MicroRNAs that Repress BMP2 Inhibit Lung Cancer Cell Growth

Bone morphogenetic protein 2 (BMP2) protein and RNA levels are markedly elevated in human lung tumors relative to non‐malignant lung tissue. High BMP2 expression in lung tumors is associated with poor patient prognosis and laboratory experiments indicate that BMP2 promotes lung tumor tumorigenesis. The BMP2 3′untranslated region (3′UTR) bears potent suppressor elements whose function is impaired in malignant lung cells. Nearly 40 miRNAs may interact with the BMP2 3′UTR. To identify miRNAs that regulate BMP2 expression specifically in lung tumors, we used the Illumina v2 MiRNA Expression Profiling Assay to compare the abundance of miRNAs from non‐transformed BEAS‐2B cells and 3 lines of malignant lung cells (A549, BEAStra1, and BEAS tra2). Out of 1145 miRNAs, 85 miRNAs were reduced and 41 miRNAs were increased in all 3 transformed lines (p‐value less than or = 0.05). The abundances of ten miRNAs predicted to interact with the BMP2 transcript inversely correlated with BMP2 secretion. We are testing the effects of these 10 miRNAs as well as two that may compete with nucleolin, a BMP2 repressor, and HuR, a BMP2 activator, in A549 lung adenocarcinoma cells. The six miRNAs tested so far alter the expression of reporter genes bearing the BMP2 3′UTR. Several miRNAs also reducedA549 cell proliferation and survival. These miRNAs may function as tumor suppressors via repression of BMP2 synthesis.