Abstract
Abstract Tamoxifen is a conventional treatment option for breast cancer patients diagnosed with estrogen receptor (ER)-positive tumors. However, a significant number of these patients eventually develop resistance to tamoxifen during therapy, and thus the management of such tamoxifen-resistant patients remains a clinical challenge. In an effort to identify novel targets for the treatment of tamoxifen-resistant tumors, we observed increased expression of microRNA 10b (miR-10b) in ER-positive MCF-7 cells-derived tamoxifen-resistant cells (MCF7TR). The miR-10b has been implicated in invasion and metastasis but its role, if any, in drug resistance of breast cancer cells has never been investigated. To ascertain the mechanistic role of miR-10b in tamoxifen resistance, we downregulated its levels in MCF7TR cells and in addition we also overexpressed miR-10b by transfecting MCF-7 cells with pre-miR-10b. We found that the downregulation of miR-10b in MCF7TR cells led to increased sensitivity to tamoxifen whereas overexpression of miR-10b in MCF-7 cells led to increased resistance to tamoxifen. During our mechanistic investigation, we found that increased expression of miR-10b downregulated the expression of HDAC4 in MCF7TR cells. Inactivation of HDAC4 using HDAC4-specific siRNA transfection in MCF-7 cells led to the acquisition of tamoxifen resistance. Moreover, further reduction of HDAC4 in MCF7TR cells by HDAC4-specific siRNA transfection resulted in further enhancement of tamoxifen resistance. In summary, we have identified miR-10b-HDAC4 nexus as one of the molecular mechanism of tamoxifen resistance, and thus targeting this nexus could become a novel targeted therapeutic approach for the treatment of tamoxifen-resistant breast cancer.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
