Volume 10, Issue 1 (Vol.10 No.1 Apr 2021)                   rbmb.net 2021, 10(1): 20-29 | Back to browse issues page


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Bagheri M, Khansarinejad B, Mosayebi G, Moradabadi A, Mondanizadeh M. Alterations in The Plasma Expression of mir-15b, mir-195 and the Tumor-Suppressor Gene DLEU7 in Patients with B-Cell Chronic Lymphocytic Leukemia. rbmb.net 2021; 10 (1) :20-29
URL: http://rbmb.net/article-1-567-en.html
Department of Biotechnology and Molecular Medicine, Arak University of Medical Sciences, Arak, Iran & Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak,Iran.
Abstract:   (3750 Views)
Background : Chronic lymphocytic leukemia (CLL) is one of the most prevalent forms of leukemia in adults. Inactivation of the DLEU7 gene is frequently observed in patients with CLL. Furthermore, microRNAs (miRNAs) have been observed to have a critical role in the pathogenesis of several cancers, including leukemia. Considering the tumor-suppressive role of DLEU7, as well as the tumor suppressor or oncogenic role of microRNAs (miRNAs), the aim of the present study was to evaluate the potential miRNAs targeting the DLEU7 gene in B-cells and explore expression changes these genes in the plasma of B-CLL patients.

Methods: The miRNAs interacting with the DLEU7 gene were predicted and selected using bioinformatics tools. A total of 80 plasma samples were collected from 40 patients with B-cells and 40 healthy individuals, then subjected to RNA extraction and cDNA synthesis. The expression profiles of the predicted miRNAs and the DLEU7 gene in the plasma of B-CLL patients and healthy individuals were determined by RT-qPCR analysis.

Results:The bioinformatics prediction indicated that miR-15b and miR-195 target the DLEU7 gene. The expression levels of miR-15b and miR-195 were significantly higher in the plasma of patients with BCLL compared to the healthy individuals (91.6, p= 0.001) (169, p= 0.001). However, the expression level of the DLEU7 gene was found to be significantly lower in the patient group compared to healthy controls (0.304, p= 0.001).

Conclusions: Both miR-15b and miR-195, have the potential to function as novel and non-invasive biomarkers in the diagnosis and prognosis of patients with B-CLL.
Full-Text [PDF 431 kb]   (1463 Downloads)    
Type of Article: Original Article | Subject: Molecular Biology
Received: 2020/09/7 | Accepted: 2020/09/29 | Published: 2021/05/9

References
1. Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J of Med. 2005;352(8):804-15. [DOI:10.1056/NEJMra041720] [PMID]
2. Sgambati MT, Linet MS, Devesa S. Chronic lymphocytic leukemia epidemiological, familial, and genetic aspects. In: Cheson BD,ed. Chronic lymphocytic leukemia (2nd ed). New York: Marcal Dekker;2001:33-62.
3. Orfao A, Almeida J, Sanchez ML, San Miguel JF. Immunophenotypic diagnosis of leukemic B-cell chronic lymphoproliferative disorders other than chronic lymphocytic leukemia. Chronic Lymphocytic Leukemia. Contemporary Hematology. Humana Press, Totowa, NJ; 2004. [DOI:10.1007/978-1-59259-412-2_9]
4. Swerdlow S, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon. 4th Edition. 2008.
5. Zhang S, Kipps TJ. The pathogenesis of chronic lymphocytic leukemia. Annu Rev Pathol. 2014;9:103-118. [DOI:10.1146/annurev-pathol-020712-163955] [PMID] [PMCID]
6. Kiefer Y, Schulte C, Tiemann M, Bullerdiek J. Chronic lymphocytic leukemia-associated chromosomal abnormalities and miRNA deregulation. Appl Clin Genet. 2012;5:21-28. [DOI:10.2147/TACG.S18669] [PMID] [PMCID]
7. Caporaso N, Goldin L, Plass C, Calin G, Marti G, Bauer S, et al. Chronic lymphocytic leukaemia genetics overview. Br J Haematol. 2007;139(5):630-4. [DOI:10.1111/j.1365-2141.2007.06846.x] [PMID]
8. Döhner H, Stilgenbauer S, Benner A, Leupolt E, Kröber A, Bullinger L, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343(26):1910-6. [DOI:10.1056/NEJM200012283432602] [PMID]
9. Döhner H, Stilgenbauer S, Döhner K, Bentz M, Lichter P. Chromosome aberrations in B-cell chronic lymphocytic leukemia: reassessment based on molecular cytogenetic analysis. J Mol Med (Berl). 1999;77(2):266-81. [DOI:10.1007/s001090050350] [PMID]
10. Ouillette P, Erba H, Kujawski L, Kaminski M, Shedden K, Malek SN. Integrated genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion 13q14. Cancer Res. 2008;68(4):1012-21. [DOI:10.1158/0008-5472.CAN-07-3105] [PMID]
11. Hammarsund M, Corcoran MM, Wilson W, Zhu C, Einhorn S, Sangfelt O, et al. Characterization of a novel B‐CLL candidate gene-DLEU7-located in the 13q14 tumor suppressor locus. FEBS Lett. 2004;556(1-3):75-80. [DOI:10.1016/S0014-5793(03)01371-1]
12. Palamarchuk A, Efanov A, Nazaryan N, Santanam U, Alder H, Rassenti L, et al. 13q14 deletions in CLL involve cooperating tumor suppressors. Blood. 2010;115(19):3916-3922. [DOI:10.1182/blood-2009-10-249367] [PMID] [PMCID]
13. Pekarsky Y, Zanesi N, Croce CM, editors. Molecular basis of CLL. Semin Cancer Biol. 2010;20(6):370-6. [DOI:10.1016/j.semcancer.2010.09.003] [PMID] [PMCID]
14. Pekarsky Y, Zanesi N, Aqeilan RI, Croce CM. Animal models for chronic lymphocytic leukemia. J Cell Biochem. 2007;100(5):1109-18. [DOI:10.1002/jcb.21147] [PMID]
15. Salarinia R, Sahebkar A, Peyvandi M, Reza Mirzaei H, Reza Jaafari M, Matbou Riahi M, et al. Epi-drugs and Epi-miRs: moving beyond current cancer therapies. Current cancer drug targets. 2016;16(9):773-788. [DOI:10.2174/1568009616666151207110143] [PMID]
16. Esmaili MA, Kazemi A, Zaker F, Faranoush M, Rezvany MR. Effects of Reduced Mir-24 Expression on Plasma Methotrexate Levels, Therapy-Related Toxicities, and Patient Outcomes in Pediatric Acute Lymphoblastic Leukemia. Reports of Biochemistry & Molecular Biology. 2020;8(4):358-365.
17. Simonian M, Mosallayi M, Mirzaei H. Circulating miR-21 as novel biomarker in gastric cancer: diagnostic and prognostic biomarker. J Cancer Res Ther. 2018;14(2):475.
18. Bayatiani MR, Ahmadi A, Aghabozorgi R, Seif F. Concomitant Up-Regulation of Hsa-Mir-374 and Down-Regulation of Its Targets, GSK-3β and APC, in Tissue Samples of Colorectal Cancer. Reports of Biochemistry and Molecular Biology. 2021,9(4):408-416. [DOI:10.52547/rbmb.9.4.408] [PMID] [PMCID]
19. Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov V, et al. Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res. 2006;66(24):11590-3. [DOI:10.1158/0008-5472.CAN-06-3613] [PMID]
20. Balatti V, Pekarky Y, Rizzotto L, Croce CM. miR deregulation in CLL. Adv Exp Med Biol. 2013;792:309-25. [DOI:10.1007/978-1-4614-8051-8_14] [PMID] [PMCID]
21. Shaker O, Mahfouz H, Salama A, Medhat E. Long Non-Coding HULC and miRNA-372 as Diagnostic Biomarkers in Hepatocellular Carcinoma. Reports of Biochemistry & Molecular Biology. 2020;9(2):230-240. [DOI:10.29252/rbmb.9.2.230] [PMID] [PMCID]
22. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105(30):10513-8. [DOI:10.1073/pnas.0804549105] [PMID] [PMCID]
23. Wang L, Zhang S, Xu Z, Zhang J, Li L, Zhao G. The diagnostic value of microRNA-4787-5p and microRNA-4306 in patients with acute aortic dissection. Am J Transl Res. 2017;9(11):5138-5149.
24. Parvaee P, Sarmadian H, Khansarinejad B, Amini M, Mondanizadeh M. Plasma level of microRNAs, miR-107, miR-194 and miR-210 as potential biomarkers for diagnosis intestinal-type gastric cancer in human. Asian Pac J Cancer Prev. 2019;20(5):1421-1426. [DOI:10.31557/APJCP.2019.20.5.1421] [PMID] [PMCID]
25. Fernando TR, Rodriguez-Malave NI, Rao DS. MicroRNAs in B cell development and malignancy. J Hematol Oncol. 2012;5:7. [DOI:10.1186/1756-8722-5-7] [PMID] [PMCID]
26. Brase JC, Wuttig D, Kuner R, Sültmann H. Serum microRNAs as non-invasive biomarkers for cancer. Molecular cancer. 2010;9:306. [DOI:10.1186/1476-4598-9-306] [PMID] [PMCID]
27. Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST©) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002;30(9):e36. [DOI:10.1093/nar/30.9.e36] [PMID] [PMCID]
28. Wozniak MB, Scelo G, Muller DC, Mukeria A, Zaridze D, Brennan P. Circulating microRNAs as non-invasive biomarkers for early detection of non-small-cell lung cancer. PLoS One. 2015;10(5):e0125026. [DOI:10.1371/journal.pone.0125026] [PMID] [PMCID]
29. Mraz M, Pospisilova S, Malinova K, Slapak I, Mayer J. MicroRNAs in chronic lymphocytic leukemia pathogenesis and disease subtypes. Leuk Lymphoma. 2009;50(3):506-9. [DOI:10.1080/10428190902763517] [PMID]
30. Rossi S, Shimizu M, Barbarotto E, Nicoloso MS, Dimitri F, Sampath D, et al. microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival. Blood. 2010;116(6):945-52. [DOI:10.1182/blood-2010-01-263889] [PMID] [PMCID]
31. 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. [DOI:10.1002/jcp.25799] [PMID]
32. Zanette DL, Rivadavia F, Molfetta GA, Barbuzano FG, Proto-Siqueira R, Silva Jr WA, et al. miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia. Braz J Med Biol Res. 2007;40(11):1435-40. [DOI:10.1590/S0100-879X2007001100003] [PMID]
33. Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, et al. MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A. 2008;105(13):5166-71. [DOI:10.1073/pnas.0800121105] [PMID] [PMCID]
34. 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(10):327-332. [DOI:10.1038/cgt.2016.34] [PMID]
35. Li S, Moffett HF, Lu J, Werner L, Zhang H, Ritz J, et al. MicroRNA expression profiling identifies activated B cell status in chronic lymphocytic leukemia cells. PLoS One. 2011;6(3):e16956. [DOI:10.1371/journal.pone.0016956] [PMID] [PMCID]
36. Kedmi M, Ben-Chetrit N, Körner C, Mancini M, Ben-Moshe NB, Lauriola M, et al. EGF induces microRNAs that target suppressors of cell migration: miR-15b targets MTSS1 in breast cancer. Sci Signal. 2015;8(368):ra29. [DOI:10.1126/scisignal.2005866] [PMID]
37. Liu AM, Yao T-J, Wang W, Wong K-F, Lee NP, Fan ST, et al. Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open. 2012;2(2):e000825. [DOI:10.1136/bmjopen-2012-000825] [PMID] [PMCID]
38. Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S, et al. miR‐15b and miR‐16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer. 2008;123(2):372-379. [DOI:10.1002/ijc.23501] [PMID]
39. Zheng X, Chopp M, Lu Y, Buller B, Jiang F. MiR-15b and miR-152 reduce glioma cell invasion and angiogenesis via NRP-2 and MMP-3. Cancer Lett. 2013;329(2):146-54. [DOI:10.1016/j.canlet.2012.10.026] [PMID] [PMCID]
40. Zhang Y, Huang F, Wang J, Peng L, Luo H. MiR-15b mediates liver cancer cells proliferation through targeting BCL-2. Int J Clin Exp Pathol. 2015;8(12):15677-15683.
41. Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Newell J, Kerin MJ. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg. 2010;251(3):499-505. [DOI:10.1097/SLA.0b013e3181cc939f] [PMID]
42. Soon PSH, Tacon LJ, Gill AJ, Bambach CP, Sywak MS, Campbell PR, et al. miR-195 and miR-483-5p identified as predictors of poor prognosis in adrenocortical cancer. Clin Cancer Res. 2009;15(24):7684-7692. [DOI:10.1158/1078-0432.CCR-09-1587] [PMID]
43. Xu T, Zhu Y, Xiong Y, Ge YY, Yun JP, Zhuang SM. MicroRNA‐195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology. 2009;50(1):113-21. [DOI:10.1002/hep.22919] [PMID]
44. Liu L, Chen L, Xu Y, Li R, Du X. microRNA-195 promotes apoptosis and suppresses tumorigenicity of human colorectal cancer cells. Biochem Biophys Res Commun. 2010;400(2):236-40. [DOI:10.1016/j.bbrc.2010.08.046] [PMID]
45. Wang Y, Mu L, Huang M. MicroRNA‑195 suppresses rectal cancer growth and metastasis via regulation of the PI3K/AKT signaling pathway. Mol Med Rep. 2019;20(5):4449-4458. [DOI:10.3892/mmr.2019.10717] [PMID] [PMCID]
46. Yu X, Zhang Y, Cavazos D, Ma X, Zhao Z, Du L, et al. miR-195 targets cyclin D3 and survivin to modulate the tumorigenesis of non-small cell lung cancer. Cell Death Dis. 2018;9(2):193. [DOI:10.1038/s41419-017-0219-9] [PMID] [PMCID]

Add your comments about this article : Your username or Email:
CAPTCHA

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2015 All Rights Reserved | Reports of Biochemistry and Molecular Biology

Designed & Developed by : Yektaweb