Evaluation of the MiR-513a-5p Impinges on Progesterone Receptor Protein Expression in Breast Cancer Cells: A Systematic Review and Meta-analysis

Document Type : Review Article


1 Department of Clinical Pharmacy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

2 School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

3 Department of ENT, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Internal Medicine, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran


Background and aim: MicroRNAs can be considered as a predictor or cause of breast cancer.  The present study was conducted to evaluate MiR-513a-5p's impacts on progesterone receptor protein expression in breast cancer cells.
Material and methods: The present study was based on the PRISMA 2020-27-item checklist.  By giving the keywords microRNAs, breast cancer, MiR-513a-5p, progesterone, all articles available in the international databases, PubMed, Web of Science, Scopus, Science Direct, Web of Knowledge, EBSCO, Wiley, ISI, Elsevier, Embase databases and Google Scholar search engine were reviewed until August 2023.  STATA/MP.  V17 software was used in this meta-analysis.
Results: Three articles were included in the present study.  MiR-513a-5p upregulation was directly and statistically significantly associated with breast cancer risk (OR = 1.45; 95% CI 1.07–1.83; P<0.01).
Conclusions: The results of the present study can affect different aspects of breast cancer development.  The use and identification of miR-513-a-5p as a long-term biomarker to identify the pathways involved in the early development of breast cancer should be considered.


Main Subjects

[1] Cable JK, Grider MH. Physiology, Progesterone. 2020.
[2] Solano ME, Arck PC. Steroids, pregnancy and fetal development. Frontiers in immunology. 2020;10:3017. https://doi.org/10.3389/fimmu.2019.03017.
[3] Haider R. Anatomy of the Breast. International Journal of Scientific Multidisciplinary Research. 2023;1(5):401-22. https://doi.org/10.55927/ijsmr.v1i5.4394.
[4] Watkins EJ. Overview of breast cancer. Journal of the American Academy of PAs. 2019;32(10):13-7. https://doi.org/10.1097/01.JAA.0000580524.95733.3d.
[5] Weaver M, Stuckey A. Benign breast disorders. Obstetrics and Gynecology Clinics. 2022;49(1):57-72. https://doi.org/10.1016/j.ogc.2021.11.003.
[6] Horwitz KB, Sartorius CA. 90 years of progesterone: progesterone and progesterone receptors in breast cancer: past, present, future. Journal of Molecular Endocrinology. 2020;65(1):T49-63. https://doi.org/10.1530/JME-20-0104.
[7] Aggelis V, Johnston SR. Advances in endocrine-based therapies for estrogen receptor-positive metastatic breast cancer. Drugs. 2019;79:1849-66. https://doi.org/10.1007/s40265-019-01208-8.
[8] Lei JT, Gou X, Seker S, Ellis MJ. ESR1 alterations and metastasis in estrogen receptor positive breast cancer. Journal of cancer metastasis and treatment. 2019;5:38. https://doi.org/10.20517/2394-4722.2019.12.
[9] Najim O, Seghers S, Sergoynne L, Van Gaver H, Papadimitriou K, Wouters K, et al. The association between type of endocrine therapy and development of estrogen receptor-1 mutation (s) in patients with hormone-sensitive advanced breast cancer: a systematic review and meta-analysis of randomized and non-randomized trials. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2019;1872(2):188315. https://doi.org/10.1016/j.bbcan.2019.188315.
[10] Giuliano M, Schettini F, Rognoni C, Milani M, Jerusalem G, Bachelot T, et al. Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis. The Lancet Oncology. 2019;20(10):1360-9. https://doi.org/10.1016/S1470-2045(19)30420-6.
[11] Allison KH, Hammond ME, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, et al. Estrogen and progesterone receptor testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists guideline update. Archives of pathology & laboratory medicine. 2020;144(5):545-63. https://doi.org/10.5858/arpa.2019-0904-SA.
[12] Scabia V, Ayyanan A, De Martino F, Agnoletto A, Battista L, Laszlo C, et al. Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor. Nature Communications. 2022;13(1):3127. https://doi.org/10.1038/s41467-022-30898-0.
[13] Gatza ML, Lucas JE, Barry WT, Kim JW, Wang Q, D. Crawford M, et al. A pathway-based classification of human breast cancer. Proceedings of the National Academy of Sciences. 2010;107(15):6994-9. https://doi.org/10.1073/pnas.0912708107.
[14] Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor?. Cancer and metastasis reviews. 2009;28:369-78. https://doi.org/10.1007/s10555-009-9188-5.
[15] Azodian Ghajar H, Koohi Ortakand R. The Promising Role of MicroRNAs, Long Non-Coding RNAs and Circular RNAs in Urological Malignancies. Translational Research in Urology. 2022;4(1):9-23. https://doi.org/10.22034/tru.2022.315706.1088.
[16] Dilsiz N. Role of exosomes and exosomal microRNAs in cancer. Future science OA. 2020;6(4):FSO465. https://doi.org/10.2144/fsoa-2019-0116.
[17] Lebron-Zapata L, Jochelson MS. Overview of breast cancer screening and diagnosis. PET clinics. 2018;13(3):301-23. https://doi.org/10.1016/j.cpet.2018.02.001.
[18] Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. International journal of surgery. 2021;88:105906. https://doi.org/10.1016/j.ijsu.2021.105906.
[19] GRADE Working Group. Grading quality of evidence and strength of recommendations. Bmj. 2004;328(7454):1490. https://doi.org/10.1136/bmj.328.7454.1490.
[20] Fu A, Yu Z, Zhang E, Song J. Long noncoding RNA ZBED3‐AS1 restrains breast cancer progression by targeting the microRNA‐513a‐5p/KLF6 axis. Thoracic cancer. 2021;12(20):2719-31. https://doi.org/10.1111/1759-7714.14111.
[21] Muti P, Donzelli S, Sacconi A, Hossain A, Ganci F, Frixa T, et al. MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer: the hOrmone and Diet in the ETiology of breast cancer prospective study. Carcinogenesis. 2018;39(2):98-108. https://doi.org/10.1093/carcin/bgx126.
[22] Cochrane DR, Jacobsen BM, Connaghan KD, Howe EN, Bain DL, Richer JK. Progestin regulated miRNAs that mediate progesterone receptor action in breast cancer. Molecular and cellular endocrinology. 2012;355(1):15-24. https://doi.org/10.1016/j.mce.2011.12.020.
[23] Lee JH, Lydon JP, Kim CH. Progesterone suppresses the m TOR pathway and promotes generation of induced regulatory T cells with increased stability. European journal of immunology. 2012;42(10):2683-96. https://doi.org/10.1002/eji.201142317.
[24] Brisken C. Reply to Is progesterone a neutral or protective factor for breast cancer?. Nature Reviews Cancer. 2014;14(2):146. https://doi.org/10.1038/nrc3518-c2.
[25] Maillot G, Lacroix-Triki M, Pierredon S, Gratadou L, Schmidt S, Bénès V, et al. Widespread estrogen-dependent repression of micrornas involved in breast tumor cell growth. Cancer research. 2009;69(21):8332-40. https://doi.org/10.1158/0008-5472.CAN-09-2206.