MiR-148a and miR-152 reduce tamoxifen resistance in ER plus breast cancer via downregulating ALCAM

doi:10.1016/j.bbrc.2017.01.012

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標題:	MiR-148a and miR-152 reduce tamoxifen resistance in ER plus breast cancer via downregulating ALCAM
作者:	Chen, Ming-Jenn Cheng, Ya-Min Chen, Chien-Chung Chen, Yu-Chieh Shen, Ching-Ju
貢獻者:	Chi Mei Med Ctr, Dept Surg Chia Nan Univ Pharm & Sci, Coll Leisure & Recreat Management, Dept Sports Management Natl Cheng Kung Univ, Coll Med, Inst Clin Med, Dept Obstet & Gynecol E Da Hosp, Dept Plast & Reconstruct Surg Kaohsiung Med Univ,Kaohsiung Med Univ Hosp, Dept Gynecol & Obstet Kaohsiung Med Univ, Coll Med, Grad Inst Med
關鍵字:	MiR-148a miR-152 Breast cancer Tamoxifen ALCAM
日期:	2017-02-05
上傳時間:	2018-11-30 15:49:43 (UTC+8)
出版者:	Academic Press Inc Elsevier Science
摘要:	Activated leukocyte cell adhesion molecule (ALCAM), also called CD166 is a 105-kDa transmembrane glycoprotein of the immunoglobin superfamily. In this study, we studied the association between ALCAM expression and tamoxifen resistance in ER + breast cancer and further investigated how ALCAM is regulated in the cancer cells. IHC staining data showed that the tumor tissues from non-responders (N = 20) generally had significantly stronger ALCAM staining than that from tamoxifen responders (N = 16). In vitro cell assay also confirmed ALCAM upregulation in tamoxifen resistant (TamR) MCF-7 cells than in tamoxifen sensitive (TamS) MCF-7 cells. ALCAM overexpression significantly alleviated 4Hydroxytestosterone (4-0HT) induced cell viability inhibition and cell apoptosis in TamS MCF-7 cells, while ALCAM knockdown remarkably enhanced 4-OHT induced cell viability inhibition and cell apoptosis in TamR MCF-7 cells. Demethylation reagent treatment significantly restored miR-148a and miR-152 expression in TamR MCF-7 cells. MiR-148a and miR-152 can directly target ALCAM 3'UTR and decrease ALCAM expression. MiR-148a overexpression had similar effect as ALCAM siRNA on enhancing 4-OUT induced cell viability inhibition and cell apoptosis in TamR MCF-7 cells. MiR-152 overexpression alone caused growth inhibition and increased cell apoptosis in TamR MCF-7 cells. It also enhanced the effect of 4-OHT. Simultaneous inhibition of miR-148a and miR-152 significantly protected TamS MCF7 cells from 4-OHT induced cell viability inhibition and cell apoptosis. Based on these findings, we infer that MiR-148a and miR-152 can sensitize TamR MCF-7 cells to tamoxifen at least via downregulating ALCAM. (C) 2017 Elsevier Inc. All rights reserved.
關聯:	Biochemical and Biophysical Research Communications, v.483, n.2, pp.840-846
显示于类别:	[運動管理系] 期刊論文

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