Transcriptomic and functional analysis of ANGPTL4 overexpression in pancreatic cancer nominates targets that reverse chemoresistance

Gordon, Emily R.; Wright, Carter A; James, Mikayla; Cooper, Sara J.

doi:10.21203/rs.3.rs-2444404/v1

Cited by 2 publications

(1 citation statement)

References 42 publications

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“…ANGPTL4 has been recurrently highlighted in numerous studies for its role in highly aggressive oncogenic processes, including EMT, chemoresistance, anoikis resistance and metabolic reprogramming [110,112,191,196,197]. These ANGPTL4-mediated activities could empower cancer cells with metastatic capabilities.…”

Section: Angptl4 Deficiency Attenuates Emt-augmented Chemoresistancementioning

confidence: 99%

Mechanoregulation of angiopoietin-like 4 in epithelial-mesenchymal transition and cancer metastasis

Liao

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The contributions of the co-authors are as follows:• I performed the RNA-seq and microarray data mining, quality control of RNA-seq data, processing of raw RNA-seq data into unified FeatureCounts files for bioinformatics analysis, analysis of RNA-seq data, generation of new RNA-seq data (3D cultured MKN74 cells), characterization of cancer cell spheroids, characterization of 3D collagen-alginate and PEGDA-GelMA cultures, cell imaging, most of the qPCR works, most of the dose response studies, identification of DNAse I hypersensitive regions in human Angptl4 gene, qChIP and animal studies.• H.S. Cheng wrote the codes for RNA-seq data analysis and provided mentorship to me whenever necessary.• J.J.H. Lim performed the experiments on bladder cancer cells and mined the cancer clinical data from databases as part of his undergraduate final year project.• J.X.T. Lee generated the RNA-seq data for 2D cultured MKN74 cells.• M.I.G. Vos and Y.S. Yip provided support to me for animal studies and imaging.• J.J.H. Lim and D. Chua performed the immunoblots.• D. Chua also performed the re-ChIP and zymography.• C.B. Too performed the ASO knockdown and assisted in the imaging of MKN74 spheroids.

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Section: Angptl4 Deficiency Attenuates Emt-augmented Chemoresistancementioning

confidence: 99%

Mechanoregulation of angiopoietin-like 4 in epithelial-mesenchymal transition and cancer metastasis

Liao

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The ANGPTL4-HIF-1α loop: a critical regulator of renal interstitial fibrosis

Li,

Chen,

Yang

et al. 2024

J Transl Med

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Background Renal interstitial fibrosis (RIF) is a progressive, irreversible terminal kidney disease with a poor prognosis and high mortality. Angiopoietin-like 4 (ANGPTL4) is known to be associated with fibrosis in various organs, but its impact on the RIF process remains unclear. This study aimed to elucidate the role and underlying mechanisms of ANGPTL4 in the progression of RIF. Methods In vivo, a chronic kidney disease (CKD) rat model of renal interstitial fibrosis was established via intragastric administration of adenine at different time points (4 and 6 weeks). Blood and urine samples were collected to assess renal function and 24-h urinary protein levels. Kidney tissues were subjected to HE and Masson staining for pathological observation. Immunohistochemistry and real-time quantitative PCR (qRT‒PCR) were performed to evaluate the expression of ANGPTL4 and hypoxia-inducible factor-1α (HIF-1α), followed by Pearson correlation analysis. Subsequently, kidney biopsy tissues from 11 CKD patients (6 with RIF and 5 without RIF) were subjected to immunohistochemical staining to validate the expression of ANGPTL4. In vitro, a fibrosis model of human renal tubular epithelial cells (HK2) was established through hypoxic stimulation. Subsequently, an HIF-1α inhibitor (2-MeOE2) was used, and ANGPTL4 was manipulated using siRNA or plasmid overexpression. Changes in ANGPTL4 and fibrosis markers were analyzed through Western blotting, qRT‒PCR, and immunofluorescence. Results ANGPTL4 was significantly upregulated in the CKD rat model and was significantly positively correlated with renal injury markers, the fibrotic area, and HIF-1α. These results were confirmed by clinical samples, which showed a significant increase in the expression level of ANGPTL4 in CKD patients with RIF, which was positively correlated with HIF-1α. Further in vitro studies indicated that the expression of ANGPTL4 is regulated by HIF-1α, which in turn is subject to negative feedback regulation by ANGPTL4. Moreover, modulation of ANGPTL4 expression influences the progression of fibrosis in HK2 cells. Conclusion Our findings indicate that ANGPTL4 is a key regulatory factor in renal fibrosis, forming a loop with HIF-1α, potentially serving as a novel therapeutic target for RIF.

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Transcriptomic and functional analysis of ANGPTL4 overexpression in pancreatic cancer nominates targets that reverse chemoresistance

Cited by 2 publications

References 42 publications

Mechanoregulation of angiopoietin-like 4 in epithelial-mesenchymal transition and cancer metastasis

Mechanoregulation of angiopoietin-like 4 in epithelial-mesenchymal transition and cancer metastasis

The ANGPTL4-HIF-1α loop: a critical regulator of renal interstitial fibrosis

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