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Introduction
In our previous studies, a functionally unknown gene FAM172A, the family with sequence similarity 172, member A, was identified. Bioinformatics analysis demonstrated that FAM172A (C5orf21, NM_032042.5) contains an open reading frame composed of 1251 nucleotides encoding a protein comprised of 416 amino acids and an Arb2 conserved domain located in gene sequence. Online software CELLO 2.5 (http://cello.life.nctu.edu.tw/) to forcast the subcellular location of the human protein (1), was indicative of localization in the nucleus and/or cytoplasm of human FAM172A protein.
FAM172A was first identified in human aortic endothelial cells, THP-1-derived macrophages, and human aortic smooth muscle cells at the translation level through western blotting (2,3). Feng et al found that FAM172A was notably downregulated among hepatocellular carcinoma or cirrhotic patients. It indicated that FAM172A might be a novel anticancer gene, which enphasizes a crucial role in the control of cell cycle and proliferation of tumor cells (4,5).
STAT1, signaling transducer and transcription activator 1, belongs to the STAT protein family. This protein, activated by ligands including interferon-α, PDGF, and IL6, mediates the expression of various genes, which is considered to be crucial for cell activity in response to pathogens and cell stimuli (6). STAT-proteins are activated by tyrosine phosphorylation, usually by JAK kinases. They dimerize, translocate to the nucleus and activate their specific target genes (7–9). STAT1 is required for apoptosis induced by ischemia in cardiac myocytes and by tumor necrosis factor, oxysterols, and DNA damage (10,11). As an important transcription factor, STAT1 may exert an essential role in the expression of FAM172A.
We have found that FAM172A protein expressed moderately in normal tissue, but decreased significantly in colorectal cancer tissue (4). However, the functions of FAM172A on colon cancer cells are unknown, and the regulatory mechanism of its expression remains unclear. In the current study, our results demonstrated that FAM172A inhibited proliferation and promoted apoptosis or differentiation of colon cancer cells. In addition, we cloned the functional promoter variants in FAM172A and presented that the DNA fragment from −112 and +48 of the FAM172A promoter is crucial for its transcription in LoVo cells. Above all, we elaborated the interaction between transcription factors STAT1 and FAM172A promoter in regulating expression of FAM172A. These findings contribute to clarification of the regulatory mechanisms of FAM172A transcription...