{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KLHDC7B, a protein characterized by a Kelch domain, has emerged as a multifaceted player in cancer biology. In breast cancer, for example, KLHDC7B is paradoxically upregulated despite promoter hypermethylation and its expression correlates with poorer differentiation and high proliferative indices, with related long non‐coding RNAs—such as LncKLHDC7B and STAR1—not only modulating its transcription but also promoting apoptosis and suppressing cell migration and invasion in triple‐negative cases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In addition, KLHDC7B has been incorporated into prognostic gene signatures across diverse malignancies. In breast cancer and laryngeal carcinoma, its elevated expression aids in risk stratification and associates with unfavorable clinical outcomes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "; in pancreatic adenocarcinoma and bladder cancer, higher KLHDC7B levels similarly contribute to prognostic models."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": " Functionally, KLHDC7B is induced in response to cellular stress. In models of toxin‐induced endoplasmic reticulum stress, its increased expression facilitates apoptotic signaling via regulation of pro‐apoptotic factors such as HRK"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", while in hepatocytes its expression supports hepatitis C virus replication."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Furthermore, alternative splicing events affecting KLHDC7B have been identified in cervical squamous cell carcinoma, where they correlate with tumor size and differentiation status."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Finally, regulatory transcripts divergent from the KLHDC7B locus, such as KLHDC7B-DT, have been shown to modulate the tumor microenvironment in pancreatic cancer by enhancing IL-6 transcription and activating STAT3 signaling that in turn drives macrophage M2 polarization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Collectively, these findings underscore the diverse roles of KLHDC7B in modulating apoptosis, proliferation, invasion, and inflammatory signaling in cancer, highlighting its potential as both a prognostic biomarker and a therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tae Woo Kim, Yoo Jung Kim, Hyun Ji Lee, et al. 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