Zhang Jianxiang, Ma Yanmei, Wang Shoujun, Chen Fu, Gu Yuanting
Department of General Surgery, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, China.
Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, China.
Int J Clin Exp Pathol. 2015 Nov 1;8(11):14472-8. eCollection 2015.
C/EBPα plays an important role in the modulation of cell proliferation, differentiation or apoptosis in various tissues. Most recently, reduced expression of C/EBPα and growth inhibitory effect was found in primary mammary carcinomas. However, the underlying mechanism is still not fully aware. Here, we firstly identified miR-134 as a target of C/EBPα in MCF7 breast cancer cell lines. C/EBPα overexpression promoted miR-134 expression, causing suppression of apoptosis- protective genes CREB and Bcl-2, and resulted in the proliferation inhibition of MCF7 cells. Moreover, anti-miR-134 rescued the proliferation inhibition of MCF7 cells and the suppression of anti-apoptotic genes CREB and Bcl-2 caused by C/EBPα overexpression. Collectively, C/EBPα inhibited cell growth in breast cancer cells via a novel pathway miR-134/CREB.
C/EBPα在多种组织的细胞增殖、分化或凋亡调节中发挥重要作用。最近,在原发性乳腺癌中发现C/EBPα表达降低及生长抑制作用。然而,其潜在机制仍未完全明确。在此,我们首先在MCF7乳腺癌细胞系中鉴定出miR-134是C/EBPα的一个靶点。C/EBPα过表达促进miR-134表达,导致凋亡保护基因CREB和Bcl-2受到抑制,并致使MCF7细胞增殖受到抑制。此外,抗miR-134挽救了MCF7细胞的增殖抑制以及由C/EBPα过表达引起的抗凋亡基因CREB和Bcl-2的抑制。总体而言,C/EBPα通过一条新的miR-134/CREB途径抑制乳腺癌细胞的生长。