Research Article
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MiR-7-5p May Inhibit AML Cell Proliferation Via SKP2, KLF4, OGT Target Genes

Year 2025, Volume: 15 Issue: 1, 8 - 14
https://doi.org/10.33808/clinexphealthsci.1279724

Abstract

Objective: Acute Myeloid Leukemia (AML) is distinguished by the differentiation and overgrowth of blast cells. In the current study, we purposed to elucidate the effect of miR-7-5p on AML cellular processes and the expression level of potential target genes.
Methods: miR-7-5p mimic was transfected into AML cells by lipofectamine-mediated method and verified by qRT-PCR. The miR-7-5p's effect on proliferation and apoptosis was investigated by WST-8 and Caspase-3 kit (respectively). miRDB, miRTarBase, Targetscan, miRWalk, https://ongene.bioinfo-minzhao.org/, and http://soft.bioinfo-minzhao.org/lgl/a databases were utilized for in silico identification of possible target genes of miR-7-5p. Relative gene expression of potential target genes was investigated via the qRT-PCR technique.
Results: In the group that is transfected with miR-7-5p, proliferation significantly decreased and apoptosis increased as against the control group. BCL2, SKP2, OGT, KLF4 and EGFR gene expression levels, which were determined as a result of possible target gene analysis by in silico methods and literature search, were investigated in AML cell lines. While the SKP2, KLF4 and OGT expression levels were statistically decreased in the group of transfected with mimic miR-7-5p, no statistically significant change was detected in the expressions of BCL2 and EGFR genes.
Conclusion: miR-7-5p may affect the cancer process in AML by targeting SKP2, KLF4, and OGT genes. It is very important to identify and validate the miR-7-5p target genes, which has the possibility to be a new biomarker in the early diagnosis and therapy of AML. Therefore, our data obtained at mRNA level should be confirmed by further studies.

Ethical Statement

Ethical approval was not obtained as a commercially produced cell line was used in the study.

Supporting Institution

Istanbul University Scientific Research Projects Unit

Project Number

37653

Thanks

The authors thank Istanbul University Scientific Research Projects Unit for their project support (Project no: 37653).

References

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  • Capik O, Sanli F, Kurt A, Ceylan O, Suer I, Kaya M, Ittmann M, Karatas OF. CASC11 promotes aggressiveness of prostate cancer cells through miR-145/IGF1R axis. Prostate Cancer Prostatic Dis. 2021;24(3):891-902. https://doi.org/10.1038/s41391-021-00353-0.
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  • Tang Y, Tang Z, Yang J, Liu T, Tang Y. MicroRNA-7-5p Inhibits Migration, Invasion and Metastasis of Intrahepatic Cholangiocarcinoma by Inhibiting MyD88. J Clin Transl Hepatol. 2021;9(6):809-17. https://doi.org/10.14218/JCTH.2021.00021.
  • Gstaiger M, Jordan R, Lim M, Catzavelos C, Mestan J, Slingerland J, Krek W. Skp2 is oncogenic and overexpressed in human cancers. Proc Natl Acad Sci U S A. 2001;98(9):5043-8. https://doi.org/10.1073/pnas.081474898.
  • Wang HF, Dong ZY, Yan L, Yang S, Xu HN, Chen SL, Wang WR, Yang QL, Chen CJ. The N-terminal polypeptide derived from vMIP-II exerts its antitumor activity in human breast cancer through CXCR4/miR-7-5p/Skp2 pathway. J Cell Physiol. 2020;235(12):9474-86. https://doi.org/10.1002/jcp.29755.
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  • Noura M, Morita K, Kiyose H, Matsuo H, Nishinaka-Arai Y, Kurokawa M, Kamikubo Y, Adachi S. Pivotal role of DPYSL2A in KLF4-mediated monocytic differentiation of acute myeloid leukemia cells. Sci Rep. 2020;10(1):20245. https://doi.org/10.1038/s41598-020-76951-0.
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  • He N, Ma D, Tan Y, Liu M. Upregulation of O-GlcNAc transferase is involved in the pathogenesis of acute myeloid leukemia. Asia Pac J Clin Oncol. 2022;18(5):e318-e28. https://doi.org/10.1111/ajco.13685.
  • Suer I, Kaya M, Ozgur E. The Effect of miR-34a-5p and miR-145-5p Ectopic Expression on Cell Proliferation and Target Gene Expression in the MDA-MB-231 Cell Line. NKMJ. 2021;9(2):166-73. https://doi.org/10.4274/nkmj.galenos.2021.770512.
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Year 2025, Volume: 15 Issue: 1, 8 - 14
https://doi.org/10.33808/clinexphealthsci.1279724

Abstract

Project Number

37653

References

  • Short NJ, Ravandi F. How close are we to incorporating measurable residual disease into clinical practice for acute myeloid leukemia? Haematologica. 2019;104(8):1532-41. https://doi.org/10.3324/haematol.2018.208454
  • Vakiti A, Mewawalla P. Acute Myeloid Leukemia. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC.; 2023.
  • Kaya M, Suer I. The effect of miR-34a-5p on overexpressed AML associated genes. J Ist Faculty Med. 2023;86(1):59-68. https://doi.org/10.26650/IUITFD.1168793
  • Suer I, Guzel E, Karatas OF, Creighton CJ, Ittmann M, Ozen M. MicroRNAs as prognostic markers in prostate cancer. Prostate. 2019;79(3):265-71. https://doi.org/10.1002/pros.23731.
  • Suer I, Kaya M. Is the AURKB Gene Involved in Aml Cell Proliferation Since It is Targeted by miR-34a-5p and let-7b-5p? Konuralp Medical Journal. 2023. DOI:10.18521/ktd.1171549.
  • Kaya M, Karatas OF. The Relationship Between Larynx Cancer and MicroRNAs. Van Med J 2020;27(4):535-41. https://doi.org/10.5505/vtd.2020.80947.
  • Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19(1):92-105. https://doi.org/10.1101/gr.082701.108
  • Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215-33. https://doi.org/10.1016/j.cell.2009.01.002.
  • Kalinowski FC, Brown RA, Ganda C, Giles KM, Epis MR, Horsham J, Leedman PJ. microRNA-7: a tumor suppressor miRNA with therapeutic potential. Int J Biochem Cell Biol. 2014;54:312-7. https://doi.org/10.1016/j.biocel.2014.05.040.
  • Gu DN, Jiang MJ, Mei Z, Dai JJ, Dai CY, Fang C, Huang Q, Tian L. microRNA-7 impairs autophagy-derived pools of glucose to suppress pancreatic cancer progression. Cancer Lett. 2017;400:69-78. https://doi.org/10.1016/j.canlet.2017.04.020.
  • Zhu W, Wang Y, Zhang D, Yu X, Leng X. MiR-7-5p functions as a tumor suppressor by targeting SOX18 in pancreatic ductal adenocarcinoma. Biochem Biophys Res Commun. 2018;497(4):963-70. https://doi.org/10.1016/j.bbrc.2018.02.005.
  • Zeng CY, Zhan YS, Huang J, Chen YX. MicroRNA‑7 suppresses human colon cancer invasion and proliferation by targeting the expression of focal adhesion kinase. Mol Med Rep. 2016;13(2):1297-303. https://doi.org/10.3892/mmr.2015.4643.
  • Giles KM, Brown RA, Epis MR, Kalinowski FC, Leedman PJ. miRNA-7-5p inhibits melanoma cell migration and invasion. Biochem Biophys Res Commun. 2013;430(2):706-10. https://doi.org/10.1016/j.bbrc.2012.11.086.
  • Xiao H. MiR-7-5p suppresses tumor metastasis of non-small cell lung cancer by targeting NOVA2. Cell Mol Biol Lett. 2019;24:60. https://doi.org/10.1186/s11658-019-0188-3.
  • Shi Y, Luo X, Li P, Tan J, Wang X, Xiang T, Ren G. miR-7-5p suppresses cell proliferation and induces apoptosis of breast cancer cells mainly by targeting REGγ. Cancer Lett. 2015;358(1):27-36. https://doi.org/10.1016/j.canlet.2014.12.014.
  • Yang Z, Shi X, Li C, Wang X, Hou K, Li Z, Zhang X, Fan Y, Qu X, Che X, Liu Y. Long non-coding RNA UCA1 upregulation promotes the migration of hypoxia-resistant gastric cancer cells through the miR-7-5p/EGFR axis. Exp Cell Res. 2018;368(2):194-201. https://doi.org/10.1016/j.yexcr.2018.04.030.
  • Liu Z, Liu Y, Li L, Xu Z, Bi B, Wang Y, Li JY. MiR-7-5p is frequently downregulated in glioblastoma microvasculature and inhibits vascular endothelial cell proliferation by targeting RAF1. Tumour Biol. 2014;35(10):10177-84. https://doi.org/10.1007/s13277-014-2318-x.
  • Sorrentino D, Frentzel J, Mitou G, Blasco RB, Torossian A, Hoareau-Aveilla C, Pighi C, Farcé M, Meggetto F, Manenti S, Espinos E, Chiarle R, Giuriato S. High Levels of miR-7-5p Potentiate Crizotinib-Induced Cytokilling and Autophagic Flux by Targeting RAF1 in NPM-ALK Positive Lymphoma Cells. Cancers (Basel). 2020;12(10). https://doi.org/10.3390/cancers12102951.
  • Jiang D, Wu X, Sun X, Tan W, Dai X, Xie Y, Du A, Zhao Q. Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11. J Nanobiotechnology. 2022;20(1):29. https://doi.org/10.1186/s12951-021-01206-7.
  • Pelcovits A, Niroula R. Acute Myeloid Leukemia: A Review. R I Med J (2013). 2020;103(3):38-40.
  • Testa U, Pelosi E. MicroRNAs expressed in hematopoietic stem/progenitor cells are deregulated in acute myeloid leukemias. Leuk Lymphoma. 2015;56(5):1466-74. https://doi.org/10.3109/10428194.2014.955019.
  • Capik O, Sanli F, Kurt A, Ceylan O, Suer I, Kaya M, Ittmann M, Karatas OF. CASC11 promotes aggressiveness of prostate cancer cells through miR-145/IGF1R axis. Prostate Cancer Prostatic Dis. 2021;24(3):891-902. https://doi.org/10.1038/s41391-021-00353-0.
  • Nair R, Salinas-Illarena A, Baldauf HM. New strategies to treat AML: novel insights into AML survival pathways and combination therapies. Leukemia. 2021;35(2):299-311. https://doi.org/10.1038/s41375-020-01069-1.
  • Liu Y, Cheng Z, Pang Y, Cui L, Qian T, Quan L, Zhao H, Shi J, Ke X, Fu L. Role of microRNAs, circRNAs and long noncoding RNAs in acute myeloid leukemia. J Hematol Oncol. 2019;12(1):51. https://doi.org/10.1186/s13045-019-0734-5.
  • Li Q, Wu X, Guo L, Shi J, Li J. MicroRNA-7-5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non-small cell lung cancer. FEBS Open Bio. 2019;9(11):1983-93. https://doi.org/10.1002/2211-5463.12738.
  • Tang Y, Tang Z, Yang J, Liu T, Tang Y. MicroRNA-7-5p Inhibits Migration, Invasion and Metastasis of Intrahepatic Cholangiocarcinoma by Inhibiting MyD88. J Clin Transl Hepatol. 2021;9(6):809-17. https://doi.org/10.14218/JCTH.2021.00021.
  • Gstaiger M, Jordan R, Lim M, Catzavelos C, Mestan J, Slingerland J, Krek W. Skp2 is oncogenic and overexpressed in human cancers. Proc Natl Acad Sci U S A. 2001;98(9):5043-8. https://doi.org/10.1073/pnas.081474898.
  • Wang HF, Dong ZY, Yan L, Yang S, Xu HN, Chen SL, Wang WR, Yang QL, Chen CJ. The N-terminal polypeptide derived from vMIP-II exerts its antitumor activity in human breast cancer through CXCR4/miR-7-5p/Skp2 pathway. J Cell Physiol. 2020;235(12):9474-86. https://doi.org/10.1002/jcp.29755.
  • Dan W, Zhong L, Zhang Z, Wan P, Lu Y, Wang X, Liu Z, Chu X, Liu B. RIP1-dependent Apoptosis and Differentiation Regulated by Skp2 and Akt/GSK3β in Acute Myeloid Leukemia. Int J Med Sci. 2022 Mar 6;19(3):525-536. https://doi.org/10.7150/ijms.68385. PMID: 35370472; PMCID: PMC8964317.
  • Thacker G, Mishra M, Sharma A, Singh AK, Sanyal S, Trivedi AK. CDK2-instigates C/EBPα degradation through SKP2 in Acute myeloid leukemia. Med Oncol. 2021 May 17;38(6):69. https://doi.org/10.1007/s12032-021-01523-9. PMID: 34002296.
  • Thacker G, Mishra M, Sharma A, Singh AK, Sanyal S, Trivedi AK. E3 ligase SCFSKP2 ubiquitinates and degrades tumor suppressor C/EBPα in acute myeloid leukemia, Life Sciences (2020), https://doi.org/10.1016/j.lfs.2020.118041.
  • Min YH, Cheong JW, Lee MH, Kim JY, Lee ST, Hahn JS, Ko YW. Elevated S-phase kinase-associated protein 2 protein expression in acute myelogenous leukemia: its association with constitutive phosphorylation of phosphatase and tensin homologue protein and poor prognosis. Clin Cancer Res. 2004 Aug 1;10(15):5123-30. https://doi.org/10.1158/1078-0432.CCR-04-0136. PMID: 15297415
  • Dong M, Xie Y, Xu Y. miR-7-5p regulates the proliferation and migration of colorectal cancer cells by negatively regulating the expression of Krüppel-like factor 4. Oncol Lett. 2019;17(3):3241-6. https://doi.org/10.3892/ol.2019.10001.
  • Noura M, Morita K, Kiyose H, Matsuo H, Nishinaka-Arai Y, Kurokawa M, Kamikubo Y, Adachi S. Pivotal role of DPYSL2A in KLF4-mediated monocytic differentiation of acute myeloid leukemia cells. Sci Rep. 2020;10(1):20245. https://doi.org/10.1038/s41598-020-76951-0.
  • Fardini Y, Dehennaut V, Lefebvre T, Issad T. O-GlcNAcylation: A New Cancer Hallmark? Front Endocrinol (Lausanne). 2013;4:99. https://doi.org/10.3389/fendo.2013.00099.
  • Krause MW, Love DC, Ghosh SK, Wang P, Yun S, Fukushige T, Hanover JA. Nutrient-Driven O-GlcNAcylation at Promoters Impacts Genome-Wide RNA Pol II Distribution. Front Endocrinol (Lausanne). 2018;9:521. https://doi.org/10.3389/fendo.2018.00521.
  • Slawson C, Hart GW. O-GlcNAc signalling: implications for cancer cell biology. Nat Rev Cancer. 2011;11(9):678-84. https://doi.org/10.1038/nrc3114.
  • Asthana A, Ramakrishnan P, Vicioso Y, Zhang K, Parameswaran R. Hexosamine Biosynthetic Pathway Inhibition Leads to AML Cell Differentiation and Cell Death. Mol Cancer Ther. 2018;17(10):2226-37. https://doi.org/10.1158/1535-7163.MCT-18-0426.
  • He N, Ma D, Tan Y, Liu M. Upregulation of O-GlcNAc transferase is involved in the pathogenesis of acute myeloid leukemia. Asia Pac J Clin Oncol. 2022;18(5):e318-e28. https://doi.org/10.1111/ajco.13685.
  • Suer I, Kaya M, Ozgur E. The Effect of miR-34a-5p and miR-145-5p Ectopic Expression on Cell Proliferation and Target Gene Expression in the MDA-MB-231 Cell Line. NKMJ. 2021;9(2):166-73. https://doi.org/10.4274/nkmj.galenos.2021.770512.
  • Mahmud H, Kornblau SM, Ter Elst A, Scherpen FJ, Qiu YH, Coombes KR, de Bont ES. Epidermal growth factor receptor is expressed and active in a subset of acute myeloid leukemia. J Hematol Oncol. 2016 Aug 3;9(1):64. https://doi.org/10.1186/s13045-016-0294-x. PMID: 27488458; PMCID: PMC4971659
  • Wei Y, Cao Y, Sun R, Cheng L, Xiong X, Jin X, He X, Lu W, Zhao M. Targeting Bcl-2 Proteins in Acute Myeloid Leukemia. Front Oncol. 2020 Nov 5;10:584974. https://doi.org/10.3389/fonc.2020.584974. PMID: 33251145; PMCID: PMC7674767
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There are 47 citations in total.

Details

Primary Language English
Subjects Medical Genetics (Excl. Cancer Genetics)
Journal Section Articles
Authors

Ezgi Mehteroğlu 0000-0001-7478-7625

Ilknur Suer 0000-0003-1954-4190

Murat Kaya 0000-0003-2241-7088

Şükrü Öztürk 0000-0002-8809-7462

Kıvanç Çefle 0000-0002-9420-4543

Şükrü Palanduz 0000-0002-9435-009X

Project Number 37653
Early Pub Date March 23, 2025
Publication Date
Submission Date April 14, 2023
Published in Issue Year 2025 Volume: 15 Issue: 1

Cite

APA Mehteroğlu, E., Suer, I., Kaya, M., Öztürk, Ş., et al. (2025). MiR-7-5p May Inhibit AML Cell Proliferation Via SKP2, KLF4, OGT Target Genes. Clinical and Experimental Health Sciences, 15(1), 8-14. https://doi.org/10.33808/clinexphealthsci.1279724
AMA Mehteroğlu E, Suer I, Kaya M, Öztürk Ş, Çefle K, Palanduz Ş. MiR-7-5p May Inhibit AML Cell Proliferation Via SKP2, KLF4, OGT Target Genes. Clinical and Experimental Health Sciences. March 2025;15(1):8-14. doi:10.33808/clinexphealthsci.1279724
Chicago Mehteroğlu, Ezgi, Ilknur Suer, Murat Kaya, Şükrü Öztürk, Kıvanç Çefle, and Şükrü Palanduz. “MiR-7-5p May Inhibit AML Cell Proliferation Via SKP2, KLF4, OGT Target Genes”. Clinical and Experimental Health Sciences 15, no. 1 (March 2025): 8-14. https://doi.org/10.33808/clinexphealthsci.1279724.
EndNote Mehteroğlu E, Suer I, Kaya M, Öztürk Ş, Çefle K, Palanduz Ş (March 1, 2025) MiR-7-5p May Inhibit AML Cell Proliferation Via SKP2, KLF4, OGT Target Genes. Clinical and Experimental Health Sciences 15 1 8–14.
IEEE E. Mehteroğlu, I. Suer, M. Kaya, Ş. Öztürk, K. Çefle, and Ş. Palanduz, “MiR-7-5p May Inhibit AML Cell Proliferation Via SKP2, KLF4, OGT Target Genes”, Clinical and Experimental Health Sciences, vol. 15, no. 1, pp. 8–14, 2025, doi: 10.33808/clinexphealthsci.1279724.
ISNAD Mehteroğlu, Ezgi et al. “MiR-7-5p May Inhibit AML Cell Proliferation Via SKP2, KLF4, OGT Target Genes”. Clinical and Experimental Health Sciences 15/1 (March 2025), 8-14. https://doi.org/10.33808/clinexphealthsci.1279724.
JAMA Mehteroğlu E, Suer I, Kaya M, Öztürk Ş, Çefle K, Palanduz Ş. MiR-7-5p May Inhibit AML Cell Proliferation Via SKP2, KLF4, OGT Target Genes. Clinical and Experimental Health Sciences. 2025;15:8–14.
MLA Mehteroğlu, Ezgi et al. “MiR-7-5p May Inhibit AML Cell Proliferation Via SKP2, KLF4, OGT Target Genes”. Clinical and Experimental Health Sciences, vol. 15, no. 1, 2025, pp. 8-14, doi:10.33808/clinexphealthsci.1279724.
Vancouver Mehteroğlu E, Suer I, Kaya M, Öztürk Ş, Çefle K, Palanduz Ş. MiR-7-5p May Inhibit AML Cell Proliferation Via SKP2, KLF4, OGT Target Genes. Clinical and Experimental Health Sciences. 2025;15(1):8-14.

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