Oncogene LSD1 is epigenetically suppressed by miR-137 overexpression in human non-small cell lung cancer.

We examined the epigenetic regulation of microRNA-137 (miR-137) on lysine-specific demethylase 1 (KDM1A, or LSD1) induced oncogenic effects in NSCLC. NSCLC cell lines, A549 and H460 cells were transfected with a mammalian LSD1 overexpression plasmid. It's effects on endogenous KDM1A gene and LSD1 protein expressions were examined by qRT-PCR and western blot assays. NSCLC proliferation and migration were also examined by MTT proliferation and wound-scratch assays, respectively. In LSD1-overexpeseed NSCLC cells, lentiviral transfection was conducted to upregulated miR-137 expression. The subsequent effects of miR-137 upregulation on LSD1-mediated cancer regulations were also examined. In addition, key components of histone deacetylases-associated signaling pathways, including EZH2, HDAC1 and HDAC2 were also examined by western blot in LSD1-and miR-137-mediated NSCLC cells. Mammalian LSD1 overexpression plasmid was efficient in upregulating KDM1A gene and LSD1 protein in A549 and H460 cells. It also exerted oncogenic effects in NSCLC by promoting cancer proliferation and migration. MiR-137 was inversely correlated with LSD1 in NSCLC, as lentivirus-mediated miR-137 upregulation suppressed KDM1A/LSD1 productions and inhibited proliferation or migration in LSD1-overexpressed A549 and H460 cells. Further western blot analysis demonstrated EZH2, HDAC1 and HDAC2 were activated by LSD1, but inhibited by miR-137 in NSCLC. Oncogenic effects of LSD1 were reversely regulated by its upstream epigenetic modulator miR-137 in NSCLC. The interaction between LSD1 and miR-137 may very well involve the regulation on histone deacetylases-associated signaling pathways.

Zhang X ，Zhang X ，Yu B ，Hu R ，Hao L ... -  《-》

MicroRNA-101 exerts tumor-suppressive functions in non-small cell lung cancer through directly targeting enhancer of zeste homolog 2.

Zhang JG ，Guo JF ，Liu DL ，Liu Q ，Wang JJ ... -  《-》

FOXP4 modulates tumor growth and independently associates with miR-138 in non-small cell lung cancer cells.

Yang T ，Li H ，Thakur A ，Chen T ，Xue J ，Li D ，Chen M ... -  《-》

LINC00511 promotes the progression of non-small cell lung cancer through downregulating LATS2 and KLF2 by binding to EZH2 and LSD1.

Zhu FY ，Zhang SR ，Wang LH ，Wu WD ，Zhao H ... -  《-》

Upregulated long non-coding RNA AGAP2-AS1 represses LATS2 and KLF2 expression through interacting with EZH2 and LSD1 in non-small-cell lung cancer cells.

Li W ，Sun M ，Zang C ，Ma P ，He J ，Zhang M ，Huang Z ，Ding Y ，Shu Y ... -  《Cell Death & Disease》