{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cyclin J (CCNJ) has emerged as an important regulator of cell cycle progression and mitosis that is frequently modulated in human cancers. In breast cancer, CCNJ is a direct target of the tumor‐suppressive microRNA miR‐125b, and its knockdown mirrors the growth‐inhibitory effects of miR‐125b overexpression, thereby contributing to cell cycle arrest at the G2/M checkpoint."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In bladder cancer, cyclin J is similarly targeted by miR‐205, which reduces cell proliferation, migration, and invasion, implying that CCNJ normally acts to promote cell cycle progression and that its suppression can have therapeutic effects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In prostate cancer cells, vitamin D–induced miR‐98 down‐regulates CCNJ, a protein critical for mitotic control, leading to G2/M arrest and inhibition of tumor cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Furthermore, in ErbB-2–positive breast and gastric cancers, miR‐16 targets CCNJ among other genes; its enforced expression contributes to an antiproliferative effect, further implicating CCNJ in driving oncogenic proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In hepatocellular carcinoma, CCNJ was identified by a triple combination array approach as a candidate cancer-related gene; its promoter hypermethylation was associated with reduced expression and poorer overall survival, suggesting that abnormal regulation of CCNJ can serve as a prognostic marker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Additionally, beyond its classical role in cell cycle control, cyclin J has been implicated in the regulation of cellular metabolism in inflammatory macrophages, where CCNJ-dependent signaling modulates transcription factors and mitochondrial dynamics, thus influencing both cytokine production and antitumor immunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In experimental therapeutic settings, manipulation of microRNAs targeting CCNJ—such as with miR‐125b delivered alongside other agents—has been shown to inhibit tumor cell proliferation, underscoring the oncogenic potential of CCNJ when not properly suppressed."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, research in bladder cancer indicates that upstream factors such as brain-derived neurotrophic factor can indirectly enhance CCNJ expression by inhibiting miR-205, thereby promoting cell proliferation; this further exemplifies the complexity of CCNJ regulation in oncogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, updated classifications of cyclins have included CCNJ as an atypical cyclin based on its structural features and interactions with cyclin-dependent kinases, reinforcing its distinctive role in the orchestration of cell division."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andrea Feliciano, Josep Castellvi, Ana Artero-Castro, et al. 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