Aftph-KO Mouse

Aftiphilin (AFTPH) is a protein-encoding gene that plays a crucial role in regulating intracellular trafficking, exocytosis, and the pro-inflammatory response [1-3]. It is involved in clathrin-mediated trafficking, interacting with clathrin adaptor proteins AP-1 and AP-2, and localizes to the trans-Golgi network and synapses in neurons [4]. In colonic epithelial cells, it is part of the miR-133α-AFTPH axis regulating neurotensin-associated inflammation [2,3,5].

In different cancers including breast invasive carcinoma (BRCA), diffuse large B-cell lymphoma (DLBC), lung squamous cell carcinoma (LUSC), and pancreatic adenocarcinoma (PAAD), AFTPH shows higher expression in cancer tissues compared to normal tissues. Low AFTPH expression is associated with improved prognosis for these cancer types. Gene copy number gains and amplification of AFTPH are common in these cancers. Transfection of cells with AFTPH siRNA demonstrated its positive effect on cell proliferation in BRCA, LUSC, and PAAD cells, suggesting it may be a potential therapeutic target and prognostic biomarker [1]. In colonic epithelial cells, gene silencing of AFTPH enhanced the neurotensin-induced pro-inflammatory responses, and AFTPH levels were downregulated in experimental colitis [3].

In conclusion, AFTPH is essential for intracellular trafficking, exocytosis, and the regulation of the pro-inflammatory response. In cancer, its expression is associated with prognosis and cell proliferation, and in colonic inflammation, it is involved in the regulation of the inflammatory response. The study of AFTPH in gene-silencing models helps to understand its role in cancer and inflammatory bowel disease, providing potential directions for treatment.

References:

1. Zhu, Tengjiao, Chen, Yingtong, Liu, Zhongjun, Leng, Yuxin, Tian, Yun. 2020. Expression profiles and prognostic significance of AFTPH in different tumors. In FEBS open bio, 10, 2666-2677. doi:10.1002/2211-5463.13003. https://pubmed.ncbi.nlm.nih.gov/33090728/

2. Law, Ivy Ka Man, Jensen, Dane, Bunnett, Nigel W, Pothoulakis, Charalabos. 2016. Neurotensin-induced miR-133α expression regulates neurotensin receptor 1 recycling through its downstream target aftiphilin. In Scientific reports, 6, 22195. doi:10.1038/srep22195. https://pubmed.ncbi.nlm.nih.gov/26902265/

3. Law, Ivy Ka Man, Bakirtzi, Kyriaki, Polytarchou, Christos, Iliopoulos, Dimitrios, Pothoulakis, Charalabos. 2014. Neurotensin--regulated miR-133α is involved in proinflammatory signalling in human colonic epithelial cells and in experimental colitis. In Gut, 64, 1095-104. doi:10.1136/gutjnl-2014-307329. https://pubmed.ncbi.nlm.nih.gov/25112884/

4. Burman, Jonathon L, Wasiak, Sylwia, Ritter, Brigitte, de Heuvel, Elaine, McPherson, Peter S. . Aftiphilin is a component of the clathrin machinery in neurons. In FEBS letters, 579, 2177-84. doi:. https://pubmed.ncbi.nlm.nih.gov/15811338/

5. Law, Ivy Ka Man, Pothoulakis, Charalabos. . MicroRNA-133α regulates neurotensin-associated colonic inflammation in colonic epithelial cells and experimental colitis. In RNA & disease (Houston, Tex.), 2, . doi:. https://pubmed.ncbi.nlm.nih.gov/26005712/