MicroRNA-31 (miR-31) repressed specific tumour suppressors and, therefore, may be a novel pharmacologic target for lung cancer therapy and chemoprevention, according to data presented at the American Association for Cancer Research's101st Annual Meeting 2010.

"We have uncovered a previously unrecognized oncogenic microRNA in mouse and human lung cancers, miR-31, which exerts its effects by repressing the expression of specific tumour suppressors," said Xi Liu, Ph.D., who was a graduate student in pharmacology and toxicology at Dartmouth Medical School at the time of the study. Liu is currently a postdoctoral fellow at the National Cancer Institute, National Institutes of Health.

MicroRNAs (miRNAs) encode small RNAs that regulate gene expression. These are useful to improve classification, diagnostic and prognostic information for cancer. Liu and colleagues conducted a study to identify miRNAs that are overexpressed in lung cancers compared with those of normal lung tissues, and to identify those that function as cancer-promoting miRNAs. 

The researchers identified functionally important miR-31 target genes that included two tumour suppressors: large tumour suppressor 2 (LATS2) and PP2A regulatory subunit B alpha isoform (PPP2R2A). Expression of miR-31 was inversely related to LATS2 and PPP2R2A in both mouse and human lung cancers, according to Liu.

In a validation study, researchers detected 10 abundantly overexpressed miRNAs in a mouse model, then used human lung cancers to determine whether the same 10 were overexpressed. Findings showed three miRNAs were significantly overexpressed — miR-31, miR-136 and miR-376a.

"It was surprising that knock-down of only miR-31 repressed growth of mouse and human lung cancer cells and inhibited lung cancer formation in mice," Liu said.

Additionally, the tumour suppressors were repressed by miR-31 overexpression and substantially increased by miR-31 knock-down, which is a good predictor of loss of oncogenicity, according to Liu.

Source: The American Association for Cancer Research