BMP4 Upregulation Is Associated with Acquired Drug Resistance and Fatty Acid Metabolism in EGFR-Mutant Non-Small-Cell Lung Cancer Cells

Molecular Therapy. Nucleic Acids
Duc-Hiep BachSang Kook Lee

Abstract

Lung cancer is the leading cause of cancer-associated deaths worldwide. In particular, non-small-cell lung cancer (NSCLC) cells harboring epidermal growth factor receptor (EGFR) mutations are associated with resistance development of EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. Recent findings suggest that bone morphogenetic proteins (BMPs) and microRNAs (miRNAs) might act as oncogenes or tumor suppressors in the tumor microenvironment. In this study, for the first time, we identified the potential roles of BMPs and miRNAs involved in EGFR-TKI resistance by analyzing datasets from a pair of parental cells and NSCLC cells with acquired EGFR-TKI resistance. BMP4 was observed to be significantly overexpressed in the EGFR-TKI-resistant cells, and its mechanism of action was strongly associated with the induction of cancer cell energy metabolism through the modulation of Acyl-CoA synthetase long-chain family member 4. In addition, miR-139-5p was observed to be significantly downregulated in the resistant NSCLC cells. The combination of miR-139-5p and yuanhuadine, a naturally derived antitumor agent, synergistically suppressed BMP4 expression in the resistant cells. We further confirmed that LDN-193189, a small molecule BMP r...Continue Reading

Citations

Sep 10, 2020·Signal Transduction and Targeted Therapy·Huibin SongChang Zou
Sep 17, 2020·Cancer Chemotherapy and Pharmacology·Ludovic FournelMarco Alifano
Oct 27, 2018·International Journal of Molecular Sciences·Duc-Hiep BachSang Kook Lee
Jul 28, 2019·Cancer Research·Duc-Hiep BachAnil K Sood
Jan 17, 2021·Journal of Cellular and Molecular Medicine·Xiaotong ZhangChuize Kong
Jul 13, 2021·Frontiers in Cell and Developmental Biology·Zhu-Hui YuanJun-Jie Wang
Oct 6, 2021·Journal of Cell Communication and Signaling·Renu SharmaBithiah Grace Jaganathan

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Methods Mentioned

BETA
xenografts
PCR
RIP
xenograft
transfection
immunoprecipitation
pull down
Knockdown
Profiler
protein array

Software Mentioned

NMRView J
Affymetrix
R
Affymetrix Expression Console
TableCurve
Affymetrix GeneChip Command Console

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