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Expanding the Biotherapeutics Realm via miR-34a: "Potent Clever Little" Agent in Breast Cancer Therapy
Mohsen Mohammady1,2, Seyed I Ghetmiri1,2, Mahtab Baharizade1,2
1Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran.
Background:
One of the most prevalent cancers befell to women is considered to be breast cancer (BC). It is also the deadliest among the female population after lung cancer. Additionally, several studies have demonstrated that there is an association between microRNA34-a and breast cancer.
Methods:
We searched PubMed, Web of Science, and Google Scholar up to December 2018. Those studies which have been studied miR-34a and its tumor-suppressing capabilities were considered as the most important topics. Moreover, we extracted articles which were solely focused on microRNA-34a in breast cancer therapy. Finally, 80 articles were included.
Results:
In comparison with the normal tissues, down-regulation of miR-34a expression is shown considerably in tumor cells. Overexpression of miR-34a acts as a tumor suppressor by transcriptional regulating one of the signaling pathways (TP53), NOTCH, and transforming growth factor beta (TGF-β), Bcl- 2 and SIRT1genes, HDAC1 and HDAC7, Fra-1, TPD52, TLR Via CXCL10. Moreover, drug resistance declines which lead to the apoptosis, cell cycle arrest and senescence. As a result, the proliferation, invasion and metastasis of the tumor are suppressed. The Mrx34 drug contains miR-34a mimic and a lipid vector. MiR-34a as the active ingredient portrays the role of a tumor suppressor. This drug has recently entered the clinical trials studies.
Conclusion:
These findings suggest a robust cause for developing miR-34a as a therapeutic agent to target BC. In that scenario, miR-34a is strongly useful to introduce new therapeutic goals for BC. Moreover, this review aims to confirm the signal pathways, therapeutic and diagnostic values of miR- 34a in BC and beyond.
Insights
MicroRNA-34a acts as a tumor suppressor in breast cancer (BC) by down-regulating gene expression and inhibiting tumor growth. Its therapeutic potential is being explored in clinical trials for BC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Breast cancer (BC) is a prevalent and deadly cancer in women.
- MicroRNA-34a (miR-34a) has been associated with breast cancer development and progression.
Purpose of the Study:
- To review the tumor-suppressing capabilities of miR-34a in breast cancer.
- To explore the therapeutic and diagnostic potential of miR-34a for BC treatment.
Main Methods:
- A comprehensive literature search was conducted on PubMed, Web of Science, and Google Scholar up to December 2018.
- Studies focusing on miR-34a and its role in breast cancer therapy were included.
- Eighty relevant articles were selected for this review.
Main Results:
- miR-34a expression is significantly down-regulated in breast tumor cells compared to normal tissues.
- Overexpression of miR-34a suppresses tumor proliferation, invasion, and metastasis by regulating key signaling pathways and genes.
- miR-34a promotes apoptosis, cell cycle arrest, and senescence, while reducing drug resistance.
Conclusions:
- miR-34a shows significant promise as a therapeutic agent for targeting breast cancer.
- Further development of miR-34a could lead to novel therapeutic strategies and diagnostic tools for BC.
- This review confirms the critical role of miR-34a in BC signaling pathways and its therapeutic value.