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image of miR-34 as a Critical Regulator in Ovarian Cancer

Abstract

Ovarian cancer (OC) is a gynecologic disease characterized by the uncontrolled growth and proliferation of abnormal cells in the ovaries, fallopian tubes, or peritoneum. Emerging evidence has shown the pivotal role of non-coding RNAs (ncRNAs), such as miRNAs, in driving the pathogenesis of OC. miRNAs are recognized as small ncRNAs that play critical roles in regulating gene expression in normal development and in disease states, including OC. Among miRNAs, the expression of miR-34a was found to be downregulated in OC. Elevated levels of this miRNA are associated with the induction of apoptosis and the inhibition of OC cell proliferation by targeting various signaling pathways, including NOTCH1, P21/P53, STAT3, and BCL2 in OC. Therefore, miR-34a can be a therapeutic target in the management of OC. In this review, we summarized the functional significance of this miRNA in the treatment of OC.

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2025-01-03
2025-06-29
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References

  1. Anghel B. Georgescu M.T. Serboiu C.S. Marinescu A.N. Aliuș C. Georgescu D.E. Mocanu B. Sucuri S. Stanescu A.D. Optimizing Palliative Pelvic Radiotherapy in Gynecological Cancers: A Systematic Review and Analysis. Diagnostics (Basel) 2024 14 5 547 10.3390/diagnostics14050547 38473019
    [Google Scholar]
  2. Pour F.K. Keivan M. Ghaedrahmati F. Saadati N. Moramezi F. Nikbakht R. Farzaneh M. Endometrial Cancer Stem Cells Related Signaling Pathways. Curr. Cancer Ther. Rev. 2023 19 4 284 291 10.2174/1573394719666230306145642
    [Google Scholar]
  3. Pfeifer C.R. Hales K.H. Hales D.B. Shyer A.E. Rodrigues A.R. Collective fibroblast mechanics in ovarian cancer metastasis. Biophys. J. 2024 123 3 405a 10.1016/j.bpj.2023.11.2486
    [Google Scholar]
  4. Sowamber R. Lukey A. Huntsman D. Hanley G. Ovarian cancer: From precursor lesion identification to population-based prevention programs. Curr. Oncol. 2023 30 12 10179 10194 10.3390/curroncol30120741 38132375
    [Google Scholar]
  5. O’Mahony D.G. Ramus S.J. Southey M.C. Meagher N.S. Hadjisavvas A. John E.M. Hamann U. Imyanitov E.N. Andrulis I.L. Sharma P. Daly M.B. Hake C.R. Weitzel J.N. Jakubowska A. Godwin A.K. Arason A. Bane A. Simard J. Soucy P. Caligo M.A. Mai P.L. Claes K.B.M. Teixeira M.R. Chung W.K. Lazaro C. Hulick P.J. Toland A.E. Pedersen I.S. Mourits M.J.E. Neuhausen S.L. Vega A. de la Hoya M. Nevanlinna H. Dhawan M. Zampiga V. Danesi R. Varesco L. Gismondi V. Vellone V.G. James P.A. Janavicius R. Nikitina-Zake L. Nielsen F.C. van Overeem Hansen T. Pejovic T. Borg A. Rantala J. Offit K. Montagna M. Nathanson K.L. Domchek S.M. Osorio A. García M.J. Karlan B.Y. Lesueur F. De Fazio A. Bowtell D. De Fazio A. McGuffog L. Leslie G. Parsons M.T. Dörk T. Speith L-M. dos Santos E.S. da Costa A.A.B.A. Radice P. Peterlongo P. Papi L. Engel C. Hahnen E. Schmutzler R.K. Wappenschmidt B. Easton D.F. Tischkowitz M. Singer C.F. Tan Y.Y. Whittemore A.S. Sieh W. Brenton J.D. Yannoukakos D. Fostira F. Konstantopoulou I. Soukupova J. Vocka M. Chenevix-Trench G. Pharoah P.D.P. Antoniou A.C. Goldgar D.E. Spurdle A.B. Michailidou K. de la Hoya M. van Overeem Hansen T. dos Santos E.S. Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2. Br. J. Cancer 2023 128 12 2283 2294 10.1038/s41416‑023‑02263‑5 37076566
    [Google Scholar]
  6. Lashen A. Algethami M. Alqahtani S. Shoqafi A. Sheha A. Jeyapalan J.N. Mongan N.P. Rakha E.A. Madhusudan S. The Clinicopathological Significance of the Cyclin D1/E1–Cyclin-Dependent Kinase (CDK2/4/6)–Retinoblastoma (RB1/pRB1) Pathway in Epithelial Ovarian Cancers. Int. J. Mol. Sci. 2024 25 7 4060 10.3390/ijms25074060 38612869
    [Google Scholar]
  7. K A.R. Arumugam S. Muninathan N. Baskar K. S D. D D.R. P53 Gene as a Promising Biomarker and Potential Target for the Early Diagnosis of Reproductive Cancers. Cureus 2024 16 5 e60125 10.7759/cureus.60125 38864057
    [Google Scholar]
  8. Tcyganov E.N. Kwak T. Yang X. Poli A.N.R. Hart C. Bhuniya A. Targeting LxCxE cleft pocket of retinoblastoma protein in M2 macrophages inhibits ovarian cancer progression. bioRxiv 2024 2024 593562 10.1101/2024.05.10.593562
    [Google Scholar]
  9. C e D.K. C V.T.T. J C E.M. G W M L.E. Irene H. Mariette G. J T V.G.R. Willem V. D L.K. J M B.F. M e B.A. The Impact of BRCA1- and BRCA2 Mutations on Ovarian Reserve Status. Reprod. Sci. 2023 30 1 270 282 10.1007/s43032‑022‑00997‑w 35705781
    [Google Scholar]
  10. Ehmann T. Barel S. Ray A. Borsch D. The Role of Estrogen in Ovarian Cancer and the Pathways by Which Estrogen Acts. 2023 Available from: https://www.hmsreview.org/issue-8/ehmann-2023
  11. Kim S.Y. Chang H.K. Kwon O. Park J. Myong J-P. Asbestos exposure and Ovarian Cancer; A meta-analysis. Saf. Health Work 2023 38496274
    [Google Scholar]
  12. Wentzensen N. O’Brien K.M. Talc, body powder, and ovarian cancer: A summary of the epidemiologic evidence. Gynecol. Oncol. 2021 163 1 199 208 10.1016/j.ygyno.2021.07.032 34366148
    [Google Scholar]
  13. Harris B.H.L. Macaulay V.M. Harris D.A. Klenerman P. Karpe F. Lord S.R. Harris A.L. Buffa F.M. Obesity: a perfect storm for carcinogenesis. Cancer Metastasis Rev. 2022 41 3 491 515 10.1007/s10555‑022‑10046‑2 36038791
    [Google Scholar]
  14. Cui J. Wang Y. Premature ovarian insufficiency: a review on the role of tobacco smoke, its clinical harm, and treatment. J. Ovarian Res. 2024 17 1 8 10.1186/s13048‑023‑01330‑y 38191456
    [Google Scholar]
  15. Evangelinakis N. Geladari E.V. Geladari C.V. Kontogeorgi A. Papaioannou G.K. Peppa M. Kalantaridou S. The influence of environmental factors on premature ovarian insufficiency and ovarian aging. Maturitas 2024 179 107871 10.1016/j.maturitas.2023.107871 37925867
    [Google Scholar]
  16. Chiaffarino F. Cipriani S. Ricci E. Esposito G. Parazzini F. Vercellini P. Histologic Subtypes in Endometriosis-Associated Ovarian Cancer and Ovarian Cancer Arising in Endometriosis: A Systematic Review and Meta-Analysis. Reprod. Sci. 2024 ••• 1 9
    [Google Scholar]
  17. Hassan S. Thacharodi A. Priya A. Meenatchi R. Hegde T.A. R T. Nguyen H.T. Pugazhendhi A. Endocrine disruptors: Unravelling the link between chemical exposure and Women’s reproductive health. Environ. Res. 2024 241 117385 10.1016/j.envres.2023.117385 37838203
    [Google Scholar]
  18. Veneziani A.C. Gonzalez-Ochoa E. Alqaisi H. Madariaga A. Bhat G. Rouzbahman M. Sneha S. Oza A.M. Heterogeneity and treatment landscape of ovarian carcinoma. Nat. Rev. Clin. Oncol. 2023 20 12 820 842 10.1038/s41571‑023‑00819‑1 37783747
    [Google Scholar]
  19. Moftakhar A. Najafi S. Anbiyaee O. Farzaneh M. Khoshnam S.E. Functional Roles of the lncRNA MALAT1 in Glioma. Curr. Cancer Ther. Rev. 2024 20 2 166 176 10.2174/1573394719666230720164009
    [Google Scholar]
  20. Najafi S. Ghaedrahmati F. Abouali Gale Dari M. Farzaneh M. Mohammad Jafari R. The Regulatory Role of Circular RNAs as miRNA Sponges in Cervical Cancer. Curr. Signal Transduct. Ther. 2023 18 3 e241123223777 10.2174/0115743624273536231105142321
    [Google Scholar]
  21. Li S. Wei X. He J. Cao Q. Du D. Zhan X. Zeng Y. Yuan S. Sun L. The comprehensive landscape of miR-34a in cancer research. Cancer Metastasis Rev. 2021 40 3 925 948 10.1007/s10555‑021‑09973‑3 33959850
    [Google Scholar]
  22. Dirimtekin E. Mortoglou M. Alavanda C. Benomar Yemlahi A. Arslan Ates E. Guney I. Uysal-Onganer P. miR-34a-FOXP1 Loop in Ovarian Cancer. ACS Omega 2023 8 30 27743 27750 10.1021/acsomega.3c03867 37546627
    [Google Scholar]
  23. Welponer H. Tsibulak I. Wieser V. Degasper C. Shivalingaiah G. Wenzel S. Sprung S. Marth C. Hackl H. Fiegl H. Zeimet A.G. The miR-34 family and its clinical significance in ovarian cancer. J. Cancer 2020 11 6 1446 1456 10.7150/jca.33831 32047551
    [Google Scholar]
  24. Abdelaal A.M. Sohal I.S. Iyer S. Sudarshan K. Kothandaraman H. Lanman N.A. Low P.S. Kasinski A.L. A first-in-class fully modified version of miR-34a with outstanding stability, activity, and anti-tumor efficacy. Oncogene 2023 42 40 2985 2999 10.1038/s41388‑023‑02801‑8 37666938
    [Google Scholar]
  25. Veltri A.J. D’Orazio K.N. Lessen L.N. Loll-Krippleber R. Brown G.W. Green R. Distinct elongation stalls during translation are linked with distinct pathways for mRNA degradation. eLife 2022 11 e76038 10.7554/eLife.76038 35894211
    [Google Scholar]
  26. del Valle-Morales D. Le P. Saviana M. Romano G. Nigita G. Nana-Sinkam P. Acunzo M. The epitranscriptome in miRNAs: crosstalk, detection, and function in cancer. Genes (Basel) 2022 13 7 1289 10.3390/genes13071289 35886072
    [Google Scholar]
  27. McGeary S.E. Bisaria N. Pham T.M. Wang P.Y. Bartel D.P. MicroRNA 3′-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position. eLife 2022 11 e69803 10.7554/eLife.69803 35191832
    [Google Scholar]
  28. Rokavec M. Huang Z. Hermeking H. Meta-analysis of miR-34 target mRNAs using an integrative online application. Comput. Struct. Biotechnol. J. 2023 21 267 274 10.1016/j.csbj.2022.12.003 36582442
    [Google Scholar]
  29. Di Paolo D. Pastorino F. Brignole C. Corrias M.V. Emionite L. Cilli M. Tamma R. Priddy L. Amaro A. Ferrari D. Marotta R. Ferretti E. Pfeffer U. Ribatti D. Sementa A.R. Brown D. Ikegaki N. Shimada H. Ponzoni M. Perri P. Combined replenishment of miR‐34a and let‐7b by targeted nanoparticles inhibits tumor growth in neuroblastoma preclinical models. Small 2020 16 20 1906426 10.1002/smll.201906426 32323486
    [Google Scholar]
  30. Choi YJ Lin C-P Risso D Chen S Kim TA Tan MH Deficiency of microRNA miR-34a expands cell fate potential in pluripotent stem cells. Science. 2017 355 6325 eaag1927 10.1126/science.aag1927
    [Google Scholar]
  31. Min X. Wang J.Y. Zong F.J. Zhao J. Liu N. He K.W. miR-34a regulates silent synapse and synaptic plasticity in mature hippocampus. Prog. Neurobiol. 2023 222 102404 10.1016/j.pneurobio.2023.102404 36642095
    [Google Scholar]
  32. Gaderpour S. Ghiasi R. Hamidian G. Heydari H. Keyhanmanesh R. Voluntary exercise improves spermatogenesis and testicular apoptosis in type 2 diabetic rats through alteration in oxidative stress and mir-34a/SIRT1/p53 pathway. Iran. J. Basic Med. Sci. 2021 24 1 58 65 33643571
    [Google Scholar]
  33. Wang J. He P. Tian Q. Luo Y. He Y. Liu C. Gong P. Guo Y. Ye Q. Li M. Genetic modification of miR-34a enhances efficacy of transplanted human dental pulp stem cells after ischemic stroke. Neural Regen. Res. 2023 18 9 2029 2036 36926729
    [Google Scholar]
  34. Peters F. Grimm C. Regulation of ABCA1 by miR-33 and miR-34a in the Aging Eye. Retinal Degenerative Diseases XIX: Mechanisms and Experimental Therapy. Springer 2023 55 59 10.1007/978‑3‑031‑27681‑1_9
    [Google Scholar]
  35. Chen R. Chen H. Yang Z. Zhu L. Bei Y. Chen W. Qiu Y. Danlou tablet inhibits high-glucose-induced cardiomyocyte apoptosis via the miR-34a-SIRT1 axis. Heliyon 2023 9 3 e14479 10.1016/j.heliyon.2023.e14479 36950610
    [Google Scholar]
  36. Liu X. Zhao Z. Chen D. Zhang Z. Lin X. Shen Z. Lin Q. Fan K. Wang Q. Zhang W. Ou Q. SIRT1 and miR-34a-5p Expression in PBMCs as Potential Biomarkers for Patients With Type 2 Diabetes With Cognitive Impairments. J. Clin. Endocrinol. Metab. 2024 109 3 815 826 10.1210/clinem/dgad562 37758217
    [Google Scholar]
  37. Nóbrega OT Morais-Junior GS Viana NI Reis ST Perez DI Freitas WM Circulating miR-34a and Bone Mineral Density of Brazilian Very-Old Adults. J Aging Res. 2020 2020 3431828 10.1155/2020/3431828
    [Google Scholar]
  38. Briones-Espinoza M.J. Cortés-García J.D. Vega-Cárdenas M. Uresti-Rivera E.U. Gómez-Otero A. López-López N. Mejía-Torres M. Portales-Pérez D.P. Decreased levels and activity of Sirt1 are modulated by increased miR-34a expression in adipose tissue mononuclear cells from subjects with overweight and obesity: A pilot study. Diabetes Metab. Syndr. 2020 14 5 1347 1354 10.1016/j.dsx.2020.07.014 32755834
    [Google Scholar]
  39. Xu Y. Zhu Y. Hu S. Pan X. Bawa F.C. Wang H.H. Wang D.Q.H. Yin L. Zhang Y. Hepatocyte miR-34a is a key regulator in the development and progression of non-alcoholic fatty liver disease. Mol. Metab. 2021 51 101244 10.1016/j.molmet.2021.101244 33930596
    [Google Scholar]
  40. Kalfert D. Ludvikova M. Pesta M. Ludvik J. Dostalova L. Kholová I. Multifunctional Roles of miR-34a in Cancer: A Review with the Emphasis on Head and Neck Squamous Cell Carcinoma and Thyroid Cancer with Clinical Implications. Diagnostics (Basel) 2020 10 8 563 10.3390/diagnostics10080563 32764498
    [Google Scholar]
  41. Li W.J. Wang Y. Liu R. Kasinski A.L. Shen H. Slack F.J. Tang D.G. MicroRNA-34a: Potent Tumor Suppressor, Cancer Stem Cell Inhibitor, and Potential Anticancer Therapeutic. Front. Cell Dev. Biol. 2021 9 640587 10.3389/fcell.2021.640587 33763422
    [Google Scholar]
  42. Hermeking H. The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010 17 2 193 199 10.1038/cdd.2009.56 19461653
    [Google Scholar]
  43. Schmid G. Notaro S. Reimer D. Abdel-Azim S. Duggan-Peer M. Holly J. Fiegl H. Rössler J. Wiedemair A. Concin N. Altevogt P. Marth C. Zeimet A.G. Expression and promotor hypermethylation of miR-34a in the various histological subtypes of ovarian cancer. BMC Cancer 2016 16 1 102 10.1186/s12885‑016‑2135‑2 26879132
    [Google Scholar]
  44. Arapaki A. Karabelas A. Panoutsopoulou K. Papachristopoulou G. Avgeris M. Scorilas A. EP1277 Clinical evaluation of miR-34a in ovarian carcinoma. BMJ Specialist Journal 2019 10.1136/ijgc‑2019‑ESGO.1283
    [Google Scholar]
  45. Yao S. Gao M. Wang Z. Wang W. Zhan L. Wei B. Upregulation of MicroRNA-34a Sensitizes Ovarian Cancer Cells to Resveratrol by Targeting Bcl-2. Yonsei Med. J. 2021 62 8 691 701 10.3349/ymj.2021.62.8.691 34296546
    [Google Scholar]
  46. Wei B Yao S Gao M Wang Z Wang W Zhan L Resveratrol suppresses ovarian cancer cell growth and invasion through upregulation of microRNA-34a. Res Sq. 2020 2020 10.21203/rs.3.rs‑38233/v1
    [Google Scholar]
  47. Tao F. Tian X. Lu M. Zhang Z. A novel lncRNA, Lnc-OC1, promotes ovarian cancer cell proliferation and migration by sponging miR-34a and miR-34c. J. Genet. Genomics 2018 45 3 137 145 10.1016/j.jgg.2018.03.001 29576507
    [Google Scholar]
  48. Jia Y. Lin R. Jin H. Si L. Jian W. Yu Q. Yang S. RETRACTED: MicroRNA-34 suppresses proliferation of human ovarian cancer cells by triggering autophagy and apoptosis and inhibits cell invasion by targeting Notch 1. Biochimie 2019 160 193 199 10.1016/j.biochi.2019.03.011 30905732
    [Google Scholar]
  49. Maeda K. Sasaki H. Ueda S. Miyamoto S. Terada S. Konishi H. Kogata Y. Ashihara K. Fujiwara S. Tanaka Y. Tanaka T. Hayashi M. Ito Y. Kondo Y. Ochiya T. Ohmichi M. Serum exosomal microRNA-34a as a potential biomarker in epithelial ovarian cancer. J. Ovarian Res. 2020 13 1 47 10.1186/s13048‑020‑00648‑1 32336272
    [Google Scholar]
  50. Xu D. Song Q. Liu Y. Chen W. Lu L. Xu M. Fang X. Zhao W. Zhou H. LINC00665 promotes Ovarian Cancer progression through regulating the miRNA-34a-5p/E2F3 axis. J. Cancer 2021 12 6 1755 1763 10.7150/jca.51457 33613764
    [Google Scholar]
  51. Dong P. Xiong Y. Watari H. Hanley S.J.B. Konno Y. Ihira K. Yamada T. Kudo M. Yue J. Sakuragi N. MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells. J. Exp. Clin. Cancer Res. 2016 35 1 132 10.1186/s13046‑016‑0415‑y 27596137
    [Google Scholar]
  52. Jiang X. Ye Z. Jiang Y. Yu W. Fang Q. LncRNA OIP5-AS1 upregulates snail expression by sponging miR-34a to promote ovarian carcinoma cell invasion and migration. Biol. Res. 2020 53 1 49 10.1186/s40659‑020‑00315‑1 33092644
    [Google Scholar]
  53. Zuo Y. Zheng W. Liu J. Tang Q. Wang S.S. Yang X.S. MiR-34a-5p/PD-L1 axis regulates cisplatin chemoresistance of ovarian cancer cells. Neoplasma 2020 67 1 93 101 10.4149/neo_2019_190202N106 31777260
    [Google Scholar]
  54. Lv T. Song K. Zhang L. Li W. Chen Y. Diao Y. Yao Q. Liu P. miRNA-34a decreases ovarian cancer cell proliferation and chemoresistance by targeting HDAC1. Biochem. Cell Biol. 2018 96 5 663 671 10.1139/bcb‑2018‑0031 29561664
    [Google Scholar]
  55. Yokomizo R. Yanaihara N. Yamaguchi N. Saito M. Kawabata A. Takahashi K. Takenaka M. Yamada K. Shapiro J.S. Okamoto A. MicroRNA-34a /IL-6R pathway as a potential therapeutic target for ovarian high-grade serous carcinoma. Oncotarget 2019 10 47 4880 4893 10.18632/oncotarget.27117 31448054
    [Google Scholar]
  56. Robelin P. Tod M. Colomban O. Ray-Coquard I.L. De Rauglaudre G. Florence J. Chevalier A. combe P. Lortholary A. Hamizi S. Raban N. Ferron G. Meunier J. Berton-Rigaud D. Alexandre J. Kaminsky-Forrett M-C. Dubot C. Leary A. Malaurie E. You B. Comparison of 11 circulating miRNAs and CA125 kinetics in ovarian cancer during first line treatment: Data from the randomized CHIVA trial (a GINECO-GCIG study). Ann. Oncol. 2019 30 v783 v784 10.1093/annonc/mdz268.072
    [Google Scholar]
  57. Li H-L. Duan Y-A. Zhao N. MiR-34a-5p directly targeting TRIM44 affects the biological behavior of ovarian cancer cells. Eur. Rev. Med. Pharmacol. Sci. 2021 25 3 1250 1260 33629295
    [Google Scholar]
  58. Li Y. Du M. Fang J. Zhou J. Chen Z. UTMD promoted local delivery of miR-34a-mimic for ovarian cancer therapy. Drug Deliv. 2021 28 1 1616 1625 10.1080/10717544.2021.1955041 34319204
    [Google Scholar]
  59. Hashemi Sheikhshabani S. Amini-Farsani Z. Rahmati S. Jazaeri A. Mohammadi-Samani M. Asgharzade S. Oleuropein reduces cisplatin resistance in ovarian cancer by targeting apoptotic pathway regulators. Life Sci. 2021 278 119525 10.1016/j.lfs.2021.119525 33894272
    [Google Scholar]
  60. Kumar V. Pandey A. Arora A. Gautam P. Bisht D. Gupta S. Chaurasia A. Sachan M. Diagnostics and Therapeutic Potential of miR-205 and miR-34a in Ovarian Cancer Management: A miRNA-Target-Based Analysis. DNA Cell Biol. 2023 42 3 151 162 10.1089/dna.2022.0487 36779980
    [Google Scholar]
  61. Ding N. Wu H. Tao T. Peng E. NEAT1 regulates cell proliferation and apoptosis of ovarian cancer by miR-34a-5p/BCL2. OncoTargets Ther. 2017 10 4905 4915 10.2147/OTT.S142446 29062236
    [Google Scholar]
  62. Kumar V. Gupta S. Varma K. Chaurasia A. Sachan M. Diagnostic performance of microRNA-34a, let-7f and microRNA-31 in epithelial ovarian cancer prediction. J. Gynecol. Oncol. 2022 33 4 e49 10.3802/jgo.2022.33.e49 35557032
    [Google Scholar]
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  • Article Type:
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Keywords: ovarian cancer ; tumor suppressor ; therapeutic potential ; miR-34a ; biomarker
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