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Regulatory Role of miR-15a-5p and miR-16-5p in Suppressing Acute Myeloid Leukemia Cell Growth through Target Gene Interaction

Year 2026, Volume: 28 Issue: 1 , 84 - 92 , 25.04.2026
https://doi.org/10.18678/dtfd.1822082
https://izlik.org/JA53SE93KB

Abstract

Aim: This study aimed to investigate the functional effects of miR-15a-5p and miR-16-5p in AML cell lines (HL-60 and NB4), focusing on their regulation of key target genes. Material and Methods: We initially transfected miR-15a-5p and miR-16-5p mimics into AML cell lines to investigate their regulatory roles in fundamental cellular processes. After the transfection, the potential target genes of these miRNAs were identified through several in silico prediction tools, allowing us to focus on biologically relevant candidates. To evaluate how these miRNA–target gene axes may influence AML-related mechanisms, the expression levels of the selected genes were subsequently analyzed in mimic-transfected cells using quantitative expression assays. Results: Study results showed that transfection of miR-15a-5p and miR-16-5p miRNA mimics led to a marked suppression of HL-60 and NB4 AML cell proliferation, indicating that both miRNAs exert inhibitory effects on leukemic cell growth. Consistent with this observation, IGF1R expression was significantly downregulated at the mRNA level in AML cells transfected with either miRNA mimics. This coordinated reduction suggests that IGF1R may function as a critical downstream effector of these miRNAs. Conclusion: These findings suggest that miR-15a-5p and miR-16-5p may function as tumor suppressors in AML, with potential therapeutic implications. Additionally, the interactions between miR-15a-5p/miR-16-5p/IGF1R may serve as specific biomarkers for new therapeutic targets in AML. Overall, this study highlights miR-15a-5p and miR-16-5p as promising targets for the development of novel AML therapies.

Project Number

37138

References

  • Shimony S, Stahl M, Stone RM. Acute myeloid leukemia: 2025 update on diagnosis, risk-stratification, and management. Am J Hematol. 2025;100(5):860-91. doi:10.1002/ajh.27625.
  • Mrózek K, Bloomfield CD. Chromosome aberrations, gene mutations and expression changes, and prognosis in adult acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2006:169-77. doi:10.1182/asheducation-2006.1.169.
  • Kaya M. Bioinformatics evaluation of the circRNA–miRNA–mRNA axis in cervical squamous cell carcinoma. Explor Med. 2024;5:553-65. doi:10.37349/emed.2024.00239.
  • Kaya M, Karataş ÖF. Larenks kanseri ve mikroRNA’lar arasındaki ilişki [The relationship between larynx cancer and microRNAs]. Van Tıp Derg. 2020;27(4):535-41. Turkish. doi:10.5505/vtd.2020.80947.
  • Kaya M, Abuaisha A, Süer İ, Alptekin MS, Abanoz F, Emiroğlu S, et al. Overexpression of CDC25A, AURKB, and TOP2A genes could be an important clue for luminal a breast cancer. Eur J Breast Health. 2024;20(4):284-91. doi:10.4274/ejbh.galenos.2024.2024-4-3.
  • Kaya M, Abuaisha A, Suer I, Emiroglu S, Önder S, Onay Ucar E, et al. Let-7b-5p sensitizes breast cancer cells to doxorubicin through Aurora Kinase B. PLoS One. 2025;20(1):e0307420. doi:10.1371/journal.pone.0307420.
  • 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 U S A. 2002;99(24):15524-9. doi:10.1073/pnas.242606799.
  • Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102(39):13944-9. doi:10.1073/pnas.0506654102.
  • Guo H, Ma K, Hao W, Jiao Y, Li P, Chen J, et al. mir15a/mir16-1 cluster and its novel targeting molecules negatively regulate cardiac hypertrophy. Clin Transl Med. 2020;10(8):e242. doi:10.1002/ctm2.242.
  • Bollaert E, Claus M, Vandewalle V, Lenglez S, Essaghir A, Demoulin JB, et al. MiR-15a-5p confers chemoresistance in acute myeloid leukemia by inhibiting autophagy induced by daunorubicin. Int J Mol Sci. 2021;22(10):5153. doi:10.3390/ijms22105153.
  • Liu T, Xu Z, Ou D, Liu J, Zhang J. The miR-15a/16 gene cluster in human cancer: a systematic review. J Cell Physiol. 2019;234(5):5496-506. doi:10.1002/jcp.27342.
  • Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, et al. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008;14(11):1271-7. doi:10.1038/nm.1880.
  • Patel N, Garikapati KR, Pandita RK, Singh DK, Pandita TK, Bhadra U, et al. miR-15a/miR-16 down-regulates BMI1, impacting Ub-H2A mediated DNA repair and breast cancer cell sensitivity to doxorubicin. Sci Rep. 2017;7(1):4263. doi:10.1038/s41598-017-02800-2.
  • Bandi N, Zbinden S, Gugger M, Arnold M, Kocher V, Hasan L, et al. miR-15a and miR-16 are implicated in cell cycle regulation in a Rb-dependent manner and are frequently deleted or down-regulated in non-small cell lung cancer. Cancer Res. 2009;69(13):5553-9. doi:10.1158/0008-5472.CAN-08-4277.
  • 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):372-9. doi:10.1002/ijc.23501.
  • Chang L, Zhou G, Soufan O, Xia J. miRNet 2.0: network-based visual analytics for miRNA functional analysis and systems biology. Nucleic Acids Res. 2020;48(W1):W244-51. doi:10.1093/nar/gkaa467.
  • Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. Elife. 2015;4:e05005. doi:10.7554/eLife.05005.
  • Chen Y, Wang X. miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res. 2020;48(D1):D127-31. doi:10.1093/nar/gkz757.
  • Evangelista JE, Xie Z, Marino GB, Nguyen N, Clarke DJB, Ma'ayan A. Enrichr-KG: bridging enrichment analysis across multiple libraries. Nucleic Acids Res. 2023;51(W1):W168-79. doi:10.1093/nar/gkad393.
  • Szklarczyk D, Kirsch R, Koutrouli M, Nastou K, Mehryary F, Hachilif R, et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 2023;51(D1):D638-46. doi:10.1093/nar/gkac1000.
  • Birnie GD. The HL60 cell line: a model system for studying human myeloid cell differentiation. Br J Cancer Suppl. 1988;9:41-5.
  • Zhao M, Wang J, Qu M, Zhao Y, Wang H, Ke Y, et al. OGP46 induces differentiation of acute myeloid leukemia cells via different optimal signaling pathways. Front Cell Dev Biol. 2021;9:652972. doi:10.3389/fcell.2021.652972.
  • Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL. Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics. 2012;13:134. doi:10.1186/1471-2105-13-134.
  • Dyer SC, Austine-Orimoloye O, Azov AG, Barba M, Barnes I, Barrera-Enriquez VP, et al. Ensembl 2025. Nucleic Acids Res. 2025;53(D1):D948-57. doi:10.1093/nar/gkae1071.
  • Wu J, Liu L, Jin H, Li Q, Wang S, Peng B. LncSNHG3/miR-139-5p/BMI1 axis regulates proliferation, migration, and invasion in hepatocellular carcinoma. Onco Targets Ther. 2019;12:6623-38.10.2147/OTT.S196630.
  • Chang L, Guo R, Yuan Z, Shi H, Zhang D. LncRNA HOTAIR regulates CCND1 and CCND2 expression by sponging miR-206 in ovarian cancer. Cell Physiol Biochem. 2018;49(4):1289-303. doi:10.1159/000493408.
  • Luo Q, Wei C, Li X, Li J, Chen L, Huang Y, et al. MicroRNA-195-5p is a potential diagnostic and therapeutic target for breast cancer. Oncol Rep. 2014;31(3):1096-102. doi:10.3892/or.2014.2971.
  • Feng X, Wu Z, Wu Y, Hankey W, Prior TW, Li L, et al. Cdc25A regulates matrix metalloprotease 1 through Foxo1 and mediates metastasis of breast cancer cells. Mol Cell Biol. 2011;31(16):3457-71. doi:10.1128/MCB.05523-11.
  • Lim S, Kim Y, Lee SB, Kang HG, Kim DH, Park JW, et al. Inhibition of Chk1 by miR-320c increases oxaliplatin responsiveness in triple-negative breast cancer. Oncogenesis. 2020;9(10):91. doi:10.1038/s41389-020-00275-x.
  • Sun HZ, Wu SF, Tu ZH. Knockdown of IGF-IR by antisense oligodeoxynucleotide auguments the sensitivity of bladder cancer cells to mitomycin. Acta Pharmacol Sin. 2001;22(9):841-6.
  • Wang Q, Chen Y, Lu H, Wang H, Feng H, Xu J, et al. Quercetin radiosensitizes non-small cell lung cancer cells through the regulation of miR-16-5p/WEE1 axis. IUBMB Life. 2020;72(5):1012-22. doi:10.1002/iub.2242.
  • Ramadan SM, Suciu S, Stevens-Kroef MJPL, Willemze R, Amadori S, de Witte T, et al. Survival improvement over time of 960 s-AML patients included in 13 EORTC-GIMEMA-HOVON trials. Cancers (Basel). 2020;12(11):3334. doi:10.3390/cancers12113334.
  • Hosono N. The new era of AML therapy: current standards and emerging targets. Int J Clin Oncol. 2026;Epub ahead of print. doi:10.1007/s10147-026-03038-7.
  • Kaya M, Suer I, Ozgur E, Capik O, Karatas OF, Ozturk S, et al. miR-145-5p suppresses cell proliferation by targeting IGF1R and NRAS genes in multiple myeloma cells. Turk J Biochem. 2023;48(5):563-9. doi:10.1515/tjb-2023-0042.
  • Chava S, Reynolds CP, Pathania AS, Gorantla S, Poluektova LY, Coulter DW, et al. miR-15a-5p, miR-15b-5p, and miR-16-5p inhibit tumor progression by directly targeting MYCN in neuroblastoma. Mol Oncol. 2020;14(1):180-96. doi:10.1002/1878-0261.12588.
  • Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ. 2010;17(2):215-20. doi:10.1038/cdd.2009.69.
  • Bhattacharya R, Nicoloso M, Arvizo R, Wang E, Cortez A, Rossi S, et al. MiR-15a and MiR-16 control Bmi-1 expression in ovarian cancer. Cancer Res. 2009;69(23):9090-5. doi:10.1158/0008-5472.CAN-09-2552.
  • Sueur G, Boutet A, Gotanègre M, Mansat-De Mas V, Besson A, Manenti S, et al. STAT5-dependent regulation of CDC25A by miR-16 controls proliferation and differentiation in FLT3-ITD acute myeloid leukemia. Sci Rep. 2020;10(1):1906. doi:10.1038/s41598-020-58651-x.
  • Guven DC, Ahmed J, Stephen B, Naing A. IGF-1R inhibitors in cancer: A review of available evidence and future outlook. Crit Rev Oncol Hematol. 2025;214:104809. doi:10.1016/j.critrevonc.2025.104809.
  • Wahner Hendrickson AE, Haluska P, Schneider PA, Loegering DA, Peterson KL, Attar R, et al. Expression of insulin receptor isoform A and insulin-like growth factor-1 receptor in human acute myelogenous leukemia: effect of the dual-receptor inhibitor BMS-536924 in vitro. Cancer Res. 2009;69(19):7635-43. doi:10.1158/0008-5472.CAN-09-0511.
  • Reyes-Carmona J. Insights on Bmi-1 therapeutic targeting in head and neck cancers. Oncol Res. 2025;33(2):301-7. doi:10.32604/or.2024.053764.
  • Saudy NS, Fawzy IM, Azmy E, Goda EF, Eneen A, Abdul Salam EM. BMI1 gene expression in myeloid leukemias and its impact on prognosis. Blood Cells Mol Dis. 2014;53(4):194-8. doi:10.1016/j.bcmd.2014.07.002.
  • Shen T, Huang S. The role of Cdc25A in the regulation of cell proliferation and apoptosis. Anticancer Agents Med Chem. 2012;12(6):631-9. doi:10.2174/187152012800617678.
  • Liu XM, Chen F, Zhang F, Xi HT, Zhao JZ. Knockdown of Chk1 inhibits proliferation and promotes apoptosis in mouse granulosa cells and its regulation mechanism by miR-15a and miR-16. In Vitro Cell Dev Biol Anim. 2022;58(7):579-86. doi:10.1007/s11626-022-00705-7.
  • Lovat F, Nigita G, Distefano R, Nakamura T, Gasparini P, Tomasello L, et al. Combined loss of function of two different loci of miR-15/16 drives the pathogenesis of acute myeloid leukemia. Proc Natl Acad Sci U S A. 2020;117(22):12332-40.10.1073/pnas.2003597117.

Year 2026, Volume: 28 Issue: 1 , 84 - 92 , 25.04.2026
https://doi.org/10.18678/dtfd.1822082
https://izlik.org/JA53SE93KB

Abstract

Project Number

37138

References

  • Shimony S, Stahl M, Stone RM. Acute myeloid leukemia: 2025 update on diagnosis, risk-stratification, and management. Am J Hematol. 2025;100(5):860-91. doi:10.1002/ajh.27625.
  • Mrózek K, Bloomfield CD. Chromosome aberrations, gene mutations and expression changes, and prognosis in adult acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2006:169-77. doi:10.1182/asheducation-2006.1.169.
  • Kaya M. Bioinformatics evaluation of the circRNA–miRNA–mRNA axis in cervical squamous cell carcinoma. Explor Med. 2024;5:553-65. doi:10.37349/emed.2024.00239.
  • Kaya M, Karataş ÖF. Larenks kanseri ve mikroRNA’lar arasındaki ilişki [The relationship between larynx cancer and microRNAs]. Van Tıp Derg. 2020;27(4):535-41. Turkish. doi:10.5505/vtd.2020.80947.
  • Kaya M, Abuaisha A, Süer İ, Alptekin MS, Abanoz F, Emiroğlu S, et al. Overexpression of CDC25A, AURKB, and TOP2A genes could be an important clue for luminal a breast cancer. Eur J Breast Health. 2024;20(4):284-91. doi:10.4274/ejbh.galenos.2024.2024-4-3.
  • Kaya M, Abuaisha A, Suer I, Emiroglu S, Önder S, Onay Ucar E, et al. Let-7b-5p sensitizes breast cancer cells to doxorubicin through Aurora Kinase B. PLoS One. 2025;20(1):e0307420. doi:10.1371/journal.pone.0307420.
  • 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 U S A. 2002;99(24):15524-9. doi:10.1073/pnas.242606799.
  • Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102(39):13944-9. doi:10.1073/pnas.0506654102.
  • Guo H, Ma K, Hao W, Jiao Y, Li P, Chen J, et al. mir15a/mir16-1 cluster and its novel targeting molecules negatively regulate cardiac hypertrophy. Clin Transl Med. 2020;10(8):e242. doi:10.1002/ctm2.242.
  • Bollaert E, Claus M, Vandewalle V, Lenglez S, Essaghir A, Demoulin JB, et al. MiR-15a-5p confers chemoresistance in acute myeloid leukemia by inhibiting autophagy induced by daunorubicin. Int J Mol Sci. 2021;22(10):5153. doi:10.3390/ijms22105153.
  • Liu T, Xu Z, Ou D, Liu J, Zhang J. The miR-15a/16 gene cluster in human cancer: a systematic review. J Cell Physiol. 2019;234(5):5496-506. doi:10.1002/jcp.27342.
  • Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, et al. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008;14(11):1271-7. doi:10.1038/nm.1880.
  • Patel N, Garikapati KR, Pandita RK, Singh DK, Pandita TK, Bhadra U, et al. miR-15a/miR-16 down-regulates BMI1, impacting Ub-H2A mediated DNA repair and breast cancer cell sensitivity to doxorubicin. Sci Rep. 2017;7(1):4263. doi:10.1038/s41598-017-02800-2.
  • Bandi N, Zbinden S, Gugger M, Arnold M, Kocher V, Hasan L, et al. miR-15a and miR-16 are implicated in cell cycle regulation in a Rb-dependent manner and are frequently deleted or down-regulated in non-small cell lung cancer. Cancer Res. 2009;69(13):5553-9. doi:10.1158/0008-5472.CAN-08-4277.
  • 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):372-9. doi:10.1002/ijc.23501.
  • Chang L, Zhou G, Soufan O, Xia J. miRNet 2.0: network-based visual analytics for miRNA functional analysis and systems biology. Nucleic Acids Res. 2020;48(W1):W244-51. doi:10.1093/nar/gkaa467.
  • Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. Elife. 2015;4:e05005. doi:10.7554/eLife.05005.
  • Chen Y, Wang X. miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res. 2020;48(D1):D127-31. doi:10.1093/nar/gkz757.
  • Evangelista JE, Xie Z, Marino GB, Nguyen N, Clarke DJB, Ma'ayan A. Enrichr-KG: bridging enrichment analysis across multiple libraries. Nucleic Acids Res. 2023;51(W1):W168-79. doi:10.1093/nar/gkad393.
  • Szklarczyk D, Kirsch R, Koutrouli M, Nastou K, Mehryary F, Hachilif R, et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 2023;51(D1):D638-46. doi:10.1093/nar/gkac1000.
  • Birnie GD. The HL60 cell line: a model system for studying human myeloid cell differentiation. Br J Cancer Suppl. 1988;9:41-5.
  • Zhao M, Wang J, Qu M, Zhao Y, Wang H, Ke Y, et al. OGP46 induces differentiation of acute myeloid leukemia cells via different optimal signaling pathways. Front Cell Dev Biol. 2021;9:652972. doi:10.3389/fcell.2021.652972.
  • Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL. Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics. 2012;13:134. doi:10.1186/1471-2105-13-134.
  • Dyer SC, Austine-Orimoloye O, Azov AG, Barba M, Barnes I, Barrera-Enriquez VP, et al. Ensembl 2025. Nucleic Acids Res. 2025;53(D1):D948-57. doi:10.1093/nar/gkae1071.
  • Wu J, Liu L, Jin H, Li Q, Wang S, Peng B. LncSNHG3/miR-139-5p/BMI1 axis regulates proliferation, migration, and invasion in hepatocellular carcinoma. Onco Targets Ther. 2019;12:6623-38.10.2147/OTT.S196630.
  • Chang L, Guo R, Yuan Z, Shi H, Zhang D. LncRNA HOTAIR regulates CCND1 and CCND2 expression by sponging miR-206 in ovarian cancer. Cell Physiol Biochem. 2018;49(4):1289-303. doi:10.1159/000493408.
  • Luo Q, Wei C, Li X, Li J, Chen L, Huang Y, et al. MicroRNA-195-5p is a potential diagnostic and therapeutic target for breast cancer. Oncol Rep. 2014;31(3):1096-102. doi:10.3892/or.2014.2971.
  • Feng X, Wu Z, Wu Y, Hankey W, Prior TW, Li L, et al. Cdc25A regulates matrix metalloprotease 1 through Foxo1 and mediates metastasis of breast cancer cells. Mol Cell Biol. 2011;31(16):3457-71. doi:10.1128/MCB.05523-11.
  • Lim S, Kim Y, Lee SB, Kang HG, Kim DH, Park JW, et al. Inhibition of Chk1 by miR-320c increases oxaliplatin responsiveness in triple-negative breast cancer. Oncogenesis. 2020;9(10):91. doi:10.1038/s41389-020-00275-x.
  • Sun HZ, Wu SF, Tu ZH. Knockdown of IGF-IR by antisense oligodeoxynucleotide auguments the sensitivity of bladder cancer cells to mitomycin. Acta Pharmacol Sin. 2001;22(9):841-6.
  • Wang Q, Chen Y, Lu H, Wang H, Feng H, Xu J, et al. Quercetin radiosensitizes non-small cell lung cancer cells through the regulation of miR-16-5p/WEE1 axis. IUBMB Life. 2020;72(5):1012-22. doi:10.1002/iub.2242.
  • Ramadan SM, Suciu S, Stevens-Kroef MJPL, Willemze R, Amadori S, de Witte T, et al. Survival improvement over time of 960 s-AML patients included in 13 EORTC-GIMEMA-HOVON trials. Cancers (Basel). 2020;12(11):3334. doi:10.3390/cancers12113334.
  • Hosono N. The new era of AML therapy: current standards and emerging targets. Int J Clin Oncol. 2026;Epub ahead of print. doi:10.1007/s10147-026-03038-7.
  • Kaya M, Suer I, Ozgur E, Capik O, Karatas OF, Ozturk S, et al. miR-145-5p suppresses cell proliferation by targeting IGF1R and NRAS genes in multiple myeloma cells. Turk J Biochem. 2023;48(5):563-9. doi:10.1515/tjb-2023-0042.
  • Chava S, Reynolds CP, Pathania AS, Gorantla S, Poluektova LY, Coulter DW, et al. miR-15a-5p, miR-15b-5p, and miR-16-5p inhibit tumor progression by directly targeting MYCN in neuroblastoma. Mol Oncol. 2020;14(1):180-96. doi:10.1002/1878-0261.12588.
  • Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ. 2010;17(2):215-20. doi:10.1038/cdd.2009.69.
  • Bhattacharya R, Nicoloso M, Arvizo R, Wang E, Cortez A, Rossi S, et al. MiR-15a and MiR-16 control Bmi-1 expression in ovarian cancer. Cancer Res. 2009;69(23):9090-5. doi:10.1158/0008-5472.CAN-09-2552.
  • Sueur G, Boutet A, Gotanègre M, Mansat-De Mas V, Besson A, Manenti S, et al. STAT5-dependent regulation of CDC25A by miR-16 controls proliferation and differentiation in FLT3-ITD acute myeloid leukemia. Sci Rep. 2020;10(1):1906. doi:10.1038/s41598-020-58651-x.
  • Guven DC, Ahmed J, Stephen B, Naing A. IGF-1R inhibitors in cancer: A review of available evidence and future outlook. Crit Rev Oncol Hematol. 2025;214:104809. doi:10.1016/j.critrevonc.2025.104809.
  • Wahner Hendrickson AE, Haluska P, Schneider PA, Loegering DA, Peterson KL, Attar R, et al. Expression of insulin receptor isoform A and insulin-like growth factor-1 receptor in human acute myelogenous leukemia: effect of the dual-receptor inhibitor BMS-536924 in vitro. Cancer Res. 2009;69(19):7635-43. doi:10.1158/0008-5472.CAN-09-0511.
  • Reyes-Carmona J. Insights on Bmi-1 therapeutic targeting in head and neck cancers. Oncol Res. 2025;33(2):301-7. doi:10.32604/or.2024.053764.
  • Saudy NS, Fawzy IM, Azmy E, Goda EF, Eneen A, Abdul Salam EM. BMI1 gene expression in myeloid leukemias and its impact on prognosis. Blood Cells Mol Dis. 2014;53(4):194-8. doi:10.1016/j.bcmd.2014.07.002.
  • Shen T, Huang S. The role of Cdc25A in the regulation of cell proliferation and apoptosis. Anticancer Agents Med Chem. 2012;12(6):631-9. doi:10.2174/187152012800617678.
  • Liu XM, Chen F, Zhang F, Xi HT, Zhao JZ. Knockdown of Chk1 inhibits proliferation and promotes apoptosis in mouse granulosa cells and its regulation mechanism by miR-15a and miR-16. In Vitro Cell Dev Biol Anim. 2022;58(7):579-86. doi:10.1007/s11626-022-00705-7.
  • Lovat F, Nigita G, Distefano R, Nakamura T, Gasparini P, Tomasello L, et al. Combined loss of function of two different loci of miR-15/16 drives the pathogenesis of acute myeloid leukemia. Proc Natl Acad Sci U S A. 2020;117(22):12332-40.10.1073/pnas.2003597117.
There are 45 citations in total.

Details

Primary Language English
Subjects Cancer Cell Biology
Journal Section Research Article
Authors

Şeyma Teomete 0000-0001-9896-7970

Murat Kaya 0000-0003-2241-7088

Ilknur Suer 0000-0003-1954-4190

Kıvanç Çefle 0000-0002-9420-4543

Şükrü Palanduz 0000-0002-9435-009X

Şükrü Öztürk 0000-0002-8809-7462

Project Number 37138
Submission Date November 11, 2025
Acceptance Date April 20, 2026
Publication Date April 25, 2026
DOI https://doi.org/10.18678/dtfd.1822082
IZ https://izlik.org/JA53SE93KB
Published in Issue Year 2026 Volume: 28 Issue: 1

Cite

APA Teomete, Ş., Kaya, M., Suer, I., Çefle, K., Palanduz, Ş., & Öztürk, Ş. (2026). Regulatory Role of miR-15a-5p and miR-16-5p in Suppressing Acute Myeloid Leukemia Cell Growth through Target Gene Interaction. Duzce Medical Journal, 28(1), 84-92. https://doi.org/10.18678/dtfd.1822082
AMA 1.Teomete Ş, Kaya M, Suer I, Çefle K, Palanduz Ş, Öztürk Ş. Regulatory Role of miR-15a-5p and miR-16-5p in Suppressing Acute Myeloid Leukemia Cell Growth through Target Gene Interaction. Duzce Med J. 2026;28(1):84-92. doi:10.18678/dtfd.1822082
Chicago Teomete, Şeyma, Murat Kaya, Ilknur Suer, Kıvanç Çefle, Şükrü Palanduz, and Şükrü Öztürk. 2026. “Regulatory Role of MiR-15a-5p and MiR-16-5p in Suppressing Acute Myeloid Leukemia Cell Growth through Target Gene Interaction”. Duzce Medical Journal 28 (1): 84-92. https://doi.org/10.18678/dtfd.1822082.
EndNote Teomete Ş, Kaya M, Suer I, Çefle K, Palanduz Ş, Öztürk Ş (April 1, 2026) Regulatory Role of miR-15a-5p and miR-16-5p in Suppressing Acute Myeloid Leukemia Cell Growth through Target Gene Interaction. Duzce Medical Journal 28 1 84–92.
IEEE [1]Ş. Teomete, M. Kaya, I. Suer, K. Çefle, Ş. Palanduz, and Ş. Öztürk, “Regulatory Role of miR-15a-5p and miR-16-5p in Suppressing Acute Myeloid Leukemia Cell Growth through Target Gene Interaction”, Duzce Med J, vol. 28, no. 1, pp. 84–92, Apr. 2026, doi: 10.18678/dtfd.1822082.
ISNAD Teomete, Şeyma - Kaya, Murat - Suer, Ilknur - Çefle, Kıvanç - Palanduz, Şükrü - Öztürk, Şükrü. “Regulatory Role of MiR-15a-5p and MiR-16-5p in Suppressing Acute Myeloid Leukemia Cell Growth through Target Gene Interaction”. Duzce Medical Journal 28/1 (April 1, 2026): 84-92. https://doi.org/10.18678/dtfd.1822082.
JAMA 1.Teomete Ş, Kaya M, Suer I, Çefle K, Palanduz Ş, Öztürk Ş. Regulatory Role of miR-15a-5p and miR-16-5p in Suppressing Acute Myeloid Leukemia Cell Growth through Target Gene Interaction. Duzce Med J. 2026;28:84–92.
MLA Teomete, Şeyma, et al. “Regulatory Role of MiR-15a-5p and MiR-16-5p in Suppressing Acute Myeloid Leukemia Cell Growth through Target Gene Interaction”. Duzce Medical Journal, vol. 28, no. 1, Apr. 2026, pp. 84-92, doi:10.18678/dtfd.1822082.
Vancouver 1.Şeyma Teomete, Murat Kaya, Ilknur Suer, Kıvanç Çefle, Şükrü Palanduz, Şükrü Öztürk. Regulatory Role of miR-15a-5p and miR-16-5p in Suppressing Acute Myeloid Leukemia Cell Growth through Target Gene Interaction. Duzce Med J. 2026 Apr. 1;28(1):84-92. doi:10.18678/dtfd.1822082