High expression of TMEM40 contributes to progressive features of tongue squamous cell carcinoma

Abstract

Transmembrane protein 40 (TMEM40) is a 23-kDa protein and its association with tongue squamous cell carcinoma (TSCC) remains unclear. This study aimed to investigate the expression and clinical significance of TMEM40 in TSCC and its roles in TSCC cells. Immunohistochemical analysis was performed to detect the expression levels of TMEM40 in 60 tongue tissue samples. Furthermore, TMEM40 was overexpressed and inhibited in two TSCC cell lines by transfection with pEZ-M98-TMEM40 plasmid or TMEM40 small interfering RNA, respectively. Cell Counting Kit-8 and colony formation assays were used to investigate the effects of TMEM40 on cell proliferation and colony formation ability, respectively. Flow cytometry was performed to determine cell apoptosis and cycle conditions of transfected cells. Wound-healing and Transwell assays were processed to explore the effects of TMEM40 on cell migration and invasion, respectively. The results indicated that TMEM40 expression levels were significantly increased in TSCC tissues compared with adjacent normal tongue tissues (P<0.01). Clinicopathological analysis revealed that TMEM40 expression was positively correlated with pathological TNM (pTNM) status (P<0.05), histological grade (P<0.001) and clinical stage (P<0.01), but not with sex or age. Results of cell proliferation, apoptosis, migration and invasion assays indicated that when TMEM40 had been successfully overexpressed or knocked down in CAL27 and SCC9 TSCC cell lines, cell growth and invasion increased in the TMEM40 overexpressing cells, while they decreased in TMEM40-knockdown cells. Furthermore, experiments revealed that TMEM40 knockdown resulted in increased levels of p53 and Bax, and decreased levels of MMP-9, which indicated that TMEM40 regulated cell apoptosis and migration via involvement of p53, Bax and MMP-9 in TSCC cells. Our findings indicated that increased expression of TMEM40 contributed to progressive features of TSCC via regulation of p53, Bax and MMP-9.

Dissecting the DNA binding landscape and gene regulatory network of p63 and p53

“…Out of the 180 high-probability p63 target genes 32 (28 up- and four down-regulated) are also identified as being commonly up- or down-regulated in SCCs compared to non-SCC cancers ( Cancer Genome Atlas Research Network et al, 2018 ; Table 1 ). Importantly, several of the genes commonly up-regulated by p63 as well as in SCC have been identified to promote SCC growth or invasion, such as LAD1 ( Abe et al, 2019 ), TMEM40 ( Zhang et al, 2019 ), FGFBP1 ( Czubayko et al, 1997 ), IL1B ( Lee et al, 2015 ), FAT2 ( Dang et al, 2016 ), FOSL1 ( Usui et al, 2012 ), LPAR3 ( Brusevold et al, 2014 ), MMP14 ( Pang et al, 2016 ), and RASSF6 ( Zheng et al, 2019a ). Therefore, we asked whether the set of 28 up-regulated direct p63 targets correlates with patient survival.…”

“…296such as LAD1(Abe et al, 2019), TMEM40(Zhang et al, 2019), FGFBP1(Czubayko et al, 297 1997), IL1B(Lee et al, 2015), FAT2(Dang et al, 2016), FOSL1(Usui et al, 2012), LPAR3…”

Transcriptomic analysis reveals differential gene expression, alternative splicing, and novel exons during mouse trophoblast stem cell differentiation

“…A shift in expression from a full-length Tnnt1 protein (in TSCs) to a shorter isoform in TGCs may have a similar role in migration and actin dynamics in TGCs [ 80 , 81 ]. Other genes with differentially expressed exons are known to be involved in several biological processes including cell growth, invasion, migration, apoptosis, and differentiation [ 82 , 83 ]. Cell type-specific expression of the identified exons may be important in maintaining stemness or inducing differentiation of trophoblast stem cells.…”

Identification of hub genes in peripheral blood mononuclear cells for the diagnosis of hepatocellular carcinoma using a weighted gene co‑expression network analysis

“…TMEM40 encodes a 23 kDamulti-pass membrane protein. A previous study revealed that TMEM40 is localized at chromosome 3p25.2 and is believed to play a key role in collagen-induced arthritis ( 20 ). The expression levels of TMEM40 were significantly higher in bladder cancer tissues and were associated with clinical grade ( 21 ).…”