Wang Feng, Xia Jin, Wang Nengchao, Zong Hong
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan, P.R. China.
Onkologie. 2013;36(12):754-8. doi: 10.1159/000356978. Epub 2013 Nov 20.
Accumulating evidence has shown that microRNAs (miRNAs) are aberrantly expressed in human esophageal cancer and crucial to tumorigenesis. Herein, we identified the role of miR-145 in esophageal squamous cell carcinoma (ESCC) development in vitro and in vivo.
miR-145 expression was investigated in 40 ESCC samples as well as 5 ESCC cell lines by real-time polymerase chain reaction. Crystal violet and transwell assays were conducted to explore the effects of miR-145 on the proliferation and invasion of human ESCC cell lines, respectively. The impact of overexpression of miR-145 on putative target c-Myc was subsequently confirmed via Western blot.
miR-145 expression was frequently downregulated in ESCC specimens and cell lines compared with adjacent normal tissues (p < 0.05). Overexpression of miR-145 suppressed (p < 0.05) ESCC cell proliferation and invasion, as well as the growth of xenograft tumors in mice. Overexpression of miR-145 significantly decreased (p < 0.05) the protein level of c-Myc which has previously been identified as a direct target of miR-145.
Our results demonstrate that overexpression of miR-145 inhibits tumor growth in part by targeting c-Myc. Our findings revealed that miR-145 may act as a tumor suppressor in ESCC, and its dysregulation may be involved in the initiation and development of human ESCC.
越来越多的证据表明,微小RNA(miRNA)在人类食管癌中表达异常,对肿瘤发生至关重要。在此,我们确定了miR-145在食管鳞状细胞癌(ESCC)体外和体内发展中的作用。
通过实时聚合酶链反应研究了40例ESCC样本以及5种ESCC细胞系中miR-145的表达。分别进行结晶紫和Transwell实验,以探讨miR-145对人ESCC细胞系增殖和侵袭的影响。随后通过蛋白质印迹法证实了miR-145过表达对假定靶标c-Myc的影响。
与相邻正常组织相比,ESCC标本和细胞系中miR-145的表达经常下调(p < 0.05)。miR-145的过表达抑制了(p < 0.05)ESCC细胞的增殖和侵袭,以及小鼠异种移植肿瘤的生长。miR-145的过表达显著降低了(p < 0.05)c-Myc的蛋白质水平,c-Myc先前已被确定为miR-145的直接靶标。
我们的结果表明,miR-145的过表达部分通过靶向c-Myc抑制肿瘤生长。我们的研究结果表明,miR-145可能在ESCC中起肿瘤抑制作用,其失调可能参与人类ESCC的发生和发展。