MicroRNA 15a and 16 Regulate Proteostasis in Non-Small Cell Lung Cancer.

Aberrant anabolic activity is critical to tumor biology; however, much remains to be learned about the regulators of protein anabolism in cancer and how this regulation may affect cancer pathophysiology. MicroRNA (miRNA), a family of small nucleotide regulatory molecules, may serve as a potential source of proteostatic regulation. Here, we examined the ability of two co-transcribed miRNA species, miR15a and miR16 (jointly described as miR15a/16) to regulate protein handling and pathophysiology in non-small cell lung cancer (NSCLC). We found that miR15a/16 regulates genes in numerous metabolic and pathological pathways, including those related to protein metabolism. Transfection of cellular models of NSCLC with miR15a/16 mimetics caused reductions in both cell growth and protein synthesis rates. These findings indicate that miR15a/16 acts as regulators of protein anabolism in NSCLC, serving as novel metabolic regulators and potential clinical therapeutic targets for malignant lung cancer.