceOn
67 Chen F (2005) Is NF-$\kappa$B a culprit in type 2 diabetes? Biochem Biophys Res Commun 332:1-3.   DOI   ScienceOn
68 Chen L, Wang Q, Wang GD, Wang HS, Huang Y, Liu XM, Cai XH (2013) MiR-16 inhibits cell proliferation by targeting IGF1R and the Raf1-MEK1/2-ERK1/2 pathway in osteosarcoma. FEBS Lett 587:1366-1372.   DOI   ScienceOn
69 Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18: 997-1006.   DOI   ScienceOn
70 Davis BN, Hata A (2009) Regulation of MicroRNA Biogenesis: A miRiad of mechanisms. Cell Commun Signal 7:1-22.   DOI   ScienceOn
71 Duan Z, Choy E, Harmon D, Liu X, Susa M, Mankin H, Hornicek F (2011) MicroRNA-199a-3p is down regulated in human osteosarcoma and regulates cell proliferation and migration. Mol Cancer Ther 10:1337-1345.   DOI
72 Esquela-Kerscher A, Slack FJ (2006) Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer (4):259-269.
73 Ghosh S, Karin M (2002) Missing pieces in the NFkappaB puzzle. Cell 109:S81-96.   DOI   ScienceOn
74 Fan L, Wu Q, Xing X, Wei Y, Shao Z (2012) MicroRNA-145 targets vascular endothelial growth factor and inhibits invasion and metastasis of osteosarcoma cells. Acta Biochim Biophys Sin (Shanghai) 44:407-414.   DOI   ScienceOn
75 Felx M, Guyot MC, Isler M, Turcotte RE, Doyon J, Khatib AM, Leclerc S, Moreau A, Moldovan F (2006) Endothelin-1 (ET-1) promotes MMP-2 and MMP-9 induction involving the transcription factor NF-$\kappa$B in human Osteosarcoma. Clin Sci (Lond) 110:645-654.   DOI   ScienceOn
76 Geng S, Zhang X, Chen J, Liu X, Zhang H, Xu X, Ma Y, Li B, Zhang Y, Bi Z, Yang C (2014) The tumor supperssor role of miR-124 in osteosarcoma. PLos one 9: e91566.   DOI   ScienceOn
77 Hayden MS, Ghosh S (2008) Shared principles in NF-$\kappa$B signaling. Cell 132:344-362.   DOI   ScienceOn
78 He C, Xiong J, Xu X, Lu W, Liu L, Xiao D, Wang D (2009) Functional elucidation of MiR-34 in osteosarcoma cells and primary tumor samples. Biochem Biophys Res Commun 388:35-40.   DOI   ScienceOn
79 Hoesel B, Schmid JA (2013) The complexity of NF-$\kappa$B signaling in inflammation and cancer. Mol Cancer 12: 1-15.   DOI
80 Huxford T, Ghosh G (2009) A structural guide to proteins of the NF-kappaB signaling module. Cold Spring Harb Perspect Biol 1:1-16.
81 Iliopoulos D, Hirsch HA, Struhl K (2009) An epigenetic switch involving NF-$\kappa$B, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139: 693-706.   DOI   ScienceOn
82 Jin J, Cai L, Liu ZM, Zhou XS (2013) MiRNA-218 inhibits OS cell migration and invasion by downregulating of TIAM1, MMP2 and MMP9. Asian Pac J Cancer Prev 14:3681-3684.   DOI   ScienceOn
83 Kaltschmidt B, Kaltschmidt C (2009) NF-$\kappa$B in the nervous system. Cold Spring Harb Perspect Biol 1:1-13.