Regulation of Notch1 Signalling by Long Non-Coding RNAs in Cancers and Other Health Disorders

Kałafut, Joanna; Czerwonka, Arkadiusz; Dudziak, Karolina; Przybyszewska-Podstawka, Alicja; Hermanowicz, Justyna Magdalena; Rivero-Müller, Adolfo; Borkiewicz, Lidia

doi:10.3390/ijms241612579

Cited by 2 publications

(2 citation statements)

References 157 publications

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“…When Notch protein interacts with membrane-bound ligands, the protein (Notch) is released from its location, and the Notch translocation to the nucleus is promoted. In the cell nucleus, Notch attaches to DNA sequences in the promoter region of a broad array of genes working as a transcription factor (Kałafut et al, 2023). In mammalian skin cells, the Notchmediated signaling pathway triggers a vital tumor-suppressing and pro-differentiation function (Kałafut et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

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The aryl hydrocarbon receptor (AhR) activation mediates benzo(a)pyrene‐induced overexpression of AQP3 and Notch1 in HaCaT cells

Almendarez‐Reyna,

de la Trinidad Chacón,

Ochoa‐Martínez

et al. 2023

Environ and Mol Mutagen

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The aim of this study was twofold: (1) evaluate the effect of benzo[a]pyrene (BaP) on expression levels of AQP3 and Notch1 genes in HaCaT cells exposed “in vitro” and (2) investigate the possible biological role of assessed genes by bioinformatics methods. Cells were exposed to increasing concentrations of BaP (0.0–4.0 μM) for 1–4 days. After treatments, cell viability and expression levels of AhR, CYP1A1, AQP3, and Notch1 genes were evaluated. The possible biological role of assessed genes was evaluated using bioinformatics tools. Low cytotoxicity in HaCaT cells dosed with BaP was detected. A significant overexpression (p < .05) of CYP1A1, AQP3, and Notch1 was found in exposed HaCaT cells. The gene expression upregulation was dependent on AhR activation. The bioinformatics analysis showed that these genes were enriched in related cancer signaling pathways. The findings suggest that AQP3 and Notch1 are upregulated by AhR activation in HaCaT cells exposed to BaP.

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Section: Discussionmentioning

confidence: 99%

“…In the cell nucleus, Notch attaches to DNA sequences in the promoter region of a broad array of genes working as a transcription factor (Kałafut et al, 2023). In mammalian skin cells, the Notchmediated signaling pathway triggers a vital tumor-suppressing and pro-differentiation function (Kałafut et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

The aryl hydrocarbon receptor (AhR) activation mediates benzo(a)pyrene‐induced overexpression of AQP3 and Notch1 in HaCaT cells

Almendarez‐Reyna,

de la Trinidad Chacón,

Ochoa‐Martínez

et al. 2023

Environ and Mol Mutagen

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SPINK13 acts as a tumor suppressor in hepatocellular carcinoma by inhibiting Akt phosphorylation

Lun,

Sun,

Wei

et al. 2024

Cell Death Dis

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The PI3K/Akt pathway is overexpressed in nearly 50% of hepatocellular carcinomas and inhibits apoptosis by promoting the expression of antiapoptotic genes. Serine protease inhibitors have been shown to induce apoptosis in hepatoma cells by downregulating SPINK13 in the PI3K/Akt pathway. In this study, SPINK13 was expressed in lentiviral vectors. Changes in signaling pathway adapter proteins, apoptosis regulatory proteins, cell cycle regulatory proteins, and the biological behavior of hepatocellular carcinoma were observed in cell and nude mouse xenograft models. The underlying mechanism of endogenous SPINK13-induced apoptosis in hepatocellular carcinoma cells was explored via transcriptomics. As a result, endogenous SPINK13 might inhibit the activity of Furin protease, downregulate the Notch1/Hes1 pathway in a binding manner, activate the direct effector PTEN, inhibit Akt phosphorylation, inactivate the downstream PI3K/Akt pathway, and ultimately lead to mitochondrial apoptosis and cell cycle arrest in hepatoma cells. Therefore, the Notch1/Hes1/PTEN pathway may act upstream of SPINK13 to downregulate the PI3K/Akt signaling pathway. Our study helps elucidate the underlying mechanism of SPINK13 in anti-hepatocellular carcinoma and lays a theoretical foundation for the development of novel therapeutic serine protease inhibitors.

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Regulation of Notch1 Signalling by Long Non-Coding RNAs in Cancers and Other Health Disorders

Cited by 2 publications

References 157 publications

The aryl hydrocarbon receptor (AhR) activation mediates benzo(a)pyrene‐induced overexpression of AQP3 and Notch1 in HaCaT cells

The aryl hydrocarbon receptor (AhR) activation mediates benzo(a)pyrene‐induced overexpression of AQP3 and Notch1 in HaCaT cells

SPINK13 acts as a tumor suppressor in hepatocellular carcinoma by inhibiting Akt phosphorylation

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