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微小RNA-145通过靶向c-Myc部分抑制食管鳞状细胞癌的增殖和侵袭。

miR-145 inhibits proliferation and invasion of esophageal squamous cell carcinoma in part by targeting c-Myc.

作者信息

Wang Feng, Xia Jin, Wang Nengchao, Zong Hong

机构信息

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan, P.R. China.

出版信息

Onkologie. 2013;36(12):754-8. doi: 10.1159/000356978. Epub 2013 Nov 20.

Abstract

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.

摘要

背景

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。

材料与方法

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。

结果

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。

结论

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。

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