{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nComplex cytokine signaling networks critically influence diverse immunological and pathological processes. For instance, one study revealed that a novel secreted complex consisting of p28 and cytokine‐like factor 1 (CLF) can modulate natural killer and T cell functions through engagement of both the IL-27 and IL-6 receptors, highlighting the intricate interplay between cytokine subunits and receptor components in immune regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In a related context, research in osteoarthritis has demonstrated that cytokine receptor-like factor 1 (CRLF1) is markedly upregulated in degenerative cartilage, implicating this molecule in the joint’s inflammatory processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast with these extracellular signaling events, emerging evidence emphasizes the pivotal role of microRNAs in cancer biology. Notably, mir-4746 has been identified in colorectal cancer (CRC) as a tumor-suppressive molecule. Its expression is significantly down-regulated in CRC tissues and cells, a reduction that correlates with larger tumor size and poorer patient prognosis. Functional studies indicate that mir-4746 directly targets the 3’-untranslated region of the CCND1 mRNA, thereby enhancing its degradation. This reduction in CCND1 levels results in an arrest of the cell cycle at the G0-G1 phase and ultimately impairs CRC cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther highlighting the complexity of cytokine-related pathways in disease contexts, another investigation has shown that CRLF1 also contributes to pathological cardiac remodeling. In models of myocardial infarction, CRLF1 was found to be predominantly expressed in cardiac fibroblasts and to exacerbate fibrosis through activation of the ERK1/2 signaling cascade."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Together, these studies underscore how diverse molecular regulators—from cytokine complexes to microRNAs such as mir-4746—play distinct yet interconnected roles in controlling cellular proliferation, differentiation, and fibrotic responses, with mir-4746 emerging as a promising candidate for prognostic evaluation and therapeutic targeting in colorectal cancer.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sandrine Crabé, Angélique Guay-Giroux, Aurélie Jeanne Tormo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The IL-27 p28 subunit binds cytokine-like factor 1 to form a cytokine regulating NK and T cell activities requiring IL-6R for signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0901464"}], "href": "https://doi.org/10.4049/jimmunol.0901464"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19933857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19933857"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hao Xu, Changrong Ding, Cuicui Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of CRLF1 promotes the chondrogenic differentiation of bone marrow-derived mesenchymal stem and protects cartilage tissue from damage in osteoarthritis via activation of miR-320."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s10020-021-00369-1"}], "href": "https://doi.org/10.1186/s10020-021-00369-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34551709"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34551709"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yuehan Ren, Yun Li, Weiguang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mir-4746 inhibits the proliferation of colorectal cancer cells in vitro and in vivo by targeting CCND1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2022.01.063"}], "href": "https://doi.org/10.1016/j.bbrc.2022.01.063"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35085892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35085892"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shenjian Luo, Zhi Yang, Ruxin Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Zhejiang Univ Sci B (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1631/jzus.B2200506"}], "href": "https://doi.org/10.1631/jzus.B2200506"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37551555"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37551555"}]}]}]}