MicroRNA 345, a methylation-sensitive microRNA is involved in cell proliferation and invasion in human colorectal cancer.
发表时间：2011-12-18 13:22
Aberrantmethylation hasbeenshowntotriggerthe inactivation of tumor suppressor genes during tumorigenesis. MicroRNAs (miR- NAs) have been found deregulated in human colorectal cancer (CRC), andsome ofthemmayfunctionastumor suppressorgenes. Here, we investigated CpG island promoter hypermethylation as a potential mechanism underlying miRNA disruption and iden- tifed methylation-sensitive miRNAs that might repress CRC de- velopment. We compared differential expression of miRNAs after 5-aza-2#-deoxycitidine (5-aza-dC) treatment using microarrays. DNA methylation status of the candidate miRNA was analyzed. The candidate miRNAwas transfected into CRC cells and growth- suppressive mechanisms were explored. Luciferase reporter assay and western blot were used to identify the target genes of the candidate miRNA. The expression of mir-345 was significantly increased after 5-aza-dC treatment. DNA methylation analyses of mir-345 showed high methylation levels in tumor versus normal tissues. Expression of mir-345 was significantly down-regulated in 51.6%ofCRCtissuescomparedwithcorresponding non-cancerous tissues. Low expression of mir-345 was associated with lymph node metastasis and worse histological type. Increased mir-345 function was sufficient to suppress colon cancer cell proliferation and inva- siveness in vitro. Furthermore, we identified BCL2-associated athanogene 3 (BAG3), an anti-apoptosis protein, to be a target of mir-345. These results suggested as a methylation-sensitive miRNA in CRC, mir-345 may play an important role of antineoplastic as a growth inhibitor in the development of CRC.
第一署名医院：仁济医院
