GATA binding protein 5-mediated transcriptional activation of transmembrane protein 100 suppresses cell proliferation, migration and epithelial-to-mesenchymal transition in prostate cancer DU145 cells

Abstract

It has been reported that transmembrane protein 100 (TMEM100) acts as a tumor regulator in several types of cancers. However, whether the expression of TMEM100 is associated with the development and prognosis of prostate cancer (PCa) remains elusive. Therefore, the present study aimed to uncover the role of GATA binding protein 5 (GATA5)-mediated activation of TMEM100 in the proliferation, migration and epithelial-to-mesenchymal transition (EMT) of PCa cells. The expressions of TMEM100 and GATA5 in PCa patients were analyzed by the GEPIA database. The binding site of GATA5 and TMEM100 promoter was predicted by the JASPAR database. Expressions of TMEM100 and GATA5 in PCa cells were detected by qRT-PCR and Western blot analysis. Cell Counting Kit 8 and colony formation assays were performed to measure cell proliferation. In addition, cell migration, invasion and the expression of EMT-associated proteins were evaluated using wound healing, transwell assay and Western blotting assays, respectively. The bioinformatics analysis revealed that TMEM100 was downregulated in PCa and was associated with overall survival of PCa. In addition, TMEM10 overexpression attenuated cell proliferation, migration, invasion and EMT in PCa cells. The interaction between TMEM100 and GATA5 was verified using dual luciferase reporter and chromatin immunoprecipitation assays. Furthermore, the results showed that GATA5 was downregulated and GATA5 silencing reversed the inhibitory effects of TMEM10 on PCa cells. Overall, the current study suggested that the GATA5-mediated transcriptional activation of TMEM100 could affect the behavior of PCa cells and was associated with poor prognosis in PCa.

The Role of a Lung Vascular Endothelium Enriched Gene TMEM100

“…Furthermore, TMEM100 was markedly downregulated in pancreatic cancer (PCa) tissues. Overexpression of TMEM100 attenuates the proliferation, migration, invasion and EMT in DU145 cells, a PCa cell line 34 . Similarly, TMEM100 was shown to decrease in the prostate cancer patients, and low TMEM100 expression was associated with advanced tumor stage and metastasis.…”

“…However, we did not observe significantly change of TMEM100 expression in the lung of hypoxia treated mice. TMEM100 expression is downregulated in multiple cancer tissue and cell lines including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), colorectal cancer, gastric cancer, and PCa 28,31,34,50,51 . Liu et al demonstrated that GATA binding 5 (GATA5) , a transcription factor of GATA protein family 52 , binds to TMEM100 promoter and transcriptionally activates TMEM100 and suppresses PCa progression 34 .…”

“…TMEM100 expression is downregulated in multiple cancer tissue and cell lines including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), colorectal cancer, gastric cancer, and PCa 28,31,34,50,51 . Liu et al demonstrated that GATA binding 5 (GATA5) , a transcription factor of GATA protein family 52 , binds to TMEM100 promoter and transcriptionally activates TMEM100 and suppresses PCa progression 34 . Furthermore, Wang et al found that there was an obvious H3K27ac modification in the promoter sequence in TMEM100 and a significantly negative correlation between TMEM100 and histone deacetylase 6 (HDAC6) expression in TCGA-LUAD (lung adenocarcinoma) and LUSC (lung squamous cell carcinoma) patients 33 .…”

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

“…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).…”

“…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 ). Elevated TMEM100 level inhibits pulmonary metastasis of GC cells and enhances xenograft tumor sensitivity to 5-FU therapy ( 9 ).…”