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

Wang, Yanyun; Ha, Minwen; Li, Man; Chen, Yitong

doi:10.1007/s13577-021-00635-8

Cited by 16 publications

(21 citation statements)

References 32 publications

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“…the researchers found that overexpressing TMEM100 in NSCLC inhibited cell proliferation and metastasis; conversely, knocking down TMEM100 promoted cell proliferation ability in NSCLC 32 . Finally, in a study by Wang et al, the researchers showed that TMEM100 was a factor in inhibiting epithelialmesenchymal transition (EMT) in NSCLC 33 . By overexpressing TMEM100 in NSCLC cells, the researchers found that EMT expression markers were impaired, the morphology of NSCLC cells changed from mesenchymal back to epithelial, and impairment in the proliferative ability of NSCLC cells 33 .…”

Section: Role Of Tmem100mentioning

confidence: 99%

The Role of a Lung Vascular Endothelium Enriched Gene TMEM100

Pan¹,

Liu²,

Dai³

2023

Preprint

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Transmembrane protein 100 (TMEM100) plays an important role in angiogenesis, vascular morphogenesis, integrity and cardiovascular development. TMEM100 is a downstream target of the BMP9/10 and BMPR2/ALK1 signaling pathways. Our recent study demonstrates TMEM100 is a lung endothelium enriched gene. Endothelial-specific deletion of Tmem100 impairs lung endothelial cells regeneration. Activation of Tmem100 signaling represents a novel strategy for lung vascular repair and regeneration. It is interesting and important to understand the roles of TMEM100 in the physiological and pathological conditions. In this review, we summarized the current knowledge of TMEM100.

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Section: Role Of Tmem100mentioning

confidence: 99%

The Role of a Lung Vascular Endothelium Enriched Gene TMEM100

Pan¹,

Liu²,

Dai³

2023

Preprint

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“…TGF-β was shown to induce autophagy in cancer-associated fibroblasts and promote EMT and metastasis [ 118 ]. Both the downregulation of HDAC6 and the overexpression of transmembrane protein 100 (TMEM100) were shown to inhibit TGF-β1-induced EMT and suppress the activation of the Wnt/β-catenin signaling pathway in NSCLCs [ 119 ]. A low level of TMEM100 predicted the poor prognosis of patients with lung cancers [ 119 ].…”

Section: Role Of Hdac6 In Autophagymentioning

confidence: 99%

“…Both the downregulation of HDAC6 and the overexpression of transmembrane protein 100 (TMEM100) were shown to inhibit TGF-β1-induced EMT and suppress the activation of the Wnt/β-catenin signaling pathway in NSCLCs [ 119 ]. A low level of TMEM100 predicted the poor prognosis of patients with lung cancers [ 119 ]. Snail2 interacted with HDAC6 and recruited HDAC6 to the promoter sequences of E-cadherin, which decreased E-cadherin expression in colorectal cancer cells [ 120 ].…”

Section: Role Of Hdac6 In Autophagymentioning

confidence: 99%

Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance

Shim

Jeoung

2022

IJMS

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Histone deacetylases (HDACs) regulate gene expression through the epigenetic modification of chromatin structure. HDAC6, unlike many other HDACs, is present in the cytoplasm. Its deacetylates non-histone proteins and plays diverse roles in cancer cell initiation, proliferation, autophagy, and anti-cancer drug resistance. The development of HDAC6-specific inhibitors has been relatively successful. Mechanisms of HDAC6-promoted anti-cancer drug resistance, cancer cell proliferation, and autophagy are discussed. The relationship between autophagy and anti-cancer drug resistance is discussed. The effects of combination therapy, which includes HDAC6 inhibitors, on the sensitivity of cancer cells to chemotherapeutics and immune checkpoint blockade are presented. A summary of clinical trials involving HDAC6-specific inhibitors is also presented. This review presents HDAC6 as a valuable target for developing anti-cancer drugs.

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“…This suggests that TMEM100 is most likely to be involved in processes such as malignant tumor metastasis and the induction of microangiogenesis. TMEM100 exhibited a clear inhibition of metastasis and proliferation in lung cancer, prostate cancer (PC), hepatocellular carcinoma (HCC) and gastric cancer (GC), and is correlated with the prognostic outcomes of above malignancies (5)(6)(7)(8)(9)(10)(11). In lung adenocarcinoma, miR-421 could be sponged by circ_0000567 and directly target TMEM100 mRNA, then regulated the migration and invasion (5).…”

Section: Introductionmentioning

confidence: 99%

“…In lung adenocarcinoma, miR-421 could be sponged by circ_0000567 and directly target TMEM100 mRNA, then regulated the migration and invasion ( 5 ). And Histone deacetylase 6 (HDAC6) acted as a metastasis supporter induced the Wnt/β-catenin signaling pathway by suppressing TMEM100 expression in non-small cell lung cancer (NSCLC) ( 6 ). In PC, GATA binding protein 5-mediated transcriptional activation of TMEM100 suppresses cell proliferation, migration and epithelial-to-mesenchymal transition ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Transmembrane Protein 100 Inhibits the Progression of Colorectal Cancer by Promoting the Ubiquitin/Proteasome Degradation of HIF-1α

et al. 2022

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Transmembrane protein 100 (TMEM100) is involved in embryonic cardiovascular system development. However, the biological role of TMEM100 in human cancers, particularly colorectal cancer (CRC), is unclear. In this study, tissue microarrays were stained using immunohistochemistry methods to evaluate the association between TMEM100 levels and clinic-pathological features for CRC. Kaplan–Meier and log-rank tests revealed that decreased levels of TMEM100 correlated with shorter overall survival. Cox regression revealed that reduced levels of TMEM100 was an independent prognostic factor for detrimental survival in CRC. A lentiviral vector was used to overexpress TMEM100 in HCT116 cells, and small interfering RNA was used to knockdown TMEM100 in SW480 cells. The CCK-8 assay, colony formation analysis, cell cycle analysis, cell migration assay, mouse xenograft model and mouse lung metastasis model showed that TMEM100 suppressed CRC cell proliferation and migration in vitro and in vivo. IHC scores of TMEM100 and HIF-1α were significantly negatively correlated. A half-time determination analysis in which cells were treated with cycloheximide revealed that TMEM100 shortened the HIF-1α half-life. Further immunoprecipitation experimental results showed that TMEM100 promoted the ubiquitination of HIF-1α, which caused HIF-1α degradation via the 26S proteasome pathway. Angiogenesis assay and migration assay results revealed that TMEM100 suppressed the migration and angiogenesis induction capacities of HCT116 cells, but this inhibitory effect was abolished when HIF-1α degradation was blocked by MG132 treatment. These results indicated that TMEM100 inhibited the migration and the angiogenesis induction capacities of CRC cells by enhancing HIF-1α degradation via ubiquitination/proteasome pathway.

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

Cited by 16 publications

References 32 publications

The Role of a Lung Vascular Endothelium Enriched Gene TMEM100

The Role of a Lung Vascular Endothelium Enriched Gene TMEM100

Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance

Transmembrane Protein 100 Inhibits the Progression of Colorectal Cancer by Promoting the Ubiquitin/Proteasome Degradation of HIF-1α

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