Histone deacetylase 6-mediated downregulation of TMEM100 expedites the development and progression of non-small cell lung cancer.

The significance of epigenetic modulation, involving acetylation, methylation, as well as ubiquitination has been indicated in the regulation of gene expression and tumor progression. Here, we elucidated the role of histone deacetylase 6 (HDAC6) in regulating epithelial-mesenchymal transition (EMT)-mediated metastasis via mRNA in non-small cell lung cancer (NSCLC). Three microarrays associated with lung cancer metastasis or recurrence, GSE23361, GSE7880 and GSE162102, were downloaded from the GEO database. Transmembrane protein 100 (TMEM100) was revealed to be the only one mRNA that was significantly downregulated in three microarrays. TMEM100, poorly expressed in lung cancer tissues, was associated with poor prognosis of lung cancer patients. Moreover, TMEM100 transcription was regulated by HDAC6 which repressed TMEM100 expression by deacetylation modification on the TMEM100 promoter. Knockdown of HDAC6 or overexpression of TMEM100 in NSCLC cells significantly inhibited TGF-β1-induced EMT and metastasis and suppressed the activation of Wnt/β-catenin signaling pathway. Altogether, our study highlights HDAC6 as a lung cancer metastasis supporter through the suppression of TMEM100 and the induction of Wnt/β-catenin signaling pathway.