MiR-429 up-regulation induces apoptosis and suppresses invasion by targeting Bcl-2 and SP-1 in esophageal carcinoma
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MicroRNAs (miRNAs) may act as oncogenes or tumor suppressor genes and, as such, they may play a role in cancer development. We investigated miR-429 expression levels in a cohort of esophageal carcinomas (EC) to assess its impact on EC cell growth, apoptosis and invasion.
qRT-PCR assays were used to quantify miR-429 expression levels in 32 paired EC samples and adjacent non-neoplastic tissues. Assays for cell growth, apoptosis, caspase activity and trans-well invasion were used to evaluate the effects of miR-429 expression on EC cells. Luciferase reporter and Western blotting assays were used to test whether the Bcl-2 and specificity protein 1 (SP1) mRNAs serve as major targets of miR-429.
The expression levels of miR-429 in EC tissues were found to be lower than those in adjacent non-neoplastic tissues (P < 0.05). This relatively low expression was found to be significantly associated with the occurrence of lymph node metastases (P < 0.05). Apoptosis and migration rates were found to be significantly higher in two EC-derived cell lines (EC9706 and KYSE30) transfected with a miR-429 agomir (P < 0.05). Subsequent Western blotting and luciferase reporter assays showed that miR-429 can bind to putative binding sites within the Bcl-2 and SP1 mRNA 3′ untranslated regions (UTRs) to reduce their expression.
In primary EC tissues miR-429 is expressed at low levels. Up-regulation of miR-429 inhibits invasion and promotes apoptosis in EC cells by targeting Bcl-2 and SP1. Our findings suggest that Bcl-2 and SP1 may serve as major targets of miR-429. This study paves the way for a better understanding of the mechanism underlying EC pathogenesis and the development of novel, targeted therapies.
KeywordsEsophageal cancer miR-429 Apoptosis Invasion Bcl-2 SP1
This study was supported by National Natural Science Foundation of China (No. 81272188).
Conflict of interest
The authors have declared that no competing interest exists.
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