CXCR4 3′UTR functions as a ceRNA in promoting metastasis, proliferation and survival of MCF-7 cells by regulating miR-146a activity

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• 作者：Tianjing Zheng^a ; ^b ; Jinjiang Chou^a ; ^b ; Feng Zhang^a ; ^b ; Yu Liu^a ; ^c ; Haiwei Ni^d ; Xiaoman Li^a ; ^b ; Lufeng Zheng^a ; ^b ; Tingting Tang^a ; ^b ; Liang Jin^a ; ^c ; Tao Xi^a ; ^b ; ^{xitao18@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CXCR4 ; C-X-C chemokine receptor type 4 ; SDF-1 ; stromal-derived-factor-1 ; TRAF6 ; TNF receptor-associated factor 6 ; IRAK1 ; interleukin-1 receptor-associated kinase ; EGFR ; epidermal growth factor receptor ; MTA2 ; metastasis-associated protein 2 ; NF-κB ; nuclear transcription factor-κB ; ceRNA ; competitive endogenous RNA ; miRNA ; microRNAs ; MREs ; miRNA response elements ; EMT ; epithelial-to-mesenchymal transition
• 刊名：European Journal of Cell Biology
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：94
• 期：10
• 页码：458-469
• 全文大小：5270 K

文摘

CXCR4 is the most common chemokine receptor expressed on tumor cells, and it is closely correlated with cancer cell stemness. This study was carried out to explore whether CXCR4 could function as a competitive endogenous RNA to promote metastasis, proliferation and survival in MCF-7 breast cancer cells. We validated that CXCR4, together with TRAF6 and EGFR, was directly targeted by miR-146a in MCF-7 cells. Overexpression of CXCR4 3′UTR inhibited the activity of miR-146a, thus elevating the expression of CXCR4, TRAF6 and EGFR. These oncoproteins further activated NF-κB pathway and promoted the proliferation, migration, invasion and anti-apoptotic activity of MCF-7 cells. Collectively, our study provided new insights into the function of CXCR4 in breast cancer: it promotes tumor progression as both a protein-coding gene and a non-coding RNA, complicating the mechanism by which oncogenes promote tumor progression.