Certain microRNAs Boost Gene Expression

Researchers in Canada have found that certain microRNAs (miRNA) elevate protein expression, challenging conventional wisdom that the only role the tiny molecules play is in silencing gene expression. Because they function in dividing cells—including tumor cells—the findings have implications for miRNA-based therapeutics.

Only a few nucleotides in length, microRNAs, or miRNAs for short, don’t encode proteins. Instead, they largely downregulate protein production by silencing the expression of certain genes. One class of cellular machinery regulated by miRNAs are the enzymes involved in mediating glycosylation, which add carbohydrates to certain proteins. In cancer cells, however, this process can be highly dysregulated, suggesting that miRNAs could be doing something unusual.

Lara Mahal and colleagues and University of Alberta (UA) set out to investigate exactly how miRNAs function within the glycosylation process, and whether the molecules might be functioning in a new way.

In a previous work, the UA team developed a fluorescence assay that analyzes how miRNAs interact with their targets and whether they increase or decrease the amount of protein produced. Mahal and colleagues used the assay to investigate the regulation of cancer-related glycosylation enzymes ST6GAL1 and ST6GAL2, and found that for the former, the miRNAs appeared to directly upregulate the process in noncancerous human cells. They also tested for miRNA-mediated upregulation in multiple cancer cell lines and observed the same results.

The researchers say that this work expands the understanding of how miRNAs work, an important consideration for using miRNA-based therapeutics in both current and future clinical trials.

The findings were published recently in ACS Central Science.