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

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Abstract

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.

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Data availability

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.

Abbreviations

ChIP:

Chromatin immunoprecipitation

EMT:

Epithelial-mesenchymal transition

FBS:

Fetal bovine serum

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GEO:

Gene Expression Omnibus

GSEA:

Gene set enrichment analysis

HDAC6:

Histone deacetylase 6

HRP:

Horseradish peroxidase

RT-qPCR:

Reverse transcription-quantitative PCR

shRNA:

Short hairpin RNA

TBST:

Tris-buffered saline with Tween

TMEM100:

Transmembrane protein 100

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Funding

This work was supported by Natural Science Research Project of Department of Education of Liaoning Province (JYTQN2020036).

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Author notes

  1. Yanyun Wang and Minwen Ha contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Renmin Street, Guta District, Jinzhou, 121000, Liaoning, People’s Republic of China

    Yanyun Wang, Minwen Ha & Lin Zhang

  2. Department of Radiology and Medical Imaging, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, Liaoning, People’s Republic of China

    Man Li

  3. Department of Medical College, Medical College of Jinzhou Medical University, Jinzhou, 121000, Liaoning, People’s Republic of China

    Yitong Chen

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  1. Yanyun Wang
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Contributions

YYW, MWH conceived and designed the experiments; ML performed the experiments; YYW, MWH, LZ and YTC analyzed and interpreted the data; YYW wrote the manuscript; MWH and ML revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Minwen Ha.

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The authors declare no competing interests.

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The study was permitted by the Ethics Committee of the First Affiliated Hospital of Jinzhou Medical University. All animal experiments were conducted as per the Guide for the Care and Use of Laboratory Animal by International Committees.

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Wang, Y., Ha, M., Li, M. et al. Histone deacetylase 6-mediated downregulation of TMEM100 expedites the development and progression of non-small cell lung cancer. Human Cell 35, 271–285 (2022). https://doi.org/10.1007/s13577-021-00635-8

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  • DOI: https://doi.org/10.1007/s13577-021-00635-8

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