{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FLJ22447 is a long non‐coding RNA that appears to play context‐dependent roles in cancer progression. In esophageal squamous cell carcinoma (ESCC) and gastric cancer (GC), FLJ22447 expression is reduced in tumor tissues compared to adjacent non‐tumor tissues, and its low levels are strongly correlated with increased expression of HIF1A and VEGF. These findings suggest that FLJ22447 may normally act to modulate hypoxia and angiogenesis signaling pathways, potentially restraining tumor cell proliferation and vascularization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Conversely, in the tumor microenvironment of oral squamous cell carcinoma (OSCC), FLJ22447 (also referred to as LncRNA‐CAF) is markedly up‐regulated in cancer-associated fibroblasts (CAFs). In this setting, FLJ22447 exerts a pro-tumorigenic role by up-regulating and stabilizing the cytokine interleukin-33 (IL-33). Mechanistically, FLJ22447 prevents the autophagy-lysosome–dependent degradation of IL-33, thereby sustaining high levels of IL-33, which in turn promotes fibroblast activation and enhances tumor cell proliferation. FLJ22447’s interactions with hub proteins known to mediate proliferation, apoptosis, and angiogenesis further underscore its multifaceted role in reprogramming the tumor stroma and facilitating cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies highlight that FLJ22447 can function both as a modulator of key oncogenic pathways involving hypoxia and vascular growth factors in tumor cells as well as a driver for stromal reprogramming via stabilization of IL-33 in CAFs. Its context-dependent effects on tumor microenvironment interactions and cellular homeostasis make FLJ22447 a promising candidate for further investigation as a potential therapeutic target in cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shabbou Bahramian, Reza Sahebi, Zahra Roohinejad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Low expression of LncRNA-CAF attributed to the high expression of HIF1A in esophageal squamous cell carcinoma and gastric cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-021-06882-0"}], "href": "https://doi.org/10.1007/s11033-021-06882-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35040008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35040008"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Liang Ding, Jing Ren, Dongya Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel stromal lncRNA signature reprograms fibroblasts to promote the growth of oral squamous cell carcinoma via LncRNA-CAF/interleukin-33."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgy006"}], "href": "https://doi.org/10.1093/carcin/bgy006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29346528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29346528"}]}]}]}