Exploring the miR-19a/PTEN Interaction: Insights into Tumor Biology and Treatment Strategies
DOI:
https://doi.org/10.62382/jcbt.v2i3.66Keywords:
miR-19a, PTEN, Cancer progression, Tumor microenvironment, Therapy resistanceAbstract
MicroRNAs (miRNAs) play a crucial function in the complex regulatory networks that control cancer progression. Among them, miR-19a has become a significant oncogenic player, especially via its engagement with the tumor suppressor phosphatase and tensin homolog (PTEN), leading to aberrant activation of the PI3K/AKT signaling cascade. This review critically examines the mechanistic underpinnings of the miR-19a/PTEN axis, highlighting its impact on tumor formation and spread and therapy resistance across various malignancies. This explores the practical consequences in a clinical context of miR-19a as a possible biomarker for cancer prognosis and its modulation as a treatment approach. Furthermore, this review discusses the interplay among miR-19a and other molecular regulators within the tumor microenvironment, shedding light on new avenues for targeted interventions. Given the mounting evidence linking miR-19a dysregulation to aggressive cancer phenotypes, understanding its intricate regulatory framework landscape could pave the way for novel therapeutic breakthroughs.
Downloads
References
Nunes S, Bastos R, Marinho AI, Vieira R, Benício I, et al. Recent advances in the development and clinical application of miRNAs in infectious diseases. Non-coding RNA Research. 2025, 10, 41-54. DOI: 10.1016/j.ncrna.2024.09.005
O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Frontiers in Endocrinology. 2018, 9, 402. DOI: 10.3389/fendo.2018.00402
Touchaei AZ, Vahidi S, Samadani AA. Decoding the interaction between miR-19a and CBX7 focusing on the implications for tumor suppression in cancer therapy. Medical Oncology. 2023, 41(1), 21. DOI: 10.1007/s12032-023-02251-y
Ardizzone A, Calabrese G, Campolo M, Filippone A, Giuffrida D, et al. Role of miRNA-19a in Cancer Diagnosis and Poor Prognosis. International Journal of Molecular Sciences. 2021, 22(9). DOI: 10.3390/ijms22094697
Ashraf NS, Mahjabeen I, Hussain MZ, Rizwan M, Arshad M, et al. Role of exosomal miRNA-19a/19b and PTEN in brain tumor diagnosis. Future Oncology. 2023, 19(22), 1563-1576. DOI: 10.2217/fon-2023-0234
Zhang Y, Liu XX, Zhang JY, Xu YY, Shao J, et al. Inhibition of miR-19a partially reversed the resistance of colorectal cancer to oxaliplatin via PTEN/PI3K/AKT pathway. Aging (Albany NY). 2020, 12(7), 5640-5650. DOI: 10.18632/aging.102929
Causin RL, Polezi MR, Freitas AJA, Calfa S, Altei WF, et al. EV-miRNAs from breast cancer patients of plasma as potential prognostic biomarkers of disease recurrence. Heliyon. 2024, 10(14), e33933. DOI: 10.1016/j.heliyon.2024.e33933
Gong QY, Luo DW, Wang HY, Xu X, Fan Y, et al. Inhibiting autophagy by miR-19a-3p/PTEN regulation protected retinal pigment epithelial cells from hyperglycemic damage. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2023, 1870(7), 119530. DOI: 10.1016/j.bbamcr.2023.119530
Yan YQ, Gao Y, Kumar G, Fang QL, Yan HL, et al. Exosomal MicroRNAs modulate the cognitive function in fasudil treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice model of Alzheimer's disease. Metabolic Brain Disease. 2024, 39(7), 1335-51. DOI: 10.1007/s11011-024-01395-8
Fusco N, Sajjadi E, Venetis K, Gaudioso G, Lopez G, et al. PTEN alterations and their role in cancer management: are we making headway on precision medicine? Genes. 2020, 11(7), 719. DOI: 10.3390/genes11070719
Zhang GF, Zhong JM, Lin L, Liu ZH. MiR-19 enhances pancreatic cancer progression by targeting PTEN through PI3K/AKT signaling pathway. European Review for Medical and Pharmacological Sciences. 2020, 24(3), 1098-1107. DOI: 10.26355/eurrev_202002_20160
Dou L, Meng XY, Sui XF, Wang SY, Shen T, et al. MiR-19a regulates PTEN expression to mediate glycogen synthesis in hepatocytes. Scientific Reports. 2015, 5(1), 11602. DOI: 10.1038/srep11602
Bergez-Hernández F, Irigoyen-Arredondo M, Martínez-Camberos A. A systematic review of mechanisms of PTEN gene down-regulation mediated by miRNA in prostate cancer. Heliyon. 2024, 10(15), e34950. DOI: 10.1016/j.heliyon.2024.e34950
Tang YC, Weng XH, Liu C, Li X, Chen C. Hypoxia Enhances Activity and Malignant Behaviors of Colorectal Cancer Cells through the STAT3/MicroRNA-19a/PTEN/PI3K/AKT Axis. Analytical Cellular Pathology (Amsterdam). 2021, 2021, 4132488. DOI: 10.1155/2021/4132488
Chakrabortty A, Patton DJ, Smith BF, Agarwal P. miRNAs: Potential as Biomarkers and Therapeutic Targets for Cancer. Genes (Basel). 2023, 14(7), 1375. DOI: 10.3390/genes14071375
Zhang X, Chen Y, Zhao P, Zang L, Zhang Z, et al. MicroRNA-19a functions as an oncogene by regulating PTEN/AKT/pAKT pathway in myeloma. Leuk Lymphoma. 2017;58(4):932-40. doi:10.1080/10428194.2016.1213827.
Taipaleenmäki H, Saito H, Schröder S, Maeda M, Mettler R, et al. Antagonizing microRNA-19a/b augments PTH anabolic action and restores bone mass in osteoporosis in mice. EMBO Molecular Medicine. 2022, 14(11), e13617. DOI: 10.15252/emmm.202013617
Condrat CE, Thompson DC, Barbu MG, Bugnar OL, Boboc A, et al. miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis. Cells. 2020, 9(2), 276. DOI: 10.3390/cells9020276
Haddadi N, Lin Y, Travis G, Simpson AM, Nassif NT, et al. PTEN/PTENP1: 'Regulating the regulator of RTK-dependent PI3K/Akt signalling', new targets for cancer therapy. Molecular Cancer. 2018, 17(1), 37. DOI: 10.1186/s12943-018-0803-3
Turnham DJ, Bullock N, Dass MS, Staffurth JN, Pearson HB. The PTEN Conundrum: How to Target PTEN-Deficient Prostate Cancer. Cells. 2020, 9(11), 2342. DOI: 10.3390/cells9112342
Gkountakos A, Sartori G, Falcone I, Piro G, Ciuffreda L, et al. PTEN in Lung Cancer: Dealing with the Problem, Building on New Knowledge and Turning the Game Around. Cancers (Basel). 2019, 11(8), 1141. DOI: 10.3390/cancers11081141
Jia ZF, Wang K, Zhang AL, Wang GX, Kang CS, et al. miR-19a and miR-19b overexpression in gliomas. Pathology & Oncology Research. 2013, 19(4), 847-53. DOI: 10.1007/s12253-013-9653-x
Qin N, Tong GF, Sun LW, Xu XL. Long Noncoding RNA MEG3 Suppresses Glioma Cell Proliferation, Migration, and Invasion by Acting as a Competing Endogenous RNA of miR-19a. Oncology Research. 2017, 25(9), 1471-1478. DOI: 10.3727/096504017x14886689179993
Zhao D, Chen YB, Chen SL, Zheng CY, Hu J, et al. MiR-19a regulates the cell growth and apoptosis of osteosarcoma stem cells by targeting PTEN. Tumour Biology. 2017, 39(5), 1010428317705341. DOI: 10.1177/1010428317705341
Luo TT, Zhou XC, Jiang EH, Wang L, Ji YT, et al. Osteosarcoma Cell-Derived Small Extracellular Vesicles Enhance Osteoclastogenesis and Bone Resorption Through Transferring MicroRNA-19a-3p. Frontiers in Oncology. 2021, 11, 618662. DOI: 10.3389/fonc.2021.618662
Li X, Sun XH, Xu HY, Pan HS, Liu Y, et al. Circ_ORC2 enhances the regulatory effect of miR-19a on its target gene PTEN to affect osteosarcoma cell growth. Biochemical and Biophysical Research Communications. 2019, 514(4), 1172-8. DOI: 10.1016/j.bbrc.2019.04.188
Li XW, Yan X, Wang F, Yang Q, Luo X, et al. Down-regulated lncRNA SLC25A5-AS1 facilitates cell growth and inhibits apoptosis via miR-19a-3p/PTEN/PI3K/AKT signalling pathway in gastric cancer. Journal of Cellular and Molecular Medicine. 2019, 23(4), 2920-2932. DOI: 10.1111/jcmm.14200
Feng YG, Liu J, Kang YM, He Y, Liang B, et al. miR-19a acts as an oncogenic microRNA and is up-regulated in bladder cancer. Journal of Experimental & Clinical Cancer Research. 2014, 33(1), 67. DOI: 10.1186/preaccept-9242556491295527
Calderaro J, Rebouissou S, de Koning L, Masmoudi A, Hérault A, et al. PI3K/AKT pathway activation in bladder carcinogenesis. International Journal of Cancer. 2014, 134(8), 1776-84. DOI: 10.1002/ijc.28518
Ma Q, Peng ZQ, Wang L, Li YM, Wang KZ, et al. miR-19a correlates with poor prognosis of clear cell renal cell carcinoma patients via promoting cell proliferation and suppressing PTEN/SMAD4 expression. International Journal of Oncology. 2016, 49(6), 2589-2599. DOI: 10.3892/ijo.2016.3746
Wang YH, Zhao SZ, Zhu LH, Zhang QL, Ren YF. MiR-19a negatively regulated the expression of PTEN and promoted the growth of ovarian cancer cells. Gene. 2018, 670, 166-173. DOI: 10.1016/j.gene.2018.05.063
Li J, Yang S, Yan W, Yang J, Qin YJ, et al. MicroRNA-19 triggers epithelial-mesenchymal transition of lung cancer cells accompanied by growth inhibition. Laboratory Investigation. 2015, 95(9), 1056-70. DOI: 10.1038/labinvest.2015.76
Hosseini SA, Seidi M, Yaghoobi H. Designed miR-19a/b sponge induces apoptosis in lung cancer cells through the PI3K-PTEN-Akt pathway regulation. Molecular Biology Reports. 2022, 49(9), 8485-8493. DOI: 10.1007/s11033-022-07670-0
Jiang XM, Yu XN, Liu TT, Zhu HR, Shi X, et al. microRNA-19a-3p promotes tumor metastasis and chemoresistance through the PTEN/Akt pathway in hepatocellular carcinoma. Biomedicine & Pharmacotherapy. 2018, 105, 1147-1154. DOI: 10.1016/j.biopha.2018.06.097
Park MN, Um ES, Rahman MA, Kim JW, Park SS, et al. Leonurus japonicus Houttuyn induces reactive oxygen species-mediated apoptosis via regulation of miR-19a-3p/PTEN/PI3K/AKT in U937 and THP-1 cells. Journal of Ethnopharmacology. 2022, 291, 115129. DOI: 10.1016/j.jep.2022.115129
Wang F, Li T, Zhang B, Li H, Wu Q, et al. MicroRNA-19a/b regulates multidrug resistance in human gastric cancer cells by targeting PTEN. Biochemical and Biophysical Research Communications. 2013, 434(3), 688-94. DOI: 10.1016/j.bbrc.2013.04.010
Tavakoli Pirzaman A, Ebrahimzadeh Pirshahid M, Babajani B, Rahmati A, Niknezhad S, et al. The Role of microRNAs in Regulating Cancer Cell Response to Oxaliplatin-Containing Regimens. Technology in Cancer Research & Treatment. 2023, 22, 15330338231206003. DOI: 10.1177/15330338231206003
Ye CY, Lin QB, Zheng CP. Overexpressed RBPMS-AS1 increased cell radiosensitivity by sponging miR-19a-3p in lung cancer cell lines (A549 and SK-MES-1) via regulating PTEN/AKT axis. International Journal of Radiation Biology. 2023, 99(9), 1352-1363. DOI: 10.1080/09553002.2023.2181997
Mao JT, Xue BY, Smoake J, Lu QY, Park H, et al. MicroRNA-19a/b mediates grape seed procyanidin extract-induced anti-neoplastic effects against lung cancer. The Journal of Nutritional Biochemistry. 2016, 34, 118-25. DOI: 10.1016/j.jnutbio.2016.05.003
Zhang B, Liu Y, Zhang JN. Silencing of miR-19a-3p enhances osteosarcoma cells chemosensitivity by elevating the expression of tumor suppressor PTEN. Oncology Letters. 2019, 17(1), 414-421. DOI: 10.3892/ol.2018.9592
Xing SJ, Qu Y, Li CY, Huang A, Tong S, et al. Deregulation of lncRNA-AC078883.3 and microRNA-19a is involved in the development of chemoresistance to cisplatin via modulating signaling pathway of PTEN/AKT. Journal of Cellular Physiology. 2019, 234(12), 22657-65. DOI: 10.1002/jcp.28832
Wu JS, Jiang Y, Cao WS, Li XT, Xie CF, et al. miR-19 targeting of PTEN mediates butyl benzyl phthalate-induced proliferation in both ER(+) and ER(-) breast cancer cells. Toxicology Letters. 2018, 295, 124-133. DOI: 10.1016/j.toxlet.2018.05.040
Cao WS, Lu XM, Zhong CY, Wu JS. Sulforaphane Suppresses MCF-7 Breast Cancer Cells Growth via miR-19/PTEN Axis to Antagonize the Effect of Butyl Benzyl Phthalate. Nutrition and Cancer. 2023, 75(3), 980-991. DOI: 10.1080/01635581.2022.2156555
Li XT, Xie W, Xie CF, Huang C, Zhu JY, et al. Curcumin modulates miR-19/PTEN/AKT/p53 axis to suppress bisphenol A-induced MCF-7 breast cancer cell proliferation. Phytotherapy Research. 2014, 28(10), 1553-60. DOI: 10.1002/ptr.5167
Lee S, Lee H, Bae H, Choi EH, Kim SJ. Epigenetic silencing of miR-19a-3p by cold atmospheric plasma contributes to proliferation inhibition of the MCF-7 breast cancer cell. Scientific Reports. 2016, 6, 30005. DOI: 10.1038/srep30005
Qian YY, Liu ZS, Zhang Z, Levenson AS, Li K. Pterostilbene increases PTEN expression through the targeted downregulation of microRNA-19a in hepatocellular carcinoma. Molecular Medicine Reports. 2018, 17(4), 5193-5201. DOI: 10.3892/mmr.2018.8515
Kazemi A, Abroun S, Soleimani M. AntagomiR-19a Induced Better Responsiveness to Bortezomib in Myeloma Cell Lines. Cell Journal. 2021, 23(5):503-509. DOI: 10.22074/cellj.2021.7302
Cao Y, Yu SL, Wang Y, Guo GY, Ding Q, et al. MicroRNA-dependent regulation of PTEN after arsenic trioxide treatment in bladder cancer cell line T24. Tumour Biology. 2011, 32(1), 179-88. DOI: 10.1007/s13277-010-0111-z
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Sogand Vahidi
This work is licensed under a Creative Commons Attribution 4.0 International License.
