miR-145 Inhibits Proliferation and Invasion of Esophageal Squamous Cell Carcinoma in Part by Targeting c-Myc
miR-145 Inhibits Proliferation and Invasion of Esophageal Squamous Cell Carcinoma in Part by Targeting c-Myc
复制标题
DOI：
10.1159/000356978
复制
发表时间：
2013-12-01
期刊：
影响因子：
0.3
通讯作者：
Zong, Hong
中科院分区：
文献类型：
--
作者：
Wang, Feng;Xia, Jin;Zong, Hong
背景：越来越多的证据表明，microRNAs （miRNAs）在人类食管癌中异常表达，在肿瘤发生中起着至关重要的作用。在这里，我们确定了miR-145在体外和体内食管鳞状细胞癌（ESCC）发展中的作用。材料和方法：采用实时聚合酶链反应检测miR-145在40个ESCC样本和5个ESCC细胞系中的表达。通过结晶紫法和transwell法分别探讨miR-145对人ESCC细胞系增殖和侵袭的影响。miR-145过表达对推测靶点c-Myc的影响随后通过Western blot得到证实。结果：与邻近正常组织相比，miR-145在ESCC标本和细胞系中的表达频繁下调（p < 0.05）。过表达miR-145可抑制小鼠ESCC细胞的增殖、侵袭及异种移植肿瘤的生长（p < 0.05）。miR-145过表达显著降低c-Myc蛋白水平（p < 0.05），而c-Myc先前被认为是miR-145的直接靶点。结论：我们的研究结果表明，miR-145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中作为肿瘤抑制因子，其失调可能参与了人类ESCC的发生和发展。
Background: 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. Material and Methods: 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. Results: 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. Conclusion: 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.