Thanh Thi Ngoc NGUYEN, Minh Thi Hong TRAN, Vy Thi Lan NGUYEN, Uyen Doan Phuong NGUYEN, Giang Dien Thanh NGUYEN, Luan Huu HUYNH, Hue Thi NGUYEN

Single nucleotide polymorphisms in microRNAs action as biomarkers for breast cancer

MicroRNAs (miRNAs) have been recently described as small noncoding RNAs that are involved in numerous crucialphysiological processes, such as cell cycles, differentiation, development, and metabolism. Thus, dysregulation of these moleculescould lead to several severe disorders, including breast cancer (BC). Ongoing investigations in malignant growth diagnostics havedistinguished miRNAs as promising disease biomarkers. As with any other mRNAs, single nucleotide polymorphisms (SNPs) in DNAsequence encoding for miRNA (miR-SNPs) indeed lead to potential changes in the function of miRNA. In this study, miR-SNPs locatedin different miRNA sequence regions, which have been associated with BC in different ways, and the potential mechanisms of how thesemiR-SNPs develop the risk of the disease were discussed.

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Alshatwi AA, Shafi G, Hasan TN, Syed NA, Al-Hazzani AA et al. (2012). Differential expression profile and genetic variants of microRNAs sequences in breast cancer patients. PLoS One 7 (2): e30049-e30055. doi: 10.1371/journal.pone.0030049.
Auyeung VC, Ulitsky I, McGeary SE, Bartel DP (2013). Beyond secondary structure: primary-sequence determinants license pri-miRNA hairpins for processing. Cell 152 (4): 844-858. doi: 10.1016/j.cell.2013.01.031.
Aviv A, Anderson JJ, Shay JW (2017). Mutations, cancer and the telomere length paradox. Trends Cancer 3 (4): 253-258. doi: 10.1016/j.trecan.2017.02.005.
Bansal C, Sharma KL, Misra S, Srivastava AN, Mittal B et al. (2014). Common genetic variants in pre-microRNAs and risk of breast cancer in the North Indian population. Ecancermedicalscience 8: 473. doi: 10.3332/ecancer.2014.473.
Bensen JT, Graff M, Young KL, Sethupathy P, Parker J et al. (2018). A survey of microRNA single nucleotide polymorphisms identifies novel breast cancer susceptibility loci in a casecontrol, population-based study of African-American women. Breast Cancer Res 20 (1): 45. doi: 10.1186/s13058-018-0964-4.
Cammaerts S, Strazisar M, De Rijk P, Del Favero J (2015). Genetic variants in microRNA genes: impact on microRNA expression, function, and disease. Frontiers in Genetics 6: 186-198. doi: 10.3389/fgene.2015.00186.
Catalanotto C, Cogoni C, Zardo G (2016). MicroRNA in control of gene expression: an overview of nuclear functions. International journal of molecular sciences 17 (10): 1712-1729. doi: 10.3390/ijms17101712.
Chacon-Cortes D, Smith RA, Haupt LM, Lea RA, Youl PH et al. (2015a). Genetic association analysis of miRNA SNPs implicates MIR145 in breast cancer susceptibility. BMC Medical Genetics 16 (1): 107-118. doi: 10.1186/s12881-015- 0248-0.
Chacon-Cortes D, Smith RA, Lea RA, Youl PH, Griffiths LR (2015b). Association of microRNA 17–92 cluster host gene (MIR17HG) polymorphisms with breast cancer. Tumor Biology 36 (7): 5369-5376. doi: 10.1007/s13277-015-3200-1.
Chen J, Qin Z, Jiang Y, Wang Y, He Y et al. (2014a). Genetic variations in the flanking regions of miR-101-2 are associated with increased risk of breast cancer. PLoS One 9 (1): e86319-e86324. doi: 10.1371/journal.pone.0086319.
Chen K, Song F, Calin GA, Wei Q, Hao X et al. (2008). Polymorphisms in microRNA targets: a gold mine for molecular epidemiology. Carcinogenesis 29 (7): 1306-1311. doi: 10.1093/carcin/bgn116.
Chen QH, Wang QB, Zhang B (2014b). Ethnicity modifies the association between functional microRNA polymorphisms and breast cancer risk: a HuGE meta-analysis. Tumour Biology 35 (1): 529-543. doi: 10.1007/s13277-013-1074-7.
Cheng Q, Chang JT, Geradts J, Neckers LM, Haystead T et al. (2012). Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer. Breast Cancer Research 14 (2): R62-R77. doi: 10.1186/bcr3168.
Cho WC, Chow AS, Au JS (2011). MiR-145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1. RNA Biology 8 (1): 125-131. doi: 10.4161/rna.8.1.14259.
Dai ZJ, Shao YP, Wang XJ, Xu D, Kang HF et al. (2015). Five common functional polymorphisms in microRNAs (rs2910164, rs2292832, rs11614913, rs3746444, rs895819) and the susceptibility to breast cancer: evidence from 8361 cancer cases and 8504 controls. Current Pharmaceutical Design 21 (11): 1455-1463. doi: 10.2174/1381612821666141208143533.
Deng CX (2006). BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution. Nucleic Acids Research 34 (5): 1416-1426. doi: 10.1093/nar/gkl010.
Duan X, Zhang D, Wang S, Feng X, Wang T et al. (2020). Effects of polycyclic aromatic hydrocarbon exposure and miRNA variations on peripheral blood leukocyte DNA telomere length: a cross-sectional study in Henan Province, China. Science of the Total Environment 703: 135600-135608. doi: 10.1016/j. scitotenv.2019.135600.
Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D et al. (2007). Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447 (7148): 1087-1093. doi: 10.1038/nature05887.
Feng X, Ji D, Liang C, Fan S (2019). Does miR-618 rs2682818 variant affect cancer susceptibility? Evidence from 10 case-control studies. Bioscience Reports 39 (8): BSR20190741. doi: 10.1042/ BSR20190741.
Fu A, Hoffman AE, Liu R, Jacobs DI, Zheng T et al. (2014). Targetome profiling and functional genetics implicate miR-618 in lymphomagenesis. Epigenetics 9 (5): 730-737. doi: 10.4161/ epi.27996.
Gu S, Jin L, Zhang Y, Huang Y, Zhang F et al. (2012). The loop position of shRNAs and pre-miRNAs is critical for the accuracy of dicer processing in vivo. Cell 151 (4): 900-911. doi: 10.1016/j. cell.2012.09.042.
Han J, Lee Y, Yeom K-H, Kim Y-K, Jin H et al. (2004). The DroshaDGCR8 complex in primary microRNA processing. Genes & Development 18 (24): 3016-3027. doi: 10.1101/gad.1262504.
Han J, Lee Y, Yeom KH, Nam JW, Heo I et al. (2006). Molecular basis for the recognition of primary microRNAs by the DroshaDGCR8 complex. Cell 125 (5): 887-901. doi: 10.1016/j. cell.2006.03.043.
Hashemi M, Sanaei S, Rezaei M, Bahari G, Hashemi SM et al. (2016). miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation. Experimental Oncology 38 (1): 57-59.
Hoffman AE, Zheng T, Yi C, Leaderer D, Weidhaas J et al. (2009). microRNA miR-196a-2 and breast cancer: a genetic and epigenetic association study and functional analysis. Cancer Research 69 (14): 5970-5977. doi: 10.1158/0008-5472.CAN09-0236.
Hu W, Coller J (2012). What comes first: translational repression or mRNA degradation? The deepening mystery of microRNA function. Cell Research 22 (9): 1322-1324. doi: 10.1038/ cr.2012.80.
Hu Z, Liang J, Wang Z, Tian T, Zhou X et al. (2009). Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Human Mutation 30 (1): 79-84. doi: 10.1002/humu.20837.
Huang AJ, Yu KD, Li J, Fan L, Shao ZM (2012). Polymorphism rs4919510: C>G in mature sequence of human microRNA-608 contributes to the risk of HER2-positive breast cancer but not other subtypes. PLoS One 7 (5): e35252-e35260. doi: 10.1371/ journal.pone.0035252.
Said BI, Malkin D (2015). A functional variant in miR-605 modifies the age of onset in Li-Fraumeni syndrome. Cancer Genetics 208 (1-2): 47-51. doi: 10.1016/j.cancergen.2014.12.003.
Iwakawa H-O, Tomari Y (2015). The functions of microRNAs: mRNA decay and translational repression. Trends in Cell Biology 25 (11): 651-665. doi: 10.1016/j.tcb.2015.07.011.
Jiao L, Zhang J, Dong Y, Duan B, Yu H et al. (2014). Association between miR-125a rs12976445 and survival in breast cancer patients. American Journal of Translational Research 6 (6): 869-875.
Kazemi A, Vallian S (2020). Significant association of miR-605 rs2043556 with susceptibility to breast cancer. Microrna 9 (2): 133-141. doi: 10.2174/2211536608666190926155149.
Kim VN (2004). MicroRNA precursors in motion: exportin-5 mediates their nuclear export. Trends in Cell Biology 14 (4): 156-159. doi: 10.1016/j.tcb.2004.02.006.
Kontorovich T, Levy A, Korostishevsky M, Nir U, Friedman E (2010). Single nucleotide polymorphisms in miRNA binding sites and miRNA genes as breast/ovarian cancer risk modifiers in Jewish high-risk women. International Journal of Cancer 127 (3): 589- 597. doi: 10.1002/ijc.25065.
Lehmann TP, Korski K, Ibbs M, Zawierucha P, Grodecka-Gazdecka S et al. (2013). rs12976445 variant in the pri-miR-125a correlates with a lower level of hsa-miR-125a and ERBB2 overexpression in breast cancer patients. Oncology Letters 5 (2): 569-573. doi: 10.3892/ol.2012.1040.
Lerner M, Lundgren J, Akhoondi S, Jahn A, Ng HF et al. (2011). MiRNA-27a controls FBW7/hCDC4-dependent cyclin E degradation and cell cycle progression. Cell Cycle 10 (13): 2172-2183. doi: 10.4161/cc.10.13.16248.
Li J-T, Jia L-T, Liu N-N, Zhu X-S, Liu Q-Q et al. (2015). MiRNA-101 inhibits breast cancer growth and metastasis by targeting CX chemokine receptor 7. Oncotarget 6 (31): 30818–30830. doi: 10.18632/oncotarget.5067.
Li X, Wang J, Jia Z, Cui Q, Zhang C et al. (2013). MiR-499 regulates cell proliferation and apoptosis during late-stage cardiac differentiation via Sox6 and cyclin D1. PLoS One 8 (9): e74504-e74518. doi: 10.1371/journal.pone.0074504.
Lian H, Wang L, Zhang J (2012). Increased risk of breast cancer associated with CC genotype of Has-miR-146a Rs2910164 polymorphism in Europeans. PLoS One 7 (2): e31615-e31622. doi: 10.1371/journal.pone.0031615.
Lin J, Huang S, Wu S, Ding J, Zhao Y et al. (2011). MicroRNA-423 promotes cell growth and regulates G(1)/S transition by targeting p21Cip1/Waf1 in hepatocellular carcinoma. Carcinogenesis 32 (11): 1641-1647. doi: 10.1093/carcin/ bgr199.
Ma L, Teruya-Feldstein J, Weinberg RA (2007). Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449 (7163): 682-688. doi: 10.1038/nature06174.
McNally EJ, Luncsford PJ, Armanios M (2019). Long telomeres and cancer risk: the price of cellular immortality. Journal of Clinical Investigation 130: 3474-3481. doi: 10.1172/JCI120851.
Minh TTH, Thanh NTN, Hue NT (2018). Association between selected microRNA SNPs and breast cancer risk in a Vietnamese population. International Journal of Human Genetics 18: 238- 246. doi: 10.31901/24566330.2018/18.3.658.
Mir R, Al Balawi IA, Duhier FMA (2018). Involvement of microRNA-423 gene variability in breast cancer progression in Saudi Arabia. Asian Pacific Journal of Cancer Prevention 19 (9): 2581-2589. doi: 10.22034/APJCP.2018.19.9.2581.
Morales S, De Mayo T, Gulppi FA, Gonzalez-Hormazabal P, Carrasco V et al. (2018). Genetic variants in pre-miR-146a, pre-miR-499, pre-miR-125a, pre-miR-605, and pri-miR-182 are associated with breast cancer susceptibility in a South American population. Genes 9 (9): 427-445. doi: 10.3390/genes9090427.
Morales S, Gulppi F, Gonzalez-Hormazabal P, Fernandez-Ramires R, Bravo T et al. (2016). Association of single nucleotide polymorphisms in pre-miR-27a, pre-miR-196a2, pre-miR-423, miR-608 and pre-miR-618 with breast cancer susceptibility in a South American population. BMC Genetics 17 (1): 109-119. doi: 10.1186/s12863-016-0415-0.
Nicoloso MS, Sun H, Spizzo R, Kim H, Wickramasinghe P et al. (2010). Single-nucleotide polymorphisms inside microRNA target sites influence tumor susceptibility. Cancer Research 70 (7): 2789-2798. doi: 10.1158/0008-5472.CAN-09-3541.
O’Brien J, Hayder H, Zayed Y, Peng C (2018). Overview of microRNA biogenesis, mechanisms of actions, and circulation. Frontiers in Endocrinology 9: 402-414. doi: 10.3389/fendo.2018.00402.
Qiu L-X, Wang Y, Xia Z-G, Xi B, Mao C et al. (2011). miR-196a2 C allele is a low-penetrant risk factor for cancer development. Cytokine 56 (3): 589-592. doi: 10.1016/j.cyto.2011.08.019.
Ryan BM (2017). microRNAs in cancer susceptibility. In: Croce CM and Fisher PB (editors). Advances in Cancer Research. Amsterdam, Netherlands: Elsevier, pp. 151-171.
Ryan BM, Robles AI, Harris CC (2010). Genetic variation in microRNA networks: the implications for cancer research. Nature Reviews Cancer 10 (6): 389-402. doi: 10.1038/nrc2867.
Schulman BRM, Esquela‐Kerscher A, Slack FJ (2005). Reciprocal expression of lin‐41 and the microRNAs let‐7 and mir‐125 during mouse embryogenesis. Developmental Dynamics: An Official Publication of the American Association of Anatomists 234 (4): 1046-1054. doi: 10.1002/dvdy.20599.
Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS et al. (2007). Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. Journal of Biological Chemistry 282 (2): 1479-1486. doi: 10.1074/jbc. M609383200.
Shastry BS (2009). SNPs: impact on gene function and phenotype. In: Komar AA (editors). Single Nucleotide Polymorphisms. Berlin, Germany: Springer, pp. 3-22.
Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB et al. (2008). A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis 29 (10): 1963-1966. doi: 10.1093/carcin/bgn172.
Smith RA, Jedlinski DJ, Gabrovska PN, Weinstein SR, Haupt L et al. (2012). A genetic variant located in miR-423 is associated with reduced breast cancer risk. Cancer Genomics & Proteomics 9 (3): 115-118.
Song Gao J, Zhang Y, Li M, Tucker LD, Machan JT et al. (2010). Atypical transcription of microRNA gene fragments. Nucleic Acids Research 38 (9): 2775-2787. doi: 10.1093/nar/gkp1242.
Stacey SN, Manolescu A, Sulem P, Rafnar T, Gudmundsson J et al. (2007). Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nature Genetics 39 (7): 865-869. doi: 10.1038/ng2064.
Starega-Roslan J, Krol J, Koscianska E, Kozlowski P, Szlachcic WJ et al. (2011). Structural basis of microRNA length variety. Nucleic Acids Research 39 (1): 257-268. doi: 10.1093/nar/gkq727.
Stoicea N, Du A, Lakis DC, Tipton C, Arias-Morales CE et al. (2016). The miRNA journey from theory to practice as a CNS biomarker. Frontiers in Genetics 7: 11. doi: 10.3389/ fgene.2016.00011.
Sun G, Yan J, Noltner K, Feng J, Li H et al. (2009). SNPs in human miRNA genes affect biogenesis and function. Rna 15 (9): 1640- 1651. doi: 10.1261/rna.1560209.
Sung H, Jeon S, Lee K-M, Han S, Song M et al. (2012). Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival. BMC Cancer 12 (1): 195-207. doi: 10.1186/1471-2407-12-195.
Tian Y, Simanshu DK, Ma JB, Park JE, Heo I et al. (2014). A phosphate-binding pocket within the platform-PAZ-connector helix cassette of human Dicer. Molecular Cell 53 (4): 606-616. doi: 10.1016/j.molcel.2014.01.003.
Tsutsumi A, Kawamata T, Izumi N, Seitz H, Tomari Y (2011). Recognition of the pre-miRNA structure by Drosophila Dicer-1. Nature Structural & Molecular Biology 18 (10): 1153- 1158. doi: 10.1038/nsmb.2125.
Wahid F, Shehzad A, Khan T, Kim YY (2010). MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochimica et Biophysica Acta 1803 (11): 1231-1243. doi: 10.1016/j. bbamcr.2010.06.013.
Wang L, Li L, Guo R, Li X, Lu Y et al. (2014). miR-101 promotes breast cancer cell apoptosis by targeting Janus kinase 2. Cellular Physiology Biochemistry 34 (2): 413-422. doi: 10.1159/000363010.
Wang R, Wang H-B, Hao CJ, Cui Y, Han X-C et al. (2012). MiR101 is involved in human breast carcinogenesis by targeting Stathmin1. PLoS One 7 (10): e46173-e46191. doi: 10.1371/ journal.pone.0046173.
Wazir U, Orakzai MM, Martin TA, Jiang WG, Mokbel K (2019). Correlation of TERT and stem cell markers in the context of human breast cancer. Cancer Genomics & Proteomics 16 (2): 121-127. doi: 10.21873/cgp.20117.
Wightman B, Ha I, Ruvkun G (1993). Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75 (5): 855-862. doi: 10.1016/0092-8674(93)90530-4.
Wu L, Belasco JG (2005). Micro-RNA regulation of the mammalian lin-28 gene during neuronal differentiation of embryonal carcinoma cells. Molecular Cellular Biology 25 (21): 9198- 9208. doi: 10.1128/MCB.25.21.9198-9208.2005.
Xiao J, Lin H, Luo X, Luo X, Wang Z (2011). miR-605 joins p53 network to form a p53: miR-605: Mdm2 positive feedback loop in response to stress. The EMBO Journal 30 (3): 524-532. doi: 10.1038/emboj.2010.347.
Xiong X, Kang X, Zheng Y, Yue S, Zhu S (2013). Identification of loop nucleotide polymorphisms affecting microRNA processing and function. Molecules and Cells 36 (6): 518-526. doi: 10.1007/ s10059-013-0171-1.
Yamagata K, Fujiyama S, Ito S, Ueda T, Murata T et al. (2014). Maturation of microRNA is hormonally regulated by a nuclear receptor. Molecular Cell 54 (3): 536. doi: 10.1016/j. molcel.2009.08.017.
Yan W, Gao X, Zhang S (2017). Association of miR-196a2 rs11614913 and miR-499 rs3746444 polymorphisms with cancer risk: a meta-analysis. Oncotarget 8 (69): 114344-114359. doi: 10.18632/oncotarget.22547.
Yan X, Chen X, Liang H, Deng T, Chen W et al. (2014). miR-143 and miR-145 synergistically regulate ERBB3 to suppress cell proliferation and invasion in breast cancer. Molecular Cancer 13: 220-234. doi: 10.1186/1476-4598-13-220.
Yang R, Schlehe B, Hemminki K, Sutter C, Bugert P et al. (2010). A genetic variant in the pre-miR-27a oncogene is associated with a reduced familial breast cancer risk. Breast Cancer Research and Treatment 121 (3): 693-702. doi: 10.1007/s10549-009- 0633-5.
Yi R, Qin Y, Macara IG, Cullen BR (2003). Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes & Development 17 (24): 3011-3016. doi: 10.1101/ gad.1158803.
Yu Z, Wang C, Wang M, Li Z, Casimiro MC et al. (2008). A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. The Journal of Cell Biology 182 (3): 509-517. doi: 10.1083/jcb.200801079.
Zeng Y, Cullen BR (2005). Efficient processing of primary microRNA hairpins by Drosha requires flanking nonstructured RNA sequences. Journal of Biological Chemistry 280 (30): 27595- 27603. doi: 10.1074/jbc.M504714200.
Zeng Y, Yi R, Cullen BR (2005). Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. The EMBO Journal 24 (1): 138-148. doi: 10.1038/ sj.emboj.7600491.
Zhang H, Kolb FA, Jaskiewicz L, Westhof E, Filipowicz W (2004). Single processing center models for human Dicer and bacterial RNase III. Cell 118 (1): 57-68. doi: 10.1016/j.cell.2004.06.017.
Zhang H, Zhang Y, Yan W, Wang W, Zhao X et al. (2017a). Association between three functional microRNA polymorphisms (miR-499 rs3746444, miR-196a rs11614913 and miR-146a rs2910164) and breast cancer risk: a meta-analysis. Oncotarget 8 (1): 393- 407. doi: 10.18632/oncotarget.13426.
Zhang H, Zhang Y, Zhao X, Ma X, Yan W et al. (2017b). Association of two microRNA polymorphisms miR-27 rs895819 and miR423 rs6505162 with the risk of cancer. Oncotarget 8 (29): 46969-46980. doi: 10.18632/oncotarget.16443.
Zhang N, Huo Q, Wang X, Chen X, Long L et al. (2013). A genetic variant in pre-miR-27a is associated with a reduced breast cancer risk in younger Chinese population. Gene 529 (1): 125- 130. doi: 10.1016/j.gene.2013.07.041.
Zhao H, Gao A, Zhang Z, Tian R, Luo A et al. (2015). Genetic analysis and preliminary function study of miR-423 in breast cancer. Tumor Biology 36 (6): 4763-4771. doi: 10.1007/s13277- 015-3126-7.
Zheng H, Song F, Zhang L, Yang D, Ji P et al. (2011). Genetic variants at the miR-124 binding site on the cytoskeleton-organizing IQGAP1 gene confer differential predisposition to breast cancer. International Journal of Oncology 38 (4): 1153-1161. doi: 10.3892/ijo.2011.940.
Zhou CH, Zhang XP, Liu F, Wang W (2014). Involvement of miR605 and miR-34a in the DNA damage response promotes apoptosis induction. Biophysical Journal 106 (8): 1792-1800. doi: 10.1016/j.bpj.2014.02.032.