, a bio/informatics shared resource is still "open for business" - Visit the CDS website

Bone morphogenetic protein-focused strategies to induce cytotoxicity in lung cancer cells.

Fotinos A, Nagarajan N, Martins AS, Fritz DT, Garsetti D, Lee AT, Hong CC, Rogers MB
Anticancer Res. 2014 34 (5): 2095-104

PMID: 24778011 · PMCID: PMC4791537

BACKGROUND - High bone morphogenetic protein (BMP)-2 expression in lung carcinoma correlates with poor patient prognosis. The present study explored strategies to repress BMP signaling.

MATERIALS AND METHODS - The cytotoxicity of BMP2-knockdown, dorsomorphin derivatives, and microRNAs was tested in transformed and non-transformed lung cells. Microarray analyses of 1,145 microRNAs in A549 lung adenocarcinoma cells and two other transformed lung cell types relative to BEAS-2B bronchial epithelial cells were performed.

RESULTS - Reduced BMP2 synthesis inhibited A549 cell growth. The dorsomorphin derivative LDN-193189, but not DMH1 or DMH4, was strongly cytotoxic towards A549 cells, but not towards BEAS-2B cells. Microarray analysis revealed that 106 miRNAs were down-regulated and 69 miRNAs were up-regulated in the three transformed lines. Three down-regulated miRNAs, hsa-mir-34b, hsa-mir-34c-3p, and hsa-miR-486-3p, repressed a BMP2 reporter gene and were cytotoxic in A549 cells, but not towards BEAS-2B cells.

CONCLUSION - The observed cytotoxicity suggests that reducing BMP signaling is a useful line of attack for therapy of lung cancer.

MeSH Terms (17)

Adenocarcinoma Adenocarcinoma of Lung Antineoplastic Agents Bone Morphogenetic Protein 2 Cell Line, Tumor Cell Proliferation Enzyme-Linked Immunosorbent Assay Gene Knockdown Techniques Humans Lung Neoplasms MicroRNAs Oligonucleotide Array Sequence Analysis Pyrazoles Pyrimidines Reverse Transcriptase Polymerase Chain Reaction RNA Interference Signal Transduction

Connections (2)

This publication is referenced by other Labnodes entities: