MicroRNA-206 as a Novel Potential Prognostic Biomarker for Distinguishing Philadelphia Chromosome-Positive and Negative ALL Patients
-
Zahra Mohammadi
,
Mehdi Allahbakhshian Farsani
,
Mohammad Javad Mousavi
,
Leila Tahmasbi
,
Narges Obeidi
,
Seyed Amin Mohammadi
,
Raziyeh Jalakani
,
Gholamreza Khamisipour
Abstract
Background: MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein-coding gene expression, and alterations in their expression are associated with leukemic transformation of hematopoietic cells. This study analyzed bone marrow samples from Philadelphia chromosome-positive (Ph+) and Philadelphia chromosome-negative (Ph−) acute lymphoblastic leukemia (ALL) patients to assess miR-320a and miR-206 expression and their relationship with prognosis.
Materials and Methods: miR-206 and miR-320a expression levels were assessed using real-time PCR in 50 bone marrow specimens: 10 from healthy individuals (control group), 20 from Ph+ ALL patients, and 20 from Ph− ALL patients. Data were analyzed using GraphPad Prism version 7, one-way ANOVA, and Chi-square tests.
Results: The Ph− ALL group exhibited a significant 3.8-fold reduction in miR-206 expression (P = 0.004), while the Ph+ ALL group showed a significant 5.34-fold increase (P = 0.006) compared to the control group. No statistically significant differences were observed in miR-320a expression between the Ph+ and Ph− groups relative to controls (P = 0.496 and P = 0.645, respectively). Data analysis revealed no association between age, sex, and miRNA expression.
Conclusion: MiR-206 showed differential expression, being significantly upregulated in Ph+ ALL and downregulated in Ph− ALL patients. This miRNA may serve as a potential diagnostic biomarker for distinguishing between the two ALL subgroups. However, further studies incorporating clinical outcome data are needed to confirm its prognostic value.
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14. Otmani K, Rouas R, Lewalle P. OncomiRs as noncoding RNAs having functions in cancer: Their role in immune suppression and clinical implications. Front Immunol. 2022;13:913951.
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17. Jiang X, Liu Y, Zhang G, et al. Aloe-Emodin Induces Breast Tumor Cell Apoptosis through Upregulation of miR-15a/miR-16-1 That Suppresses BCL2. Evid Based Complement Alternat Med. 2020 ;2020:5108298.
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21. Samaeekia R, Adorno-Cruz V, Bockhorn J, et al. miR-206 Inhibits Stemness and Metastasis of Breast Cancer by Targeting MKL1/IL11 Pathway. Clin Cancer Res. 2017 ;23(4):1091-1103.
22. Xie F, Yuan Y , Xie L, et al. miRNA-320a inhibits tumor proliferation and invasion by targeting c-Myc in human hepatocellular carcinoma. Onco Targets Ther. 2017 ; 10:885-894.
23. Shu S, Liu X, Xu M, et al. MicroRNA-320a acts as a tumor suppressor in endometrial carcinoma by targeting IGF-1R. Int J Mol Med. 2019 ;43(3):1505-1512.
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26. Siniscalco D, Galderisi U, Peluso G, et al. Circulating microRNAs in Cancer: A 5-Year Update with a Focus on Breast and Lung Cancers. Int J Mol Sci. 2024;25(6):3140.
27. Liu H, Wu H, Qin X. MicroRNA-206 serves as a tumor suppressor in pediatric acute myeloid leukemia by targeting Cyclin D1. Pathol Res Pract. 2019 ;215(10):152554.
28. Wang N, Feng T, Liu X, et al. Curcumin inhibits migration and invasion of non-small cell lung cancer cells through up-regulation of miR-206 and suppression of PI3K/AKT/mTOR signaling pathway. Acta Pharm. 2020;70(3):399-409.
29. Zheng Y, Yang X, Wang C, et al. HDAC6, modulated by miR-206, promotes endometrial cancer progression through the PTEN/AKT/mTOR pathway. Sci Rep. 2020;10(1):3576.
30. Moghbeli M. PI3K/AKT pathway as a pivotal regulator of epithelial-mesenchymal transition in lung tumor cells. Cancer Cell Int. 2024;24(1):165.
31. Wei S, Lu C, Mo S, et al. Silencing of KIF2C enhances the sensitivity of hepatocellular carcinoma cells to cisplatin through regulating the PI3K/AKT/MAPK signaling pathway. Anticancer Drugs. 2024;35(3):237-250.
32. Babaeenezhad E, Abdolvahabi Z, Asgharzadeh S, et al. Potential function of microRNA miRNA-206 in breast cancer pathogenesis: Mechanistic aspects and clinical implications. Pathol Res Pract. 2024;260:155454.
33. Sukhija S, Purohit P, Pareek P, et al. Circulating miRNA-21 Levels in Breast Cancer Patients Before and After Chemotherapy and Its Association with Clinical Improvement. Indian J Clin Biochem. 2024 ;39(2):214-220.
34. Liu L, Shi Y, Zhang P, et al. Integration analysis of miRNA-mRNA expression exploring their potential roles in intrahepatic cholangiocarcinoma. Sci Rep. 2023;13(1):8362.
35. Lei T, Zhu Y, Jiang C, et al. MicroRNA-320 was downregulated in non-small cell lung cancer and inhibited cell proliferation, migration and invasion by targeting fatty acid synthase. Mol Med Rep. 2016 ;14(2):1255-62.
36. Karabulut S, Şen S, Soydinç HO, et al. Investigation of the potential of miRNA candidates as non-invasive biomarkers for the diagnosis and follow-up of colorectal cancer. Pathol Res Pract. 2024; 254: 155094.
37. Goto Y, Kojima S, Nishikawa R, et al. MicroRNA expression signature of castration-resistant prostate cancer: the microRNA-221/222 cluster functions as a tumour suppressor and disease progression marker. Br J Cancer. 2015 ;113(7):1055-65.
38. Bereimipour A, Karimi S, Faranoush M, et al. Identification of miR-20a as A Potential Discerning Biomarker for Non-Invasive versus Invasive Retinoblastoma. Cell J. 2024;26(4):250-258.
39. Organista-Nava J, Gómez-Gómez Y, Illades-Aguiar B, et al. Regulation of the miRNA expression by TEL/AML1, BCR/ABL, MLL/AF4 and TCF3/PBX1 oncoproteins in acute lymphoblastic leukemia (Review). Oncol Rep. 2016 ;36(3):1226-32.
40. Xishan Z, Ziying L, Jing D, et al. Retraction Note: MicroRNA-320a acts as a tumor suppressor by targeting BCR/ABL oncogene in chronic myeloid leukemia. Sci Rep. 2023 ;13(1):3571.
2. Stratmann S, Yones SA, Mayrhofer M, et al. Genomic characterization of relapsed acute myeloid leukemia reveals novel putative therapeutic targets. Blood Adv. 2021; 9;5(3):900-912.
3. Malard F, Mohty M. Acute lymphoblastic leukaemia. Lancet.2020; 4;10230(395):1146-1162.
4. Jabbour E, Short NJ, Jain N, et al. Hyper-CVAD and sequential blinatumomab for newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: a single-arm, single-centre, phase 2 trial. Lancet Haematol. 2022; 9(12):e878-e885.
5. Nowell P, Hungerford D. A minute chromosome chromosome in human chronic granulocytic leukemia. Science.1984; 142: 1497.
6. Li S, Ilaria RL Jr, Million RP, et al. The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity. J Exp Med. 1999; 189(9):1399-412.
7. Komorowski L, Fidyt K, Patkowska E, et al. Philadelphia Chromosome-Positive Leukemia in the Lymphoid Lineage-Similarities and Differences with the Myeloid Lineage and Specific Vulnerabilities. Int J Mol Sci. 2020; 21(16):5776.
8. Nachi M, Kihel I, Entasoltane B, et al. Impact of the Major BCR-ABL1 Transcript Type on Clinical and Biological Parameters and Molecular Response in Patients With Chronic Myeloid Leukemia. Hematol Oncol Stem Cell Ther 2022;15(2):58-62.
9. Kang ZJ, Liu YF, Xu LZ, et al. The Philadelphia chromosome in leukemogenesis. Chin J Cancer. 2016;35:48.
10. Badar T, Alkhateeb H, Aljurf M, et al. Management of Philadelphia chromosome positive acute lymphoblastic leukemia in the current era. Curr Res Transl Med. 2023;71(2):103392.
11. Kraszewska MD, Dawidowska M, Szczepański T, et al. T‐cell acute lymphoblastic leukaemia: recent molecular biology findings. Br J Haematol. 2012 ;156(3):303-15.
12. Hirsch E, Chiarle R. Calming down T cell acute leukemia. Cancer Cell. 2012; 21(4): 449-450.
13. Fang-Fang Z, You Y, Wen-Jun L. Progress in research on childhood T-cell acute lymphocytic leukemia, Notch1 signaling pathway, and its inhibitors: A review. Bosn J Basic Med Sci. 2021;21(2):136-144.
14. Otmani K, Rouas R, Lewalle P. OncomiRs as noncoding RNAs having functions in cancer: Their role in immune suppression and clinical implications. Front Immunol. 2022;13:913951.
15. Annese T, Tamma R, De Giorgis M, et al. microRNAs Biogenesis, Functions and Role in Tumor Angiogenesis. Front Oncol. 2020;10:581007.
16. Fernando TR, Rodriguez-Malave NI, Rao DS. MicroRNAs in B cell development and malignancy. J Hematol Oncol. 2012;5:7.
17. Jiang X, Liu Y, Zhang G, et al. Aloe-Emodin Induces Breast Tumor Cell Apoptosis through Upregulation of miR-15a/miR-16-1 That Suppresses BCL2. Evid Based Complement Alternat Med. 2020 ;2020:5108298.
18. Havelange V, Garzon R. MicroRNAs: emerging key regulators of hematopoiesis. Am J Hematol. 2010; 85(12):935-42.
19. He Y, Chevillet JR, Liu G, et al. The effects of microRNA on the absorption, distribution, metabolism and excretion of drugs. Br J Pharmacol. 2015 ;172(11):2733-47.
20. Zhang WL, Lv W, Sun SZ, et al. miR-206 inhibits metastasis-relevant traits by degrading MRTF-A in anaplastic thyroid cancer. Int J Oncol. 2015 ;47(1):133-42.
21. Samaeekia R, Adorno-Cruz V, Bockhorn J, et al. miR-206 Inhibits Stemness and Metastasis of Breast Cancer by Targeting MKL1/IL11 Pathway. Clin Cancer Res. 2017 ;23(4):1091-1103.
22. Xie F, Yuan Y , Xie L, et al. miRNA-320a inhibits tumor proliferation and invasion by targeting c-Myc in human hepatocellular carcinoma. Onco Targets Ther. 2017 ; 10:885-894.
23. Shu S, Liu X, Xu M, et al. MicroRNA-320a acts as a tumor suppressor in endometrial carcinoma by targeting IGF-1R. Int J Mol Med. 2019 ;43(3):1505-1512.
24. Kasinski AL, Slack FJ. Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 2011;11(12):849-64.
25. Svoronos AA, Engelman DM, Slack FJ. OncomiR or Tumor Suppressor? The Duplicity of MicroRNAs in Cancer. Cancer Res. 2016;76(13):3666-70.
26. Siniscalco D, Galderisi U, Peluso G, et al. Circulating microRNAs in Cancer: A 5-Year Update with a Focus on Breast and Lung Cancers. Int J Mol Sci. 2024;25(6):3140.
27. Liu H, Wu H, Qin X. MicroRNA-206 serves as a tumor suppressor in pediatric acute myeloid leukemia by targeting Cyclin D1. Pathol Res Pract. 2019 ;215(10):152554.
28. Wang N, Feng T, Liu X, et al. Curcumin inhibits migration and invasion of non-small cell lung cancer cells through up-regulation of miR-206 and suppression of PI3K/AKT/mTOR signaling pathway. Acta Pharm. 2020;70(3):399-409.
29. Zheng Y, Yang X, Wang C, et al. HDAC6, modulated by miR-206, promotes endometrial cancer progression through the PTEN/AKT/mTOR pathway. Sci Rep. 2020;10(1):3576.
30. Moghbeli M. PI3K/AKT pathway as a pivotal regulator of epithelial-mesenchymal transition in lung tumor cells. Cancer Cell Int. 2024;24(1):165.
31. Wei S, Lu C, Mo S, et al. Silencing of KIF2C enhances the sensitivity of hepatocellular carcinoma cells to cisplatin through regulating the PI3K/AKT/MAPK signaling pathway. Anticancer Drugs. 2024;35(3):237-250.
32. Babaeenezhad E, Abdolvahabi Z, Asgharzadeh S, et al. Potential function of microRNA miRNA-206 in breast cancer pathogenesis: Mechanistic aspects and clinical implications. Pathol Res Pract. 2024;260:155454.
33. Sukhija S, Purohit P, Pareek P, et al. Circulating miRNA-21 Levels in Breast Cancer Patients Before and After Chemotherapy and Its Association with Clinical Improvement. Indian J Clin Biochem. 2024 ;39(2):214-220.
34. Liu L, Shi Y, Zhang P, et al. Integration analysis of miRNA-mRNA expression exploring their potential roles in intrahepatic cholangiocarcinoma. Sci Rep. 2023;13(1):8362.
35. Lei T, Zhu Y, Jiang C, et al. MicroRNA-320 was downregulated in non-small cell lung cancer and inhibited cell proliferation, migration and invasion by targeting fatty acid synthase. Mol Med Rep. 2016 ;14(2):1255-62.
36. Karabulut S, Şen S, Soydinç HO, et al. Investigation of the potential of miRNA candidates as non-invasive biomarkers for the diagnosis and follow-up of colorectal cancer. Pathol Res Pract. 2024; 254: 155094.
37. Goto Y, Kojima S, Nishikawa R, et al. MicroRNA expression signature of castration-resistant prostate cancer: the microRNA-221/222 cluster functions as a tumour suppressor and disease progression marker. Br J Cancer. 2015 ;113(7):1055-65.
38. Bereimipour A, Karimi S, Faranoush M, et al. Identification of miR-20a as A Potential Discerning Biomarker for Non-Invasive versus Invasive Retinoblastoma. Cell J. 2024;26(4):250-258.
39. Organista-Nava J, Gómez-Gómez Y, Illades-Aguiar B, et al. Regulation of the miRNA expression by TEL/AML1, BCR/ABL, MLL/AF4 and TCF3/PBX1 oncoproteins in acute lymphoblastic leukemia (Review). Oncol Rep. 2016 ;36(3):1226-32.
40. Xishan Z, Ziying L, Jing D, et al. Retraction Note: MicroRNA-320a acts as a tumor suppressor by targeting BCR/ABL oncogene in chronic myeloid leukemia. Sci Rep. 2023 ;13(1):3571.
| Files | ||
| Issue | Vol 20 No 2 (2026) | |
| Section | Original Article(s) | |
| Keywords | ||
| Micro-RNA; Acute lymphoblastic leukemia (ALL); MiR-206; MiR-320a; Philadelphia chromosome; Biomarker | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Mohammadi Z, Allahbakhshian Farsani M, Mousavi MJ, Tahmasbi L, Obeidi N, Mohammadi SA, Jalakani R, Khamisipour G. MicroRNA-206 as a Novel Potential Prognostic Biomarker for Distinguishing Philadelphia Chromosome-Positive and Negative ALL Patients. Int J Hematol Oncol Stem Cell Res. 2026;20(2):135-143.
