PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Huiling He; Krystian Jazdzewski; Wei Li; Sandya Liyanarachchi; Rebecca Nagy; Stefano Volinia; George A Calin; Chang-Gong Liu; Kaarle Franssila; Saul Suster; Richard T Kloos; Carlo M Croce; Albert de la Chapelle Journal: Proc Natl Acad Sci U S A Date: 2005-12-19 Impact factor: 11.205
Authors: S Uhlmann; J D Zhang; A Schwäger; H Mannsperger; Y Riazalhosseini; S Burmester; A Ward; U Korf; S Wiemann; O Sahin Journal: Oncogene Date: 2010-05-31 Impact factor: 9.867
Authors: Nozomu Yanaihara; Natasha Caplen; Elise Bowman; Masahiro Seike; Kensuke Kumamoto; Ming Yi; Robert M Stephens; Aikou Okamoto; Jun Yokota; Tadao Tanaka; George Adrian Calin; Chang-Gong Liu; Carlo M Croce; Curtis C Harris Journal: Cancer Cell Date: 2006-03 Impact factor: 31.743
Authors: Aaron J Schetter; Suet Yi Leung; Jane J Sohn; Krista A Zanetti; Elise D Bowman; Nozomu Yanaihara; Siu Tsan Yuen; Tsun Leung Chan; Dora L W Kwong; Gordon K H Au; Chang-Gong Liu; George A Calin; Carlo M Croce; Curtis C Harris Journal: JAMA Date: 2008-01-30 Impact factor: 56.272