Original Article

The Expression Levels of Circulating miR-129 and miR-203a in Association with Breast Cancer and Related Metastasis

Abstract

Background: A significant part of deaths related to breast cancer is the result of invasion to other organs. It is essential to discover new non-invasive biomarkers to improve anticipation of recurrence risk in breast cancer patients. In this study, the plasma levels of miR-129 and miR-203a were evaluated to investigate their diagnostic potential in breast cancer and its metastasis.

Methods: In this case-control study, conducted in Tarbiat Modares University, Tehran, Iran, in 2019, Invasive Ductal Carcinoma blood samples were divided into 3 groups based on their stages as I, II/III, IV. Each group contained 30 individuals. We also recruited 30 normal individuals as a control group. Real-Time PCR was conducted to evaluate miR-129 and miR-203a expression levels. The discriminatory ability of the evaluated plasma miRNAs was assessed by ROC (Receiver Operating Characteristic) curves in breast cancer diagnosis and its metastasis.

Results: MiR-129 and miR-203a expression levels were significantly downregulated in breast cancer. Reducing tendency was observed in the mentioned miRNAs from less to more invasive stages. The expression level of miR-129 was decreased in metastatic than non-metastatic patients and it was significantly related to metastasis. A significant association between miR-129 expression level and lymph node status was also observed (P=0.04). Evaluation of ROC curves revealed that miR-129 and miR-203a were able to discriminate breast cancer fairly and poorly respectively. The ability of miR-129 in the diagnosis of breast cancer metastasis was poor.

Conclusion: MiR-129 and miR-203a may both act as tumor suppressor miRNAs. Our results need further evidence in a large population to be confirmed as diagnostic markers. 

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011). Global cancer statistics. CA Cancer J Clin, 61(2):69-90.
2. Weigelt B, Peterse JL, van 't Veer LJ (2005). Breast cancer metastasis: markers and models. Nat Rev Cancer, 5(8):591-602.
3. Thames HD, Buchholz TA, Smith CD (1999). Frequency of first metastatic events in breast cancer: implications for sequencing of systemic and local-regional treatment. J Clin Oncol, 17(9):2649-58.
4. Bedard PL, Hansen AR, Ratain MJ, Siu LL (2013). Tumour heterogeneity in the clinic. Nature, 501(7467):355-64.
5. Papadaki C, Stratigos M, Markakis G, et al (2018). Circulating microRNAs in the early prediction of disease recurrence in primary breast cancer. Breast Cancer Res, 20(1):72.
6. Inns J, James V (2015). Circulating microRNAs for the prediction of metastasis in breast cancer patients diagnosed with early-stage disease. Breast, 24(4):364-9.
7. Chim SS, Shing TK, Hung EC, et al (2008). Detection and characterization of placental microRNAs in maternal plasma. Clin Chem, 54(3):482-90.
8. Hamam R, Hamam D, Alsaleh KA, et al (2017). Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers. Cell Death Dis, 8(9):e3045.
9. Schwarzenbach H, Nishida N, Calin GA, Pantel K (2014). Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol, 11(3):145-56.
10. Mitchell PS, Parkin RK, Kroh EM, et al (2008). Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A, 105(30):10513-8.
11. Turchinovich A, Weiz L, Langheinz A, Burwinkel B (2011). Characterization of extracellular circulating microRNA. Nucleic Acids Res, 39(16):7223-33.
12. Dyrskjøt L, Ostenfeld MS, Bramsen JB, et al (2009). Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro. Cancer Res, 69(11):4851-60.
13. Yu Y, Zhao Y, Sun XH, et al (2015). Down-regulation of miR-129-5p via the Twist1-Snail feedback loop stimulates the epithelial-mesenchymal transition and is associated with poor prognosis in breast cancer. Oncotarget, 6(33):34423-36.
14. Tsai KW, Wu CW, Hu LY, et al (2011). Epigenetic regulation of miR‐34b and miR‐129 expression in gastric cancer. Int J Cancer, 129(11):2600-10.
15. Gao Y, Feng B, Han S, et al (2016). MicroRNA-129 in Human Cancers: from Tumorigenesis to Clinical Treatment. Cell Physiol Biochem, 39(6):2186-202.
16. Kang HS, Kim J, Jang SG, et al (2014). MicroRNA signature for HER2-positive breast and gastric cancer. Anticancer Res, 34(7):3807-10.
17. Zhang J, Li S, Yan Q, et al (2013). Interferon-beta induced microRNA-129-5p down-regulates HPV-18 E6 and E7 viral gene expression by targeting SP1 in cervical cancer cells. PloS One, 8(12):e81366.
18. Kang M, Li Y, Liu W, et al (2013). MiR-129-2 suppresses proliferation and migration of esophageal carcinoma cells through downregulation of SOX4 expression. Int J Mol Med, 32(1):51-8.
19. Xiao G, Li X, Li G, et al (2017). MiR-129 blocks estrogen induction of NOTCH signaling activity in breast cancer stem-like cells. Oncotarget, 8(61):103261-73.
20. He S, Zhang G, Dong H, Ma M, Sun Q (2016). MiR-203 facilitates tumor growth and metastasis by targeting fibroblast growth factor 2 in breast cancer. Onco Targets Ther, 9:6203.
21. Liu S, Feng P (2015). MiR-203 determines poor outcome and suppresses tumor growth by targeting TBK1 in osteosarcoma. Cell Physiol Biochem, 37(5):1956-66.
22. He JH, Li YM, Li YG, et al (2013). Hsa-miR-203 enhances the sensitivity of leukemia cells to arsenic trioxide. Exp Ther Med, 5(5):1315-21.
23. Zhang F, Yang Z, Cao M, et al (2014). MiR-203 suppresses tumor growth and invasion and down-regulates MiR-21 expression through repressing Ran in esophageal cancer. Cancer Lett, 342(1):121-9.
24. Furuta M, Kozaki KI, Tanaka S, Arii S, Imoto I, Inazawa J (2010). MiR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis, 31(5):766-76.
25. Taube JH, Malouf GG, Lu E, et al. Epigenetic silencing of microRNA-203 is required for EMT and cancer stem cell properties (2013). Sci Rep, 3:2687.
26. Tang R, Zhong T, Dang Y, Zhang X, Li P, Chen G (2016). Association between downexpression of MiR-203 and poor prognosis in non-small cell lung cancer patients. Clin Transl Oncol, 18(4):360-8.
27. Zhang Z, Zhang B, Li W, et al (2011). Epigenetic Silencing of miR-203 Upregulates SNAI2 and Contributes to the Invasiveness of Malignant Breast Cancer Cells. Genes Cancer, 2(8):782-91.
28. Zhao S, Han J, Zheng L, Yang Z, Zhao L, Lv Y (2015). MicroRNA-203 Regulates Growth and Metastasis of Breast Cancer. Cell Physiol Biochem, 37(1):35-42.
29. Meng R, Fang J, Yu Y, et al (2018). MiR-129-5p suppresses breast cancer proliferation by targeting CBX4. Neoplasma, 65(4):572-8.
30. Edge S BD, Compton C, Fritz A, Greene F, Trotti A (2009). AJCC Cancer Staging Manual. Springer.
31. Luan QX, Zhang BG, Li XJ, Guo MY (2016). MiR-129-5p is downregulated in breast cancer cells partly due to promoter H3K27m3 modification and regulates epithelial-mesenchymal transition and multi-drug resistance. Eur Rev Med Pharmacol Sci, 20(20):4257-65.
Files
IssueVol 51 No 12 (2022) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v51i12.11472
Keywords
Breast cancer Metastasis Circulating biomarkers Mirn129 microRNA Human

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Ghalkhani E, Akbari MT, Izadi P, Mahmoodzadeh H, Kamali F. The Expression Levels of Circulating miR-129 and miR-203a in Association with Breast Cancer and Related Metastasis. Iran J Public Health. 2022;51(12):2808-2816.