Photodynamic therapy-triggered nuclear translocation of berberine from mitochondria leads to liver cancer cell death

Genome Instability & Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

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Wnt/β-catenin/HNF4α feedback loop facilitates colorectal tumorigenesis and malignancy

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 6, 2025

Background: The Wnt/β-catenin signaling pathway is a central regulator of colorectal cancer (CRC) development, yet its downstream targets and mechanistic contributions to tumorigenesis remain poorly defined. Hepatocyte nuclear factor 4 alpha (HNF4α), transcription primarily studied in liver function hepatocarcinogenesis, has unclear roles CRC. This study investigates the interplay between HNF4α carcinogenesis explores clinical relevance. Methods: Using bulk RNA sequencing (RNA-seq), single-cell (scRNA-seq), vitro vivo CRC models, tumor samples, we assessed expression regulation by signaling. Transcriptional activation was evaluated via luciferase reporter assays chromatin immunoprecipitation. Clinical correlations levels activity were analyzed using immunohistochemistry, sequencing, Spearman’s rank correlation. Statistical significance determined Student’s t-test ANOVA. Results: HNF4α significantly overexpressed tissues compared normal controls promoted growth subcutaneous xenograft models nude mice. Mechanistically, transcriptionally activated Wnt/β-catenin/TCF7L1 axis, forming positive feedback loop that amplified oncogenic Wnt Clinically, strongly correlated with patient samples (r = 0.58, p < 0.0001). Functionally, knockdown suppressed cell proliferation inhibited Wnt-driven tumorigenesis. Conclusions: identifies as novel effector critical driver progression. Wnt/β-catenin/HNF4α uncovered here provides insights into highlights potential therapeutic target. These findings may inform strategies disrupt hyperactivation

Language: Английский

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Modulation of m ⁶ A RNA modification by DAP3 in cancer cells

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(40)

Published: Sept. 24, 2024

N 6 -methyladenosine (m A) RNA methylation is a prevalent modification that significantly impacts metabolism and cancer development. Maintaining the global m A levels in cells relies on accessibility to methyltransferases availability of methyl donor S-adenosylmethionine (SAM). Here, we reveal death associated protein 3 (DAP3) plays crucial role preserving through two distinct mechanisms. First, although DAP3 not component writer complex, it directly binds target regions, thereby facilitating METTL3 binding. Second, promotes MAT2A ’s last intron splicing, increasing protein, cellular SAM, levels. Silencing hinders tumorigenesis, which can be rescued by overexpression. This evidence suggests DAP3’s partly regulation. Our findings unveil complex as an RNA-binding tumor promoter, impacting processing, transcriptomes.

Language: Английский

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HNF4α is a target of the Wnt/β-catenin pathway and regulates colorectal carcinogenesis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 28, 2024

Abstract Hepatocyte nuclear factor 4alpha (HNF4α) is a transcription involved in liver function. Dysregulation of HNF4α leads to hepatocarcinogenesis. However, the role and mechanism colorectal cancer still unknown. Here we demonstrate that upregulated cancers. upregulation promotes tumorigenesis. Notably, expression levels are positively correlated with Wnt/β-catenin signaling pathway patients. Further, showed transcriptionally activated by Wnt/β-catenin/TCF3 at least partially responsible for oncognesis activity Wnt cancer. Our findings indicate direct target could play an important carcinogenesis. Author Summary cancers level

Language: Английский

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