From Micro to Long: Non-Coding RNAs in Tamoxifen Resistance of Breast Cancer Cells

Abstract

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality among women. Two thirds of patients are classified as hormone receptor positive, based on expression of estrogen receptor alpha (ERα), the main driver of breast cancer cell proliferation, and/or progesterone receptor, which is regulated by ERα. Despite presenting the best prognosis, these tumors can recur when patients acquire resistance to treatment by aromatase inhibitors or antiestrogen such as tamoxifen (Tam). The mechanisms that are involved in Tam resistance are complex and involve multiple signaling pathways. Recently, roles for microRNAs and lncRNAs in controlling ER expression and/or tamoxifen action have been described, but the underlying mechanisms are still little explored. In this review, we will discuss the current state of knowledge on the roles of microRNAs and lncRNAs in the main mechanisms of tamoxifen resistance in hormone receptor positive breast cancer. In the future, this knowledge can be used to identify patients at a greater risk of relapse due to the expression patterns of ncRNAs that impact response to Tam, in order to guide their treatment more efficiently and possibly to design therapeutic strategies to bypass mechanisms of resistance.

MicroRNAs miR-142-5p, miR-150-5p, miR-320a-3p, and miR-4433b-5p in Serum and Tissue: Potential Biomarkers in Sporadic Breast Cancer

“…The potential diagnostics of circulating miRNAs, especially from exosomes (EV-miRNAs), has already been discussed ( Liu et al, 2019 ; Ozawa et al, 2020b , 2020a ). In addition, other non-coding RNAs (nc-RNAs) are emerging as potential biomarkers as long non-coding RNAs ( Gradia et al, 2017 ; Barazetti et al, 2021 ; Mathias et al, 2021 ) and circular RNAs (circ-RNAs) ( Qian et al, 2018 ; Ameli-Mojarad et al, 2021 ; de Palma et al, 2022 ). Ameli-Mojarad et al (2021) showed a higher expression of circRNAs in BC tissues than in adjacent tissues.…”

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

“…Recently many miRNAs have been found to be associated with the progression of tamoxifen resistance of breast cancer cells [89][90][91], however, the miRNAs involvement in…”

“…Recently many miRNAs have been found to be associated with the progression of tamoxifen resistance of breast cancer cells [89][90][91], however, the miRNAs involvement in the resistance development is still unclear. Here we have found that some miRNAssuppressors of oestrogen signalling are overexpressed in the exosomes of the tamoxifenresistant cells.…”

Relationship of micro-RNA, mRNA and eIF Expression in Tamoxifen-Adapted MCF-7 Breast Cancer Cells: Impact of miR-1972 on Gene Expression, Proliferation and Migration

“…Besides the changes in mRNA expression, alterations in micro RNA content have also been observed. A recent review listed about 75 micro RNAs associated with tamoxifen resistance [ 17 ]. For example, mir-375 [ 18 ], mir-519a [ 19 ] miR-181b [ 20 ], miR-363, [ 21 ] or miR-451 [ 22 ] were functionally associated with tamoxifen resistance.…”