Therapeutic Potential of CRISPR/Cas9 Nuclear Scissors in the Modulation of microRNAs in Various Cancers: A Review


Cancer is leading cause of death around the world. There are many strategies have been planned to tackle the cancer progression but each has its own merits and demerits. The microRNA`s are controlling 60 percent human genome, have role in progressive timing, organogenesis, hematopoiesis, cell proliferation, apoptosis and possibly tumorgenesis by amplification or deletion of genes. There are many drugs like 5-fluorouracil (5-FU), Celecoxib and genistein were used to modulate the miRNA`s expression but their success rate remained least. The clustered regularly interspaced short palindromic repeat (CRISPR/ Cas9) is emerging technology used to modulate the expression of miR-17, miR-200c, and miR-141 with 96 percent success rate. This review will provide us information about the potential therapeutic use of CRISPR/Cas9 against defaulted microRNA`s in the longstanding repression and beginning or inhibition of cancer.


Neoplasms; MicroRNAs ;Therapeutic and CRISPR/ Cas9

Therapeutic Potential of CRISPR/Cas9 Nuclear Scissors in the Modulation of microRNAs in Various Cancers: A Review


Asra Iftakhar

E-mail: [email protected]
Affiliation: Institute of Pharmacy, Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan

Therapeutic Potential of CRISPR/Cas9 Nuclear Scissors in the Modulation of microRNAs in Various Cancers: A Review


1. Kim VN. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol. 2005;6(5):376-85. DOI: 10.1038/nrm1644 PMID: 15852042
2. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature. 2008;455(7209):58-63. DOI: 10.1038/nature07228 PMID: 18668040
3. Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15(8):509-24. DOI: 10.1038/nrm3838 PMID: 25027649
4. Yin Y, Shen C, Xie P, Cheng Z, Zhu Q. Construction of an initial microRNA regulation network in breast invasive carcinoma by bioinformatics analysis. Breast. 2016;26:1-10. DOI: 10.1016/j. breast.2015.11.008 PMID: 27017236
5. McCormick F. Cancer gene therapy: fringe or cutting edge? Nat Rev Cancer. 2001;1(2):130-41. DOI: 10.1038/35101008 PMID: 11905804
6. Roth JA. Adenovirus p53 gene therapy. Expert Opin Biol Ther. 2006;6(1):55-61. DOI: 10.1517/14712598.6.1.55 PMID: 16370914
7. Wiggins JF, Ruffino L, Kelnar K, Omotola M, Patrawala L, Brown D, et al. Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res. 2010;70(14):5923-30. DOI: 10.1158/0008-5472.CAN-10-0655 PMID: 20570894
8. Chiyomaru T, Yamamura S, Fukuhara S, Yoshino H, Kinoshita T, Majid S, et al. Genistein inhibits prostate cancer cell growth by targeting miR-34a and oncogenic HOTAIR. PLoS One. 2013;8(8):e70372. DOI: 10.1371/journal.pone.0070372 PMID: 23936419
9. Liu M, Zhang X, Hu CF, Xu Q, Zhu HX, Xu NZ. MicroRNA-mRNA functional pairs for cisplatin resistance in ovarian cancer cells. Chin J Cancer. 2014;33(6):285-94. DOI: 10.5732/cjc.013.10136 PMID: 24589211
10. Trang P, Wiggins JF, Daige CL, Cho C, Omotola M, Brown D, et al. Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol Ther. 2011;19(6):1116-22. DOI: 10.1038/mt.2011.48 PMID: 21427705
11. Peng J, Mo R, Ma J, Fan J. let-7b and let-7c are determinants of intrinsic chemoresistance in renal cell carcinoma. World J Surg Oncol. 2015;13(1):175. DOI: 10.1186/s12957-015-0596-4 PMID: 25951903
12. Saito Y, Suzuki H, Imaeda H, Matsuzaki J, Hirata K, Tsugawa H, et al. The tumor suppressor microRNA-29c is downregulated and restored by celecoxib in human gastric cancer cells. Int J Cancer. 2013;132(8):1751-60. DOI: 10.1002/ijc.27862 PMID: 23001726
13. Maresso KC, Tsai KY, Brown PH, Szabo E, Lippman S, Hawk ET. Molecular cancer prevention: Current status and future directions. CA Cancer J Clin. 2015;65(5):345-83. DOI: 10.3322/caac.21287 PMID: 26284997
14. Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science. 2010;327(5962):198-201. DOI: 10.1126/science.1178178 PMID: 19965718
15. Rupaimoole R, Han HD, Lopez-Berestein G, Sood AK. MicroRNA therapeutics: principles, expectations, and challenges. Chin J Cancer. 2011;30(6):368-70. DOI: 10.5732/cjc.011.10186 PMID: 21627858
16. Wu Y, Kang T. Protein stability regulators screening assay (Pro-SRSA): protein degradation meets the CRISPR-Cas9 library. Chin J Cancer. 2016;35(1):60. DOI: 10.1186/s40880-016-0125-z PMID: 27357860
17. Kawamura N, Nimura K, Nagano H, Yamaguchi S, Nonomura N, Kaneda Y. CRISPR/Cas9-mediated gene knockout of NANOG and NANOGP8 decreases the malignant potential of prostate cancer cells. Oncotarget. 2015;6(26):22361-74. DOI: 10.18632/oncotarget.4293 PMID: 26087476
18. Gaj T, Gersbach CA, Barbas CF, 3rd. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013;31(7):397-405. DOI: 10.1016/j.tibtech.2013.04.004 PMID: 23664777
19. Chang H, Yi B, Ma R, Zhang X, Zhao H, Xi Y. CRISPR/cas9, a novel genomic tool to knock down microRNA in vitro and in vivo. Sci Rep. 2016;6(1):22312. DOI: 10.1038/srep22312 PMID: 26924382
20. Bhaya D, Davison M, Barrangou R. CRISPR-Cas systems in bacteria and archaea: versatile small RNAs for adaptive defense and regulation. Annu Rev Genet. 2011;45(1):273-97. DOI: 10.1146/annurev-genet-110410-132430 PMID: 22060043
21. Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005;436(7051):740-4. DOI: 10.1038/nature03868 PMID: 15973356
22. Fukuda T, Yamagata K, Fujiyama S, Matsumoto T, Koshida I, Yoshimura K, et al. DEAD-box RNA helicase subunits of the DroAsra sha complex are required for processing of rRNA and a subset of microRNAs. Nat Cell Biol. 2007;9(5):604-11. DOI: 10.1038/ncb1577 PMID: 17435748
23. Havens MA, Reich AA, Hastings ML. Drosha promotes splicing of a pre-microRNA-like alternative exon. PLoS Genet. 2014;10(5):e1004312. DOI: 10.1371/journal.pgen.1004312 PMID: 24786770
24. Zeng Y, Cullen BR. Efficient processing of primary microRNA hairpins by Drosha requires flanking nonstructured RNA sequences. J Biol Chem. 2005;280(30):27595-603. DOI: 10.1074/jbc.M504714200 PMID: 15932881
25. 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):1068-77. DOI: 10.1261/rna.044537.114 PMID: 24854622
26. Kawahara H, Okada Y, Imai T, Iwanami A, Mischel PS, Okano H. Musashi1 cooperates in abnormal cell lineage protein 28 (Lin28)-mediated let-7 family microRNA biogenesis in early neural differentiation. J Biol Chem. 2011;286(18):16121-30. DOI: 10.1074/jbc.M110.199166 PMID: 21378162
27. Yu Z, Wang L, Wang C, Ju X, Wang M, Chen K, et al. Cyclin D1 induction of Dicer governs microRNA processing and expression in breast cancer. Nat Commun. 2013;4(1):2812. DOI: 10.1038/ncomms3812 PMID: 24287487
28. Ota H, Sakurai M, Gupta R, Valente L, Wulff BE, Ariyoshi K, et al. ADAR1 forms a complex with Dicer to promote microRNA processing and RNA-induced gene silencing. Cell. 2013;153(3):575-89. DOI: 10.1016/j.cell.2013.03.024 PMID: 23622242
29. Su X, Chakravarti D, Flores ER. p63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis. Nat Rev Cancer. 2013;13(2):136-43. DOI: 10.1038/nrc3446 PMID: 23344544
30. Wiesen JL, Tomasi TB. Dicer is regulated by cellular stresses and interferons. Mol Immunol. 2009;46(6):1222-8. DOI: 10.1016/j.molimm. 2008.11.012 PMID: 19118902
31. Miyoshi K, Okada TN, Siomi H, Siomi MC. Characterization of the miRNA-RISC loading complex and miRNA-RISC formed in the Drosophila miRNA pathway. RNA. 2009;15(7):1282-91. DOI: 10.1261/rna.1541209 PMID: 19451544
32. Martinez NJ, Chang HM, Borrajo Jde R, Gregory RI. The co-chaperones Fkbp4/5 control Argonaute2 expression and facilitate RISC assembly. RNA. 2013;19(11):1583-93. DOI: 10.1261/rna.040790.113 PMID: 24049110
33. Zhang J, Li S, Li L, Li M, Guo C, Yao J, et al. Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics Proteomics Bioinformatics. 2015;13(1):17-24. DOI: 10.1016/j.gpb.2015.02.001 PMID: 25724326
34. Pratt AJ, MacRae IJ. The RNA-induced silencing complex: a versatile gene-silencing machine. J Biol Chem. 2009;284(27):17897-901. DOI: 10.1074/jbc.R900012200 PMID: 19342379
35. Wang HW, Noland C, Siridechadilok B, Taylor DW, Ma E, Felderer K, et al. Structural insights into RNA processing by the human RISC-loading complex. Nat Struct Mol Biol. 2009;16(11):1148-53. DOI: 10.1038/nsmb.1673 PMID: 19820710
36. Fu Y, Sander JD, Reyon D, Cascio VM, Joung JK. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol. 2014;32(3):279-84. DOI: 10.1038/nbt.2808 PMID: 24463574
37. Slaymaker IM, Gao L, Zetsche B, Scott DA, Yan WX, Zhang F. Rationally engineered Cas9 nucleases with improved specificity. Science. 2016;351(6268):84-8. DOI: 10.1126/science.aad5227 PMID: 26628643
38. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819-23. DOI: 10.1126/science.1231143 PMID: 23287718
39. Barrangou R, Marraffini LA. CRISPR-Cas systems: Prokaryotes upgrade to adaptive immunity. Mol Cell. 2014;54(2):234-44. DOI: 10.1016/j.molcel.2014.03.011 PMID: 24766887
40. Zhang F, Wen Y, Guo X. CRISPR/Cas9 for genome editing: progress, implications and challenges. Hum Mol Genet. 2014;23(R1):R40-6. DOI: 10.1093/hmg/ddu125 PMID: 24651067
41. Yue J, Du Z, Zhou F-M, Dong P, Pfeffer LM. Applications of CRSIPR/Cas9 in Cancer Research. Cancer Med Anti Cancer Drugs. 2016;1(1):1000103.
42. Smurnyy Y, Cai M, Wu H, McWhinnie E, Tallarico JA, Yang Y, et al. DNA sequencing and CRISPR-Cas9 gene editing for target validation in mammalian cells. Nat Chem Biol. 2014;10(8):623-5. DOI: 10.1038/nchembio.1550 PMID: 24929529
43. Neggers JE, Vercruysse T, Jacquemyn M, Vanstreels E, Baloglu E, Shacham S, et al. Identifying drug-target selectivity of small-molecule CRM1/XPO1 inhibitors by CRISPR/Cas9 genome editing. Chem Biol. 2015;22(1):107-16. DOI: 10.1016/j.chembiol.2014.11.015 PMID: 25579209
44. Hendel A, Kildebeck EJ, Fine EJ, Clark J, Punjya N, Sebastiano V, et al. Quantifying genome-editing outcomes at endogenous loci with SMRT sequencing. Cell Rep. 2014;7(1):293-305. DOI: 10.1016/j.celrep.2014.02.040 PMID: 24685129
45. Mangone FR, Miracca EC, Feilotter HE, Mulligan LM, Nagai MA. ATM gene mutations in sporadic breast cancer patients from Brazil. Springerplus. 2015;4(1):23. DOI: 10.1186/s40064-015-0787-z PMID: 25625042
46. Demicco EG, Park MS, Araujo DM, Fox PS, Bassett RL, Pollock RE, et al. Solitary fibrous tumor: a clinicopathological study of 110 cases and proposed risk assessment model. Mod Pathol. 2012;25(9):1298-306. DOI: 10.1038/modpathol.2012.83 PMID: 22575866
47. Zhang P, Pollock RE. Epigenetic Regulators: New Therapeutic Targets for Soft Tissue Sarcoma. Cancer Cell Microenviron. 2014;1(4). DOI: 10.14800/ccm.191 PMID: 26078988
48. Heckl D, Kowalczyk MS, Yudovich D, Belizaire R, Puram RV, Mc- Conkey ME, et al. Generation of mouse models of myeloid malignancy with combinatorial genetic lesions using CRISPR-Cas9 genome editing. Nat Biotechnol. 2014;32(9):941-6. DOI: 10.1038/nbt.2951 PMID: 24952903
49. Drost J, van Jaarsveld RH, Ponsioen B, Zimberlin C, van Boxtel R, Buijs A, et al. Sequential cancer mutations in cultured human intestinal stem cells. Nature. 2015;521(7550):43-7. DOI: 10.1038/nature14415 PMID: 25924068
50. Mets E, Van Peer G, Van der Meulen J, Boice M, Taghon T, Goossens S, et al. MicroRNA-128-3p is a novel oncomiR targeting PHF6 in T-cell acute lymphoblastic leukemia. Haematologica. 2014;99(8):1326-33. DOI: 10.3324/haematol.2013.099515 PMID: 24895337
51. Zhao Y, Dai Z, Liang Y, Yin M, Ma K, He M, et al. Sequence-specific inhibition of microRNA via CRISPR/CRISPRi system. Sci Rep. 2014;4(1):3943. DOI: 10.1038/srep03943 PMID: 24487629
52. Jiang Q, Meng X, Meng L, Chang N, Xiong J, Cao H, et al. Small indels induced by CRISPR/Cas9 in the 5’ region of microRNA lead to its depletion and Drosha processing retardance. RNA Biol. 2014;11(10):1243-9. DOI: 10.1080/15476286.2014.996067 PMID: 25590615
53. Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56(11):1733-41. DOI: 10.1373/clinchem.2010.147405 PMID: 20847327
54. Neviani P, Fabbri M. Exosomic microRNAs in the Tumor Microenvironment. Front Med (Lausanne). 2015;2:47. DOI: 10.3389/fmed.2015.00047 PMID: 26258125
55. Yin J, Bai Z, Song J, Yang Y, Wang J, Han W, et al. Differential expression of serum miR-126, miR-141 and miR-21 as novel biomarkers for early detection of liver metastasis in colorectal cancer. Chin J Cancer Res. 2014;26(1):95-103. DOI: 10.3978/j.issn.1000-9604.2014.02.07 PMID: 24653631
56. Chai S, Ma S. Clinical implications of microRNAs in liver cancer stem cells. Chin J Cancer. 2013;32(8):419-26. DOI: 10.5732/cjc.013.10038 PMID: 23668930
57. Sun Y, Guo F, Bagnoli M, Xue FX, Sun BC, Shmulevich I, et al. Key nodes of a microRNA network associated with the integrated mesenchymal subtype of high-grade serous ovarian cancer. Chin J Cancer. 2015;34(1):28-40. DOI: 10.5732/cjc.014.10284 PMID: 25556616
58. Muljo SA, Ansel KM, Kanellopoulou C, Livingston DM, Rao A, Rajewsky K. Aberrant T cell differentiation in the absence of Dicer. J Exp Med. 2005;202(2):261-9. DOI: 10.1084/jem.20050678 PMID: 16009718
59. Curtale G, Citarella F, Carissimi C, Goldoni M, Carucci N, Fulci V, et al. An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes. Blood. 2010;115(2):265-73. DOI: 10.1182/blood-2009-06-225987 PMID: 19965651
60. Williams AE, Perry MM, Moschos SA, Larner-Svensson HM, Lindsay MA. Role of miRNA-146a in the regulation of the innate immune response and cancer. Biochem Soc Trans. 2008;36(Pt 6):1211-5. DOI: 10.1042/BST0361211 PMID: 19021527
61. 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 U S A. 2006;103(33):12481-6. DOI: 10.1073/pnas.0605298103 PMID: 16885212
62. Zhao B, Zou J, Wang H, Johannsen E, Peng CW, Quackenbush J, et al. Epstein-Barr virus exploits intrinsic B-lymphocyte transcription programs to achieve immortal cell growth. Proc Natl Acad Sci U S A. 2011;108(36):14902-7. DOI: 10.1073/pnas.1108892108 PMID: 21746931
63. Fukao T, Fukuda Y, Kiga K, Sharif J, Hino K, Enomoto Y, et al. An evolutionarily conserved mechanism for microRNA-223 expression revealed by microRNA gene profiling. Cell. 2007;129(3):617-31. DOI: 10.1016/j.cell.2007.02.048 PMID: 17482553
64. Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature. 2008;455(7209):64-71. DOI: 10.1038/nature07242 PMID: 18668037
65. Zhou X, Jeker LT, Fife BT, Zhu S, Anderson MS, McManus MT, et al. Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med. 2008;205(9):1983-91. DOI: 10.1084/jem.20080707 PMID: 18725525
66. Xiao C, Calado DP, Galler G, Thai TH, Patterson HC, Wang J, et al. MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell. 2007;131(1):146-59. DOI: 10.1016/j.cell.2007.07.021 PMID: 17923094
67. Ghisi M, Corradin A, Basso K, Frasson C, Serafin V, Mukherjee S, et al. Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150. Blood. 2011;117(26):7053-62. DOI: 10.1182/blood-2010-12-326629 PMID: 21551231
68. Watanabe A, Tagawa H, Yamashita J, Teshima K, Nara M, Iwamoto K, et al. The role of microRNA-150 as a tumor suppressor in malignant lymphoma. Leukemia. 2011;25(8):1324-34. DOI: 10.1038/leu.2011.81 PMID: 21502955
69. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215-33. DOI: 10.1016/j.cell.2009.01.002 PMID: 19167326
70. Jiang X, Huang H, Li Z, He C, Li Y, Chen P, et al. MiR-495 is a tumor-suppressor microRNA down-regulated in MLL-rearranged leukemia. Proc Natl Acad Sci U S A. 2012;109(47):19397-402. DOI: 10.1073/pnas.1217519109 PMID: 23132946
71. Li G, Song Y, Zhang Y, Wang H, Xie J. miR-34b Targets HSF1 to Suppress Cell Survival in Acute Myeloid Leukemia. Oncol Res. 2016;24(2):109-16. DOI: 10.3727/096504016X14611963142254 PMID: 27296951
72. Hou LK, Yu Y, Xie YG, Wang J, Mao JF, Zhang B, et al. miR-340 and ZEB1 negative feedback loop regulates TGF-beta- mediated breast cancer progression. Oncotarget. 2016;7(18):26016-26. DOI: 10.18632/oncotarget.8421 PMID: 27036021
73. Zenz T, Mohr J, Eldering E, Kater AP, Buhler A, Kienle D, et al. miR-34a as part of the resistance network in chronic lymphocytic leukemia. Blood. 2009;113(16):3801-8. DOI: 10.1182/blood-2008-08-172254 PMID: 18941118
74. Zauli G, Voltan R, di Iasio MG, Bosco R, Melloni E, Sana ME, et al. miR-34a induces the downregulation of both E2F1 and B-Myb oncogenes in leukemic cells. Clin Cancer Res. 2011;17(9):2712-24. DOI: 10.1158/1078-0432.CCR-10-3244 PMID: 21367750
75. Cimino D, De Pitta C, Orso F, Zampini M, Casara S, Penna E, et al. miR148b is a major coordinator of breast cancer progression in a relapse-associated microRNA signature by targeting ITGA5, ROCK1, PIK3CA, NRAS, and CSF1. FASEB J. 2013;27(3):1223-35. DOI: 10.1096/fj.12-214692 PMID: 23233531
76. Prokopi M, Kousparou CA, Epenetos AA. The Secret Role of microRNAs in Cancer Stem Cell Development and Potential Therapy: A Notch-Pathway Approach. Front Oncol. 2014;4:389. DOI: 10.3389/fonc.2014.00389 PMID: 25717438
77. Ma H, Pan JS, Jin LX, Wu J, Ren YD, Chen P, et al. MicroRNA-17~92 inhibits colorectal cancer progression by targeting angiogenesis. Cancer Lett. 2016;376(2):293-302. DOI: 10.1016/j.canlet.2016.04.011 PMID: 27080303
78. Lv XB, Jiao Y, Qing Y, Hu H, Cui X, Lin T, et al. miR-124 suppresses multiple steps of breast cancer metastasis by targeting a cohort of pro-metastatic genes in vitro. Chin J Cancer. 2011;30(12):821-30. DOI: 10.5732/cjc.011.10289 PMID: 22085528
79. Duhachek-Muggy S, Zolkiewska A. ADAM12-L is a direct target of the miR-29 and miR-200 families in breast cancer. BMC Cancer. 2015;15(1):93. DOI: 10.1186/s12885-015-1108-1 PMID: 25886595
80. Tsai MM, Huang HW, Wang CS, Lee KF, Tsai CY, Lu PH, et al. MicroRNA-26b inhibits tumor metastasis by targeting the KPNA2/c-jun pathway in human gastric cancer. Oncotarget. 2016;7(26):39511-26. DOI: 10.18632/oncotarget.8629 PMID: 27078844
81. Wang M, Zhao C, Shi H, Zhang B, Zhang L, Zhang X, et al. Deregulated microRNAs in gastric cancer tissue-derived mesenchymal stem cells: novel biomarkers and a mechanism for gastric cancer. Br J Cancer. 2014;110(5):1199-210. DOI: 10.1038/bjc.2014.14 PMID: 24473397
82. Tsukamoto Y, Nakada C, Noguchi T, Tanigawa M, Nguyen LT, Uchida T, et al. MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3zeta. Cancer Res. 2010;70(6):2339-49. DOI: 10.1158/0008-5472.CAN-09-2777 PMID: 20215506
83. Zhang Z, Li Z, Gao C, Chen P, Chen J, Liu W, et al. miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab Invest. 2008;88(12):1358-66. DOI: 10.1038/labinvest.2008.94 PMID: 18794849
84. Zhang BG, Li JF, Yu BQ, Zhu ZG, Liu BY, Yan M. microRNA-21 promotes tumor proliferation and invasion in gastric cancer by targeting PTEN. Oncol Rep. 2012;27(4):1019-26. DOI: 10.3892/or.2012.1645 PMID: 22267008
85. Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13(3):272-86. DOI: 10.1016/j.ccr.2008.02.013 PMID: 18328430
86. Tivnan A, Zhao J, Johns TG, Day BW, Stringer BW, Boyd AW, et al. The tumor suppressor microRNA, miR-124a, is regulated by epigenetic silencing and by the transcriptional factor, REST in glioblastoma. Tumour Biol. 2014;35(2):1459-65. DOI: 10.1007/s13277-013-1200-6 PMID: 24068568
87. Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL. MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-alpha-PU.1 pathway. Nat Med. 2011;17(1):64-70. DOI: 10.1038/nm.2266 PMID: 21131957
88. Das SK, Stadelmeyer E, Schauer S, Schwarz A, Strohmaier H, Claudel T, et al. Micro RNA-124a regulates lipolysis via adipose triglyceride lipase and comparative gene identification 58. Int J Mol Sci. 2015;16(4):8555-68. DOI: 10.3390/ijms16048555 PMID: 25894224
89. Fontana L, Fiori ME, Albini S, Cifaldi L, Giovinazzi S, Forloni M, et al. Antagomir-17-5p abolishes the growth of therapy-resistant neuroblastoma through p21 and BIM. PLoS One. 2008;3(5):e2236. DOI: 10.1371/journal.pone.0002236 PMID: 18493594
90. Ge YF, Sun J, Jin CJ, Cao BQ, Jiang ZF, Shao JF. AntagomiR-27a targets FOXO3a in glioblastoma and suppresses U87 cell growth in vitro and in vivo. Asian Pac J Cancer Prev. 2013;14(2):963-8. DOI: 10.7314/apjcp.2013.14.2.963 PMID: 23621269
91. Tang H, Liu X, Wang Z, She X, Zeng X, Deng M, et al. Interaction of hsa-miR-381 and glioma suppressor LRRC4 is involved in glioma growth. Brain Res. 2011;1390:21-32. DOI: 10.1016/j.brainres.2011.03.034 PMID: 21435336
92. Xia X, Li Y, Wang W, Tang F, Tan J, Sun L, et al. MicroRNA-1908 functions as a glioblastoma oncogene by suppressing PTEN tumor suppressor pathway. Mol Cancer. 2015;14(1):154. DOI: 10.1186/s12943-015-0423-0 PMID: 26265437
93. Bao Y, Chen Z, Guo Y, Feng Y, Li Z, Han W, et al. Tumor suppressor microRNA-27a in colorectal carcinogenesis and progression by targeting SGPP1 and Smad2. PLoS One. 2014;9(8):e105991. DOI: 10.1371/journal.pone.0105991 PMID: 25166914
94. Chiyomaru T, Yamamura S, Fukuhara S, Hidaka H, Majid S, Saini S, et al. Genistein up-regulates tumor suppressor microRNA-574-3p in prostate cancer. PLoS One. 2013;8(3):e58929. DOI: 10.1371/journal.pone.0058929 PMID: 23554959
95. Li J, Liang H, Bai M, Ning T, Wang C, Fan Q, et al. Correction: miR-135b Promotes Cancer Progression by Targeting Transforming Growth Factor Beta Receptor II (TGFBR2) in Colorectal Cancer. PLoS One. 2015;10(12):e0145589. DOI: 10.1371/journal. pone.0145589 PMID: 26677848
96. Ji D, Chen Z, Li M, Zhan T, Yao Y, Zhang Z, et al. MicroRNA-181a promotes tumor growth and liver metastasis in colorectal cancer by targeting the tumor suppressor WIF-1. Mol Cancer. 2014;13(1):86. DOI: 10.1186/1476-4598-13-86 PMID: 24755295
97. Tang B, Lei B, Qi G, Liang X, Tang F, Yuan S, et al. MicroRNA-155-3p promotes hepatocellular carcinoma formation by suppressing FBXW7 expression. J Exp Clin Cancer Res. 2016;35(1):93. DOI: 10.1186/s13046-016-0371-6 PMID: 27306418
98. Simerzin A, Zorde-Khvalevsky E, Rivkin M, Adar R, Zucman-Rossi J, Couchy G, et al. The liver-specific microRNA-122*, the complementary strand of microRNA-122, acts as a tumor suppressor by modulating the p53/mouse double minute 2 homolog circuitry. Hepatology. 2016;64(5):1623-36. DOI: 10.1002/hep.28679 PMID: 27302319
99. Hu M, Wang M, Lu H, Wang X, Fang X, Wang J, et al. Loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CDC28 protein kinase regulatory subunit 1B. Oncotarget. 2016;7(28):43419-31. DOI: 10.18632/oncotarget.9728 PMID: 27270326
100. Abdelrahman MM, Fawzy IO, Bassiouni AA, Gomaa AI, Esmat G, Waked I, et al. Enhancing NK cell cytotoxicity by miR-182 in hepatocellular carcinoma. Hum Immunol. 2016;77(8):667-73. DOI: 10.1016/j.humimm.2016.04.020 PMID: 27262453
101. Zhu SM, Chen CM, Jiang ZY, Yuan B, Ji M, Wu FH, et al. MicroRNA-185 inhibits cell proliferation and epithelial-mesenchymal transition in hepatocellular carcinoma by targeting Six2. Eur Rev Med Pharmacol Sci. 2016;20(9):1712-9. PMID: 27212161
102. Ruan T, He X, Yu J, Hang Z. MicroRNA-186 targets Yes-associated protein 1 to inhibit Hippo signaling and tumorigenesis in hepatocellular carcinoma. Oncol Lett. 2016;11(4):2941-5. DOI: 10.3892/ol.2016.4312 PMID: 27073580
103. Yao Q, Xu H, Zhang QQ, Zhou H, Qu LH. MicroRNA-21 promotes cell proliferation and down-regulates the expression of programmed cell death 4 (PDCD4) in HeLa cervical carcinoma cells. Biochem Biophys Res Commun. 2009;388(3):539-42. DOI: 10.1016/j.bbrc.2009.08.044 PMID: 19682430
104. Gomez-Gomez Y, Organista-Nava J, Ocadiz-Delgado R, Garcia-Villa E, Leyva-Vazquez MA, Illades-Aguiar B, et al. The expression of miR-21 and miR-143 is deregulated by the HPV16 E7 oncoprotein and 17beta-estradiol. Int J Oncol. 2016;49(2):549-58. DOI: 10.3892/ijo.2016.3575 PMID: 27278606
105. Song N, Liang B, Wang D. The function of MiR-21 expression differences and pathogenesis on familial and triple negative breast Cancer serum. Pak J Pharm Sci. 2016;29(2 Suppl):679-84. PMID: 27113307
106. Yao T, Lin Z. MiR-21 is involved in cervical squamous cell tumorigenesis and regulates CCL20. Biochim Biophys Acta. 2012;1822(2):248-60. DOI: 10.1016/j.bbadis.2011.09.018 PMID: 22001440
107. Deng Y, Xiong Y, Liu Y. miR-376c inhibits cervical cancer cell proliferation and invasion by targeting BMI1. Int J Exp Pathol. 2016;97(3):257-65. DOI: 10.1111/iep.12177 PMID: 27345009
108. Siddique HR, Saleem M. Role of BMI1, a stem cell factor, in cancer recurrence and chemoresistance: preclinical and clinical evidences. Stem Cells. 2012;30(3):372-8. DOI: 10.1002/stem.1035 PMID: 22252887
109. Zou D, Zhou Q, Wang D, Guan L, Yuan L, Li S. The Downregulation of MicroRNA-10b and its Role in Cervical Cancer. Oncol Res. 2016;24(2):99-108. DOI: 10.3727/096504016X14611963142173 PMID: 27296950
110. Wang X, Xia Y. microRNA-328 inhibits cervical cancer cell proliferation and tumorigenesis by targeting TCF7L2. Biochem Biophys Res Commun. 2016;475(2):169-75. DOI: 10.1016/j.bbrc.2016.05.066 PMID: 27181358
111. Li J, Xia W, Su X, Qin X, Chen Y, Li S, et al. Species-specific mutual regulation of p53 and miR-138 between human, rat and mouse. Sci Rep. 2016;6(1):26187. DOI: 10.1038/srep26187 PMID: 27183959
112. Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, et al. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol. 2008;9(4):405-14. DOI: 10.1038/ni1575 PMID: 18327259
113. Pandey AK, Zhang Y, Zhang S, Li Y, Tucker-Kellogg G, Yang H, et al. TIP60-miR-22 axis as a prognostic marker of breast cancer progression. Oncotarget. 2015;6(38):41290-306. DOI: 10.18632/oncotarget.5636 PMID: 26512777

Therapeutic Potential of CRISPR/Cas9 Nuclear Scissors in the Modulation of microRNAs in Various Cancers: A Review

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Iftakhar A. Therapeutic Potential of CRISPR/Cas9 Nuclear Scissors in the Modulation of microRNAs in Various Cancers: A Review. Focus on Sciences. 2106; 4(1):1-9


Iftakhar, A. (2106). Therapeutic Potential of CRISPR/Cas9 Nuclear Scissors in the Modulation of microRNAs in Various Cancers: A Review. Focus on Sciences, 4(1), 1-9.


Asra Iftakhar "Therapeutic Potential of CRISPR/Cas9 Nuclear Scissors in the Modulation of microRNAs in Various Cancers: A Review". Focus on Sciences 4, no. 1 (2106).

Therapeutic Potential of CRISPR/Cas9 Nuclear Scissors in the Modulation of microRNAs in Various Cancers: A Review

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