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Nateghi, B., Behshood, P., Fathullahzadeh, S., & Mardanshah, O. (2019). Circulating miR-95 Is a Potential Biomarker of Chronic Lymphocytic Leukemia. Research in Molecular Medicine (RMM), 6(2). https://doi.org/10.18502/rmm.v6i2.4537
https://doi.org/10.18502/rmm.v6i2.4537
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Behnaz Nateghi
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-
Parisa Behshood
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Sima Fathullahzadeh
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-
Omid Mardanshah
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Published Date
- May 27, 2019
Circulating miR-95 Is a Potential Biomarker of Chronic Lymphocytic Leukemia
Abstract
Background: MicroRNAs (miRNAs) have crucial roles in cellular and molecular processes related to different malignancies including chronic lymphocytic leukemia(CLL). Studies revealed altered miR-95 expression in several diseases. Long noncoding RNAs (lncRNAs) are a heterogeneous group of non-coding and regulatory
RNAs. The present study was conducted to investigate the association of miR-95 expression with CLL by quantitative real-time PCR.
Materials and Methods: Sixty samples, including 30 CLL and 30 healthy controls, were sampled during a period of 4 months. The expression of miR-95 was evaluated by quantitative real-time PCR in peripheral blood mononuclear cells from patients with CLL and in healthy subjects. Additionally, in silico pathway enrichment analysis was performed on validated and predicted targets of miR-95 in several databases, including miRecords and miRTarBase, while the interactions between predicted putative lncRNAs and genes and miRNA expression were examined with miRWalk.
Results: The expression of miR-95 was found to be significantly reduced in patients with CLL compared to that in healthy controls (P < 0.005).
Conclusion: miR-95 showed potential as a biomarker for the early diagnosis of patients with CLL. LncRNAs play a significant role in regulating cellular evolution, differentiation, and other processes and may be important regulators in tumorigenesis.
References
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[27] Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2002;99:15524-29.
[28] Di Lisi L, Sánchez-Beato M, Gómez-López G, Rodríguez ME, Montes-Moreno S, Mollejo M, et al. MicroRNA signatures in B-cell lymphomas. Blood Cancer J. 2012;2:e57.
[29] Chen X, Chen S, Hang W, Huang H, Ma H. MiR-95 induces proliferation and chemo-or radioresistance through directly targeting sorting nexin1 (SNX1) in non-small cell lung cancer. Biomed Pharmacother. 2014;68:589-95.
[30] Ronchetti D, Manzoni M, Agnelli L, Vinci C, Fabris S, Cutrona G, et al. lncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome. Blood Cancer J. 2016;6:e468.
[2] Mikaelsson E. Towards new therapeutic targets: identification of novel tumor markers in chronic lymphocytic leukemia. Inst för onkologi-patologi/Dept of Oncology-Pathology; 2010.
[3] Fathullahzadeh S, Mirzaei H, Honardoost MA, Sahebkar A, Salehi M. Circulating microRNA-192 as a diagnostic biomarker in human chronic lymphocytic leukemia. Cancer Gene Ther. 2016;23:327-32.
[4] Pekarsky Y, Croce CM. Role of miR-15/16 in CLL. Cell Death Differ. 2015;22:6.
[5] Cui Z, Lin D. Circulating miRNAs: potential biomarkers for diagnosis and prognosis prediction of hematological malignancies. J Leuk. 2014. Available from; https://www.omicsonline.org/open-access/
circulating-mirnas-potential-biomarkers-for-diagnosis-and-prognosis-prediction-of-hematologicalmalignancies-2329-6917.1000140.php?aid=29710.
[6] Reddy KB. MicroRNA (miRNA) in cancer. Cancer Cell Int. 2015;15:38.
[7] Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 2004;101(9):2999-3004.
[8] Mirzaei H, Fathullahzadeh S, Khanmohammadi R, Darijani M, Momeni F, Masoudifar A, et al. State of the art in microRNA as diagnostic and therapeutic biomarkers in chronic lymphocytic leukemia. J Cell Physiol. 2018;233(2):888-900.
[9] Qin J, Chen JX, Zhu Z, Teng JA. Genistein inhibits human colorectal cancer growth and suppresses miR-95, Akt and SGK1. Cell Physiol Biochem. 2015;35:2069-77.
[10] Zhang J, Zhang C, Hu L, He Y, Shi Z, Tang S, et al. Abnormal expression of miR-21 and miR-95 in cancer stem-like cells is associated with radioresistance of lung cancer. Cancer Invest. 2015;33:165-71.
[11] Huang Z, Huang S, Wang Q, Liang L, Ni S, Wang L, et al. MicroRNA-95 promotes cell proliferation and targets sorting Nexin 1 in human colorectal carcinoma. Cancer Res. 2011;71:2582-89.
[12] Niu J, Sun Y, Guo Q, Niu D, Liu B. Serum miR-95-3p is a diagnostic and prognostic marker for osteosarcoma. SpringerPlus. 2016;5:1947.
[13] Huang X, Taeb S, Jahangiri S, Emmenegger U, Tran E, Bruc J, et al. miRNA-95 mediates radioresistance in tumors by targeting the sphingolipid phosphatase SGPP1. Cancer Res. 2013;73:6972-86.
[14] Fan B, Jiao B H, Fa F S, Lu SK, Song J, Guo CY, et al. Downregulation of miR-95-3p inhibits proliferation, and invasion promoting apoptosis of glioma cells by targeting CELF2. Int J Oncol. 2015;47:1025-33.
[15] Li M, Li J, Ding X, He M, Cheng SY. MicroRNA and cancer. AAPS J. 2010;12:309-17.
[16] Shehata M, Schnabl S, Demirtas D, Hilgarth M, Hubmann R, Ponath E, et al. Reconstitution of PTEN activity by CK2 inhibitors and interference with the PI3-K/Akt cascade counteract the antiapoptotic effect of human stromal cells in chronic lymphocytic leukemia. Blood. 2010;116(14):2513-21.
[17] Karapetyan AR, Buiting C, Kuiper RA, Coolen MW. Regulatory roles for long ncRNA and mRNA. Cancers.
2013;5:462-90.
[18] Blume C, Hotz-Wagenblatt A, Hüllein J, Sellner L, Jethwa A, Stolz T, et al. p53-dependent non-coding RNA networks in chronic lymphocytic leukemia. Leukemia. 2015;29(10).
[19] Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol. 2011;21:354-61.
[20] Nobili L, Lionetti M, Neri A. Long non-coding RNAs in normal and malignant hematopoiesis. Oncotarget.
2016;7:50666.
[21] Negrini M, Cutrona G, Bassi C, Fabris S, Zagatti B, Colombo M, et al. microRNAome expression in chronic lymphocytic leukemia: comparison with normal B-cell subsets and correlations with prognostic and clinical parameters. Clin Cancer Res. 2014;10:723.
[22] Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C T method. Nat Protoc. 2008;3(6):1101.
[23] Xiao F, Zuo Z, Cai G, Kang S, Gao X, Li T. miRecords: an integrated resource for microRNA–target interactions. Nucleic Acids Res. 2008;37(suppl_1):D105-10.
[24] Hsu SD, Lin FM, Wu WY, Liang C, Huang WC, Chan WL, et al. miRTarBase: a database curates experimentally validated microRNA–target interactions. Nucleic Acids Res. 2010;39(suppl_1):D163-9.
[25] Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44.
[26] Zhu J, Fu H, Wu Y, Zheng X. Function of lncRNAs and approaches to lncRNA-protein interactions. Science China Life Sciences. 2013;56:876-85.
[27] Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2002;99:15524-29.
[28] Di Lisi L, Sánchez-Beato M, Gómez-López G, Rodríguez ME, Montes-Moreno S, Mollejo M, et al. MicroRNA signatures in B-cell lymphomas. Blood Cancer J. 2012;2:e57.
[29] Chen X, Chen S, Hang W, Huang H, Ma H. MiR-95 induces proliferation and chemo-or radioresistance through directly targeting sorting nexin1 (SNX1) in non-small cell lung cancer. Biomed Pharmacother. 2014;68:589-95.
[30] Ronchetti D, Manzoni M, Agnelli L, Vinci C, Fabris S, Cutrona G, et al. lncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome. Blood Cancer J. 2016;6:e468.