Abstract
The resistance that Triple-Negative Breast Cancer (TNBC), the most aggressive breast cancer subtype, develops against radiotherapy is a complex phenomenon involving several regulators of cell metabolism and gene expression; understanding it is the only way to overcome it. We focused this review on the contribution of the two leading classes of regulatory non-coding RNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), against ionizing radiation-based therapies. We found that these regulatory RNAs are mainly associated with DNA damage response, cell death, and cell cycle regulation, although they regulate other processes like cell signaling and metabolism. Several regulatory RNAs regulate multiple pathways simultaneously, such as miR-139-5p, the miR-15 family, and the lncRNA HOTAIR. On the other hand, proteins such as CHK1 and WEE1 are targeted by several regulatory RNAs simultaneously. Interestingly, the study of miRNA/lncRNA/mRNA regulation axes increases, opening new avenues for understanding radioresistance. Many of the miRNAs and lncRNAs that we reviewed here can be used as molecular markers or targeted by upcoming therapeutic options, undoubtedly contributing to a better prognosis for TNBC patients.
Highlights
Breast cancer (BC) is the malignant tumor with the highest number of cases diagnosed worldwide and the most common cause of death in women [1]
Mei and colleagues found that miR-15a, 15b, and 16 influence radiosensitivity of MCF7 and MDA-MB-231 breast cancer cells, observable through the enhanced duration of H2AX foci and release of the G2 arrest induced by radiation
They demonstrated the interaction between these miRNAs and the cell cycle regulator WEE1 and CHK1 mRNAs through luciferase assays, but they did not find the dramatic reduction they expected at the protein level, hinting at a more complex mechanism [65]
Summary
Breast cancer (BC) is the malignant tumor with the highest number of cases diagnosed worldwide and the most common cause of death in women [1]. Upregulated WTAPP1 promotes invasion and migration in nonsmall cell lung cancer by interacting with HAND2-S1 and decreasing its expression [43] Most interestingly, these two classes of ncRNAs can interact with each other, adding to the complexity and importance of their regulation on mRNAs. Several lncRNAs have regions complementary to miRNA sequences that compete for their binding with the target mRNA. This review describes the different miRNAs, lncRNAs, and their associations that regulate resistance against ionizing radiation-based therapies in breast cancer We found that these ncRNAs are mainly involved in DNA damage response, but they are involved in cell death, cell cycle regulation, and other functional aspects. We summarize the currently described ncRNAs involved in the alteration of these processes
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