Title : Mechanistic Basis of Arsenic Induced Carcinogenesis: Differential miRNA Expression

Vol 6 No 2 (2023): Volume 06 Issue 02 February 2023

Article Date Published : 24 February 2023 | Page No.: 1599-1617 | Google Scholar | Crossref doi for this article

Abstract :

Arsenic, a toxic metalloid, provokes many detrimental consequences to human health. It is prevalent in earth’s crust and poses a major threat to humans globally. Inorganic arsenic exposure occurs mainly via drinking water or food and is metabolized in mammals to form organic metabolites/ end products. Chronic exposure to arsenic causes lung, skin and urinary bladder cancers and increases the risks of liver, kidney and prostate cancers. Arsenic-induced ROS generation, disturbances in several signaling pathways, DNA repair inhibition, chromosomal aberrations, and epigenetic changes including alterations in DNA methylation, histone modifications and differential miRNA expression profiles are involved in cancer progression, and malignant transformation. However, details of arsenic-induced carcinogenesis and molecular mechanisms involved are still remaining obscure. MicroRNAs are post-transcriptional gene expression regulators and themselves may act as oncogenes and tumor suppressor genes. Differential miRNA expression is implicated in several human cancers. This review covers general mechanistic basis of arsenic-induced carcinogenesis, explores recent in-vitro, in-vivo and cohort studies on differential miRNA expression profiles and shares associated molecular mechanistic data on miRNA dysregulation and their functional consequences leading to arsenic induced tumorigenesis, metastasis and cancer, also discusses the future directions.

Keywords :

Arsenic, carcinogenesis, in-vitro and in-vivo studies., miRNA dysregulation, molecular mechanisms

References :

  1. Al-Eryani L, Jenkins SF, States VA, et al (2018a) MiRNA expression profiles of premalignant and malignant arsenic-induced skin lesions. PLoS One 13:1–13. https://doi.org/10.1371/journal.pone.0202579
  2. Al-Eryani L, Waigel S, Tyagi A, et al (2018b) Differentially expressed mRNA targets of differentially expressed miRNAs predict changes in the TP53 axis and carcinogenesis-related pathways in human keratinocytes chronically exposed to arsenic. Toxicol Sci 162:645–654. https://doi.org/10.1093/toxsci/kfx292
  3. Bailey KA, Fry RC (2014) Arsenic-Associated Changes to the Epigenome: What Are the Functional Consequences? Curr Environ Heal Reports 1:22–34. https://doi.org/10.1007/s40572-013-0002-8
  4. Banerjee M, Ferragut Cardoso A, Al-Eryani L, et al (2021) Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer. Arch Toxicol 95:2351–2365. https://doi.org/10.1007/s00204-021-03084-2
  5. Banerjee N, Bandyopadhyay AK, Dutta S, et al (2017) Increased microRNA 21 expression contributes to arsenic induced skin lesions, skin cancers and respiratory distress in chronically exposed individuals. Toxicology 378:10–16. https://doi.org/10.1016/j.tox.2017.01.006
  6. Banerjee N, Das S, Tripathy S, et al (2019) MicroRNAs play an important role in contributing to arsenic susceptibility in the chronically exposed individuals of West Bengal, India. Environ Sci Pollut Res 26:28052–28061. https://doi.org/10.1007/s11356-019-05980-8
  7. Beck R, Bommarito P, Douillet C, et al (2018) Circulating miRNAs Associated with Arsenic Exposure. Environ Sci Technol 52:14487–14495. https://doi.org/10.1021/acs.est.8b06457
  8. Bhattacharjee P, Banerjee M, Giri AK (2013) Role of genomic instability in arsenic-induced carcinogenicity. A review. Environ Int 53:29–40. https://doi.org/10.1016/j.envint.2012.12.004
  9. Bjørklund G, Aaseth J, Chirumbolo S, et al (2018) Effects of arsenic toxicity beyond epigenetic modifications. Environ Geochem Health 40:955–965. https://doi.org/10.1007/s10653-017-9967-9
  10. Burns FJ, Uddin AN, Wu F, et al (2004) Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: A dose-response study. Environ Health Perspect 112:599–603. https://doi.org/10.1289/ehp.6655
  11. Bushati N, Cohen SM (2007) microRNA Functions. Annu Rev Cell Dev Biol 23:175–205. https://doi.org/10.1146/annurev.cellbio.23.090506.123406
  12. Cai X, Yu Y, Huang Y, et al (2003) Arsenic trioxide-induced mitotic arrest and apoptosis in acute promyelocytic leukemia cells. Leukemia 17:1333–1337. https://doi.org/10.1038/sj.leu.2402983
  13. Calin GA, Dumitru CD, Shimizu M, et al (2002) Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99:15524–15529. https://doi.org/10.1073/pnas.242606799
  14. Cardoso APF, Al-Eryani L, Christopher States J (2018) Arsenic-Induced Carcinogenesis: The Impact of miRNA Dysregulation. Toxicol Sci 165:284–290. https://doi.org/10.1093/toxsci/kfy128
  15. Chen C, Jiang X, Gu S, Zhang Z (2017) MicroRNA-155 regulates arsenite-induced malignant transformation by targeting Nrf2-mediated oxidative damage in human bronchial epithelial cells. Toxicol Lett 278:38–47. https://doi.org/10.1016/j.toxlet.2017.07.215
  16. Chen C, Yang Q, Wang D, et al (2018a) MicroRNA-191, regulated by HIF-2α is involved in EMT and acquisition of a stem cell-like phenotype in arsenite-transformed human liver epithelial cells. Toxicol Vitr 48:128–136. https://doi.org/10.1016/j.tiv.2017.12.016
  17. Chen CC, Cheng YY, Chen SC, et al (2012) Cyclooxygenase-2 expression is up-regulated by 2-aminobiphenyl in a ROS and MAPK-dependent signaling pathway in a bladder cancer cell line. Chem Res Toxicol 25:695–705. https://doi.org/10.1021/tx2004689
  18. Chen QY, Li J, Sun H, et al (2018b) Role of miR-31 and SATB2 in arsenic-induced malignant BEAS-2B cell transformation. Mol Carcinog 57:968–977. https://doi.org/10.1002/mc.22817
  19. Duggal V, Rani A, Mehra R (2012) Assessment of arsenic content in groundwater samples collected from four districts of Northern Rajasthan, India Vikas. Der Chem Sin 3:1500–1504
  20. Fang X, Sun R, Hu Y, et al (2018) miRNA-182-5p, via HIF2α, contributes to arsenic carcinogenesis: evidence from human renal epithelial cells. Metallomics 10:1607–1617. https://doi.org/10.1039/c8mt00251g
  21. Friedman RC, Farh KKH, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105. https://doi.org/10.1101/gr.082701.108
  22. Gao S meng, Chen C, Wu J, et al (2010) Synergistic apoptosis induction in leukemic cells by miR-15a/16-1 and arsenic trioxide. Biochem Biophys Res Commun 403:203–208. https://doi.org/10.1016/j.bbrc.2010.10.137
  23. Ghosh N, Singh R (2009) Groundwater arsenic contamination in India: vulnerability and scope for remedy. Natl Inst Hydrol Uttarakhand 1–24
  24. Gonzalez H, Lema C, Kirken R, et al (2015) Arsenic-exposed Keratinocytes Exhibit Differential microRNAs Expression Profile; Potential Implication of miR-21, miR-200a and miR-141 in Melanoma Pathway. Clin Cancer Drugs 2:138–147. https://doi.org/10.2174/2212697×02666150629174704
  25. Ha M, Kim VN (2014) Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 15:509–524. https://doi.org/10.1038/nrm3838
  26. Hausser J, Zavolan M (2014) Identification and consequences of miRNA-target interactions-beyond repression of gene expression. Nat Rev Genet 15:599–612. https://doi.org/10.1038/nrg3765
  27. Hayes J, Peruzzi PP, Lawler S (2014) MicroRNAs in cancer: Biomarkers, functions and therapy. Trends Mol Med 20:460–469. https://doi.org/10.1016/j.molmed.2014.06.005
  28. He J, Wang M, Jiang Y, et al (2014) Chronic arsenic exposure and angiogenesis in human bronchial epithelial Cells via the ROS/miR-199a-5p/HIF-1α/COX-2 pathway. Environ Health Perspect 122:255–261. https://doi.org/10.1289/ehp.1307545
  29. He J, Xu Q, Jing Y, et al (2012) Reactive oxygen species regulate ERBB2 and ERBB3 expression via miR-199a/125b and DNA methylation. EMBO Rep 13:1116–1122. https://doi.org/10.1038/embor.2012.162
  30. Hu W, Chan CS, Wu R, et al (2010) Negative Regulation of Tumor Suppressor p53 by MicroRNA miR-504. Mol Cell 38:689–699. https://doi.org/10.1016/j.molcel.2010.05.027
  31. Huang Y, Zhang J, McHenry KT, et al (2008) Induction of cytoplasmic accumulation of p53: A mechanism for low levels of arsenic exposure to predispose cells for malignant transformation. Cancer Res 68:9131–9136. https://doi.org/10.1158/0008-5472.CAN-08-3025
  32. Humphries B, Wang Z, Yang C (2016) The role of microRNAs in metal carcinogen-induced cell malignant transformation and tumorigenesis. Food Chem Toxicol 98:58–65. https://doi.org/10.1016/j.fct.2016.02.012
  33. Hunt KM, Srivastava RK, Elmets CA, Athar M (2014) The mechanistic basis of arsenicosis: Pathogenesis of skin cancer. Cancer Lett. 211–219
  34. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2012) Arsenic, metals, fibres, and dusts. A Review of human carcinogens
  35. Jiang R, Li Y, Zhang A, et al (2014) The acquisition of cancer stem cell-like properties and neoplastic transformation of human keratinocytes induced by arsenite involves epigenetic silencing of let-7c via Ras/NF-κB. Toxicol Lett 227:91–98. https://doi.org/10.1016/j.toxlet.2014.03.020
  36. Karagas MR, Gossai A, Pierce B, Ahsan H (2015) Drinking Water Arsenic Contamination, Skin Lesions, and Malignancies: A Systematic Review of the Global Evidence. Curr Environ Heal reports 2:52–68. https://doi.org/10.1007/s40572-014-0040-x
  37. Kaur G, Dufour JM (2012) Cell lines: Valuable tools or useless artifacts. Spermatogenesis 2:1–5. https://doi.org/10.4161/spmg.19885
  38. Lee RC, L FR, Ambros V (1993) The C. elegans Heterochronic Gene lin-4 Encodes Small RNAs with Antisense Complementarity to lin-14. Cell 75:843–854
  39. Li L, Chen F (2016) Oxidative stress, epigenetics, and cancer stem cells in arsenic carcinogenesis and prevention I. Arsenic in environmental and occupational settings. Curr Pharmacol Rep April:2(2):57-63. https://doi.org/10.1007/s40495-016-0049-y
  40. Li Y, Kowdley K V. (2012) MicroRNAs in Common Human Diseases. Genomics, Proteomics Bioinforma 10:246–253. https://doi.org/10.1016/j.gpb.2012.07.005
  41. Li Y, Zhu X, Gu J, et al (2010) Anti-miR-21 oligonucleotide sensitizes leukemic K562 cells to arsenic trioxide by inducing apoptosis. Cancer Sci 101:948–954. https://doi.org/10.1111/j.1349-7006.2010.01489.x
  42. Ling M, Li Y, Xu Y, et al (2012) Regulation of miRNA-21 by reactive oxygen species-activated ERK/NF-κB in arsenite-induced cell transformation. Free Radic Biol Med 52:1508–1518. https://doi.org/10.1016/j.freeradbiomed.2012.02.020
  43. Liu J, Gunewardena S, Yue Cui J, et al (2020) Transplacental arsenic exposure produced 5-methylcytosine methylation changes and aberrant microRNA expressions in livers of male fetal mice. Toxicology 435:152409. https://doi.org/10.1016/j.tox.2020.152409
  44. LIU JQ, NIU Q, HU YH, et al (2018) The Bidirectional Effects of Arsenic on miRNA-21: A Systematic Review and Meta-analysis. Biomed Environ Sci 31:654–666. https://doi.org/10.3967/bes2018.090
  45. Liu X, Luo F, Ling M, et al (2016) MicroRNA-21 activation of ERK signaling via PTEN is involved in arsenite-induced autophagy in human hepatic L-02 cells. Toxicol Lett 252:1–10. https://doi.org/10.1016/j.toxlet.2016.04.015
  46. Lotterman CD, Kent OA, Mendell JT (2008) Functional integration of microRNAs into oncogenic and tumor suppressor pathways. Cell Cycle 7:2493–2499. https://doi.org/10.4161/cc.7.16.6452
  47. Luo F, Ji J, Liu Y, et al (2015) MicroRNA-21, up-regulated by arsenite, directs the epithelial-mesenchymal transition and enhances the invasive potential of transformed human bronchial epithelial cells by targeting PDCD4. Toxicol Lett 232:301–309. https://doi.org/10.1016/j.toxlet.2014.11.001
  48. Luo F, Xu Y, Ling M, et al (2013) Arsenite evokes IL-6 secretion, autocrine regulation of STAT3 signaling, and miR-21 expression, processes involved in the EMT and malignant transformation of human bronchial epithelial cells. Toxicol Appl Pharmacol 273:27–34. https://doi.org/10.1016/j.taap.2013.08.025
  49. MacFarlane L-A, R. Murphy P (2010) MicroRNA: Biogenesis, Function and Role in Cancer. Curr Genomics 11:537–561. https://doi.org/10.2174/138920210793175895
  50. Marsit CJ, Eddy K, Kelsey KT (2006) MicroRNA responses to cellular stress. Cancer Res 66:10843–10848. https://doi.org/10.1158/0008-5472.CAN-06-1894
  51. Martínez-Pacheco M, Hidalgo-Miranda A, Romero-Córdoba S, et al (2014) MRNA and miRNA expression patterns associated to pathways linked to metal mixture health effects. Gene 533:508–514. https://doi.org/10.1016/j.gene.2013.09.049
  52. Martinez VD, Vucic EA, Becker-Santos DD, et al (2011) Arsenic exposure and the induction of human cancers. J Toxicol 2011:. https://doi.org/10.1155/2011/431287
  53. Michailidi C, Hayashi M, Datta S, et al (2015) Involvement of epigenetics and EMT-related miRNA in arsenic-induced neoplastic transformation and their potential clinical use. Cancer Prev Res 8:208–221. https://doi.org/10.1158/1940-6207.CAPR-14-0251
  54. Nagpal N, Ahmad HM, Molparia B, Kulshreshtha R (2013) MicroRNA-191, an estrogen-responsive microRNA, functions as an oncogenic regulator in human breast cancer. Carcinogenesis 34:1889–1899. https://doi.org/10.1093/carcin/bgt107
  55. Ngalame NNO, Makia NL, Waalkes MP, Tokar EJ (2016) Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration. Toxicol Appl Pharmacol 312:11–18. https://doi.org/10.1016/j.taap.2015.12.013
  56. Ngalame NNO, Tokar EJ, Person RJ, et al (2014) Aberrant microRNA expression likely controls RAS oncogene activation during malignant transformation of human prostate epithelial and stem cells by arsenic. Toxicol Sci 138:268–277. https://doi.org/10.1093/toxsci/kfu002
  57. Peng Y, Croce CM (2016) The role of microRNAs in human cancer. Signal Transduct Target Ther 1:15004. https://doi.org/10.1038/sigtrans.2015.4
  58. Pratheeshkumar P, Son YO, Divya SP, et al (2016) Oncogenic transformation of human lung bronchial epithelial cells induced by arsenic involves ROS-dependent activation of STAT3-miR-21-PDCD4 mechanism. Sci Rep 6:37227. https://doi.org/10.1038/srep37227
  59. Rager JE, Bailey KA, Smeester L, et al (2014) Prenatal arsenic exposure and the epigenome: Altered microRNAs associated with innate and adaptive immune signaling in newborn cord blood. Environ Mol Mutagen 55:196–208. https://doi.org/10.1002/em.21842
  60. Reddy KB (2015) MicroRNA (miRNA) in cancer. Cancer Cell Int 15:4–9. https://doi.org/10.1186/s12935-015-0185-1
  61. Ren X, Gaile DP, Gong Z, et al (2015) Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress. Toxicol Appl Pharmacol 283:198–209. https://doi.org/10.1016/j.taap.2015.01.014
  62. Ren X, Mchale CM, Skibola CF, et al (2011) An emerging role for epigenetic dysregulation in arsenic toxicity and carcinogenesis. Environ Health Perspect 119:11–19. https://doi.org/10.1289/ehp.1002114
  63. Rojas E, Martínez-Pacheco M, Rodríguez-Sastre MA, Valverde M (2019) As-Cd-Pb Mixture Induces Cellular Transformation via Post-Transcriptional Regulation of Rad51c by miR-222. Cell Physiol Biochem 53:910–920. https://doi.org/10.33594/000000181
  64. Romero-Cordoba SL, Salido-Guadarrama I, Rodriguez-Dorantes M, Hidalgo-Miranda A (2014) miRNA biogenesis: Biological impact in the development of cancer. Cancer Biol Ther 15:1444–1455. https://doi.org/10.4161/15384047.2014.955442
  65. Rossman TG, Uddin AN, Burns FJ, Bosland MC (2001) Arsenite is a cocarcinogen with solar ultraviolet radiation for mouse skin: An animal model for arsenic carcinogenesis. Toxicol Appl Pharmacol 176:64–71. https://doi.org/10.1006/taap.2001.9277
  66. Ruíz-Vera T, Ochoa-Martínez ÁC, Zarazúa S, et al (2019) Circulating miRNA-126, -145 and -155 levels in Mexican women exposed to inorganic arsenic via drinking water. Environ Toxicol Pharmacol 67:79–86. https://doi.org/10.1016/j.etap.2019.02.004
  67. Sage AP, Minatel BC, Ng KW, et al (2017) Oncogenomic disruptions in arsenic-induced carcinogenesis. Oncotarget 8:25736–25755. https://doi.org/10.18632/oncotarget.15106
  68. Sampson VB, Rong NH, Han J, et al (2007) MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res 67:9762–9770. https://doi.org/10.1158/0008-5472.CAN-07-2462
  69. States JC (2015) Disruption of Mitotic Progression by Arsenic. Biol Trace Elem Res 166:34–40. https://doi.org/10.1007/s12011-015-0306-7
  70. Sturchio E, Colombo T, Boccia P, et al (2014) Arsenic exposure triggers a shift in microRNA expression. Sci Total Environ 472:672–680. https://doi.org/10.1016/j.scitotenv.2013.11.092
  71. Sun B, Xue J, Li J, et al (2017) Circulating miRNAs and their target genes associated with arsenism caused by coal-burning. Toxicol Res (Camb) 6:162–172. https://doi.org/10.1039/c6tx00428h
  72. Sun J, Yu M, Lu Y, et al (2014) Carcinogenic metalloid arsenic induces expression of mdig oncogene through JNK and STAT3 activation. Cancer Lett 346:257–263. https://doi.org/10.1016/j.canlet.2014.01.002
  73. Sun Y, Wang C, Wang L, et al (2018) Arsenic trioxide induces apoptosis and the formation of reactive oxygen species in rat glioma cells. Cell Mol Biol Lett 23:1–10. https://doi.org/10.1186/s11658-018-0074-4
  74. Taylor BF, McNeely SC, Miller HL, et al (2006) p53 suppression of arsenite-induced mitotic catastrophe is mediated by p21CIP1/WAF1. J Pharmacol Exp Ther 318:142–151. https://doi.org/10.1124/jpet.106.103077
  75. Wang M, Ge X, Zheng J, et al (2016) Role and mechanism of miR-222 in arsenic-transformed cells for inducing tumor growth. Oncotarget 7:17805–17814. https://doi.org/10.18632/oncotarget.7525
  76. Wang Z, Humphries B, Xiao H, et al (2014) MicroRNA-200b suppresses arsenic-transformed cell migration by targeting protein kinase Cα and wnt5b-protein kinase Cα positive feedback loop and inhibiting Rac1 activation. J Biol Chem 289:18373–18386. https://doi.org/10.1074/jbc.M114.554246
  77. Wang Z, Zhao Y, Smith E, et al (2011) Reversal and prevention of arsenic-induced human bronchial epithelial cell malignant transformation by microRNA-200b. Toxicol Sci 121:110–122. https://doi.org/10.1093/toxsci/kfr029
  78. Wei S, Xue J, Sun B, et al (2018) miR-145 via targeting ERCC2 is involved in arsenite-induced DNA damage in human hepatic cells. Elsevier Ireland Ltd
  79. Wellner U, Schubert J, Burk UC, et al (2009) The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol 11:1487–1495. https://doi.org/10.1038/ncb1998
  80. WHO (2001) ARSENIC AND ARSENIC COMPUNDS (Environmental Health Criteria 224), 2nd ed.
  81. WHO (2011) Guidelines for Drinking-water Quality 4th ed., WHO, Geneva, p. 340.
  82. Xu W, Luo F, Sun B, et al (2015) HIF-2α, acting via miR-191, is involved in angiogenesis and metastasis of arsenite-transformed HBE cells. Toxicol. Res. (Camb). 5:66–78
  83. Yamamura S, Saini S, Majid S, et al (2012) Microrna-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells. PLoS One 7:1–12. https://doi.org/10.1371/journal.pone.0029722
  84. Yang J, Chen Z, Wang X, et al (2017) Inactivation of miR-100 combined with arsenic treatment enhances the malignant transformation of BEAS-2B cells via stimulating epithelial -mesenchymal transition. Cancer Biol Ther 18:965–973. https://doi.org/10.1080/15384047.2017.1345393
  85. Yedjou C, Tchounwou P, Jenkins J, McMurray R (2010) Basic mechanisms of arsenic trioxide (ATO)-induced apoptosis in human leukemia (HL-60) cells. J Hematol Oncol 3:1–9. https://doi.org/10.1186/1756-8722-3-28
  86. Yu H, Liao W, Chai C (2006) Arsenic carcinogenesis in the skin. J Biomed Sci 13:657–666. https://doi.org/10.1007/s11373-006-9092-8
  87. Zeng Q, Zou Z, Wang Q, et al (2019) Association and risk of five miRNAs with arsenic-induced multiorgan damage. Sci Total Environ 680:1–9. https://doi.org/10.1016/j.scitotenv.2019.05.042
  88. Zhong M, Huang Z, Wang L, et al (2018) Malignant Transformation of Human Bronchial Epithelial Cells Induced by Arsenic through STAT3/miR-301a/SMAD4 Loop. Sci Rep 8:1–12. https://doi.org/10.1038/s41598-018-31516-0
  89. Zhou K, Liu M, Cao Y (2017a) New insight into microRNA functions in cancer: Oncogene-microRNA-tumor suppressor gene network. Front Mol Biosci 4:1–7. https://doi.org/10.3389/fmolb.2017.00046
  90. Zhou Y, Wang Y, Su J, et al (2017b) Integration of microRNAome, proteomics and metabolomics to analyze arsenic-induced malignant cell transformation. Oncotarget 8:90879–90896. https://doi.org/10.18632/oncotarget.18741

Author's Affiliation

   Placheril J. John
Professor, Department of Zoology, University of Rajasthan, Jaipur-302004 India

   Navneet Kumar
Centre for advanced studies, Department of Zoology, University of Rajasthan, Jaipur, India – 302004

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Placheril J. John, Navneet Kumar, 2023

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Mechanistic Basis of Arsenic Induced Carcinogenesis: Differential miRNA Expression. Placheril J. John, Navneet Kumar, 6(2), 1599-1617. Retrieved from https://ijcsrr.org/single-view/?id=9430&pid=8957

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