Newly Discovered MicroRNAs are ‘Crucial Drivers’ of Lung Cancer

Newly discovered microRNAs harbored by tumor-initiating cancer stem cells, drive tumorigenesis and metastasis of non-small cell lung cancer (NSCLC)-and a new investigational therapeutic, locked nucleic acid, shows preclinical promise against them, researchers report in Nature Communications.

Normal microRNAs (miRNAs) are involved in post-transcriptional gene silencing. But they are often abnormal in cancer cells, potentially contributing to tumors’ heterogeneity and evolutionary potential for drug resistance.

Two newly described miRNAs that are harbored in some cancer stem cells, miR-1246 and miR-1290, are “crucial drivers” of tumorigenesis and progression, the researchers reported.

Inhibiting either of these two miRNAs diminished tumor formation and metastasis, the researchers found, working at the Genome Institute of Singapore.

“Functionally, direct inhibition of either miRNA with locked nucleic acid administered systemically, can arrest the growth of established patient-derived xenograft tumors [in mice], thus indicating that these miRNAs are clinically useful as biomarkers for tracking disease progression and as therapeutic targets,” they reported.

Changes over time in the circulating (serum) levels of these molecules in patients with NSCLC are also associated with clinical responses to treatment, suggesting that they could be used in liquid biopsies for predicting metastasis or recurrence of lung cancer, they wrote.

“Targeting the most recalcitrant cells in a tumor allows us to attack the root cause of cancer,” concluded Genome Institute of Singapore Director Ng Huck Hui, PhD, in a press release.