Silencing CDR1as enhances the sensitivity of breast cancer cells to drug resistance by acting as a miR‐7 sponge to down‐regulate REGγ
Authors: Wei Yang
Xiaojuan Yang
Ming Zhou
Yueping Wang
Bin Yin
Xuedong Wang
Daoping Zhou
Juan Gu
Jianmin Guo
Journal: Journal of Cellular and Molecular Medicine (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CDR1as; REGγ; breast cancer; drug resistance; miR-7.
Affiliations: Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, China., Department of Medical Laboratory Science, The Fifth People's Hospital of Wuxi, Nanjing Medical University, Wuxi, China., Department of Pathology, The Second People's Hospital of Wuxi, Nanjing Medical University, Wuxi, China., Department of Oncology, The Second People's Hospital of Anhui Province, Hefei, China., Department of Biology, College of Arts & Science, Massachusetts University, Boston, MA., Guangdong Lewwin Pharmaceutical Research Institute Co. Ltd, Guangzhou, China., Cancer Research Institute, Central South University, Changsha, China.

Abstract:  In our study, we aimed to investigate the role of CDR1as during competitive inhibition of miR-7 in the regulation of cisplatin chemosensitivity in breast cancer via regulating REGγ. RT-qPCR was applied to detect the expression of CDR1as and miR-7 in breast cancer tissues, breast cancer cell lines and corresponding drug-resistant cell lines. The correlation between CDR1as and miR-7 and between miR-7 and REGγ was evaluated. MCF-7-R and MDA-MB-231-R cells were selected followed by transfection of a series of mimics, inhibitors or siRNA. The effect of CDR1as on the half maximal inhibitor concentration (IC50), cisplatin sensitivity and cell apoptosis was also analysed. Furthermore, a subcutaneous xenograft nude mouse model was established to further confirm the effect of CDR1as on the chemosensitivity of breast cancer to cisplatin in vivo. Immunohistochemical staining was conducted to test the Ki-67 expression in nude mice. A positive correlation was found between the drug resistance and CDR1as expression in breast cancer. CDR1as could increase the resistance of breast cancer cells to cisplatin. miR-7 expression was low, while REGγ was highly expressed in MCF-7-R and MDA-MB-231-R cells. CDR1as competitively inhibited miR-7 and up-regulated REGγ. Overexpression of miR-7 could reverse the enhanced sensitivity of silenced CDR1as to drug-resistant breast cancer cells. Additionally, in vivo experiments demonstrated that CDR1as mediated breast cancer occurrence and its sensitivity to cisplatin. Silencing CDR1as decreased Ki-67 expression. Silencing CDR1as may inhibit the expression of REGγ by removing the competitive inhibitory effect on miR-7 and thus enhancing the sensitivity of drug-resistant breast cancer cells. 

Retracted: No

PubPeer comments:
 Images in Figure 2B and 5B appear to have repeated regions, although the images are not exact duplicates. Please ignore the blue boxes as a false positive. Difficult to understand how this could occur by chance. *** ![file] *** ![file] , 
 Figure 6B appears to have two images which overlap. *** ![file] , 
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