Abnormal accumulation of human transmembrane (TMEM)-176A and 176B proteins is associated with cancer pathology

Abstract

Transmembrane (TMEM)-176A and 176B proteins belong to the MS4A family of proteins whose function in the immune system remains unclear. TMEM176A transcripts were previously shown to be elevated in liver cancer or kidney tissue with proteinuria, while marked changes in TMEM176B transcripts have been found in tolerated tissue allografts and neoplastic fibroblasts. To study the functional relationship between human TMEM176A and 176B and their putative link to cancer, we used polymerase chain reaction and biochemical assays. Here, we show that TMEM176A and 176B are widely expressed in all human tissues examined. Co-immunoprecipitation of heterologously expressed TMEM176A and 176B revealed direct physical interaction. To determine the relevance of such interaction to cancer pathology, we analyzed biopsied tissue samples from a variety of normal and cancer tissues. Our data reveal that human TMEM176A and 176B protein levels are significantly elevated in lymphoma, but not in normal tissues. The protein levels of TMEM176A are also significantly increased in lung carcinoma. Finally, analysis of the protein expression ratio of TMEM176A over 176B showed significant differences between normal and cancer tissues of the breast, lymph, skin, and liver, which indicates that both TMEM proteins could be potential useful markers for certain human cancers.

Genome-wide interaction study of gene-by-occupational exposure and effects on FEV1 levels

“…18,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] Several identified SNPs were located in or near genes that might be involved in biological pathway leading to lung function impairment (ie, GALNT13 and PCDH9, respectively). GALNT13 belongs to the GalNAcT family of enzymes, which initiate O-glycosylation of mucins.…”

“…31 Another study showed that TMEM16A expression levels in the lungs were low, yet proteins levels were increased in patients with lung carcinoma. 43 CHR, Chromosome; FVC, forced vital capacity.…”

Integrative Genome-Wide Analysis of the Determinants of Rna Splicing in Kidney Renal Clear Cell Carcinoma

“…1, Panel B). It is notable that the accumulation of TMEM176A/B has been linked to several other cancer types 21 previously. Moreover, we also found non-membrane associated genes with exclusive intron expression that are known to have links to cancer, such as secretagogin (SCGN) 22 involved in cell proliferation, the cytochrome P450 epoxygenase CYP2J2 23 or the hypoxia-inducible factor EGLN3.…”

“…Other top-ranked membrane-associated proteins show stronger known links to cancer, such as the transmembrane collagen COL23A1 20 or the transmembrane protein 176A. 21 Encouragingly, the latter as well as its heterologous protein TMEM176B also appeared on top of the list of genes that show exclusive intron expression and harbor significant sQTL (Fig. 1, Panel B).…”

(p)ppGpp modulates cell size and the initiation of DNA replication in Caulobacter crescentus in response to a block in lipid biosynthesis

“…Real-time qPCR was performed as previously described (Cuajungco et al, 2012), with minor modifications appropriate for our experiments. The amplification reactions were performed in a Bio-Rad CFX96 machine using SensiMix SYBR Green Master Mix (Bioline) with the following thermocycling conditions: 5 min at 95 uC followed by 40 cycles of 30 s at 95 uC, 45 s at 55 uC, 30 s at 72 uC.…”