Liu Chang, Duan Ping, Li Bo, Huang Chuntian, Jing Ying, Yan Wenhai
Department of Preventive Medicine, Luohe Medical College, Luohe, Henan 462002, P.R. China.
Department of Basic Medicine, Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
Oncol Lett. 2015 Jan;9(1):96-102. doi: 10.3892/ol.2014.2678. Epub 2014 Nov 6.
MicroRNA (miR)-29a has been associated with carcinogenesis in humans; however, its functional significance in esophageal squamous cell carcinoma (ESCC) is yet to be determined. In the present study, the expression of miR-29a was markedly downregulated in ESCC tissue and the ESCC TE-1 cell line, compared with normal esophageal tissue and cells. Furthermore, the present study identified that the forced expression of miR-29a in TE-1 cells significantly reduced cell proliferation and migration. miR-29a overexpression did not affect the expression of Notch1, however, it did increase the gene expression levels of hairy and enhancer of split 1 (Hes1), which is the key effector of the Notch signaling pathway. Direct targeting by miR-29a resulted in the downregulation of nuclear factor 1 A (Nfia), which represses the transcriptional activity of the Hes1 promoter. Furthermore, knockdown of Nfia increased Hes1 expression and inhibited cell growth in TE-1 cells. These results indicate that a low level of miR-29a expression is involved in ESCC tumorigenesis, and exogenous expression of miR-29a may repress cancer cell growth by downregulating Nfia and activating the Notch signaling pathway.
微小RNA（miR）-29a已被证实与人类癌症发生相关；然而，其在食管鳞状细胞癌（ESCC）中的功能意义尚待确定。在本研究中，与正常食管组织和细胞相比，ESCC组织和ESCC TE-1细胞系中miR-29a的表达明显下调。此外，本研究发现，在TE-1细胞中强制表达miR-29a可显著降低细胞增殖和迁移。miR-29a过表达不影响Notch1的表达，然而，它确实增加了Notch信号通路的关键效应因子毛状分裂增强子1（Hes1）的基因表达水平。miR-29a的直接靶向作用导致核因子1A（Nfia）的下调，而Nfia可抑制Hes1启动子的转录活性。此外，敲低Nfia可增加Hes1的表达并抑制TE-1细胞的生长。这些结果表明，低水平的miR-29a表达参与了ESCC的肿瘤发生，并且miR-29a的外源性表达可能通过下调Nfia和激活Notch信号通路来抑制癌细胞生长。
