TGF-β Signaling in Liver, Pancreas, and Gastrointestinal Diseases and Cancer

Gough, Nancy R.; Xiang, Xiyan; Mishra, Lopa

doi:10.1053/j.gastro.2021.04.064

Cited by 115 publications

(92 citation statements)

References 271 publications

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“…We assigned TGF-β receptor-associated protein 1 (TRAP1), LRG, ubiquitin C-terminal hydrolase 19 (UCH19) and phosphofurin acidic cluster sorting protein 1 (PACS1) to TGF-β signal transduction, which is essential to maintain the homeostasis and normal immune function of the liver, pancreas and gastrointestinal system ( 30 ). The compound formed by TGF-β receptor I (TβR I, also known as activin receptor-like kinase, ALK) and TGF-β receptor II (TβR II) recognizes TGF-β and then phosphorylates the C-termini of the transcription factors Smad2 and Smad3.…”

Section: Discussionmentioning

confidence: 99%

Comparative Metabolomics and Proteomics Reveal Vibrio parahaemolyticus Targets Hypoxia-Related Signaling Pathways of Takifugu obscurus

Yu²,

Ye³

et al. 2022

Front. Immunol.

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Coronavirus disease 2019 (COVID-19) raises the issue of how hypoxia destroys normal physiological function and host immunity against pathogens. However, there are few or no comprehensive omics studies on this effect. From an evolutionary perspective, animals living in complex and changeable marine environments might develop signaling pathways to address bacterial threats under hypoxia. In this study, the ancient genomic model animal Takifugu obscurus and widespread Vibrio parahaemolyticus were utilized to study the effect. T. obscurus was challenged by V. parahaemolyticus or (and) exposed to hypoxia. The effects of hypoxia and infection were identified, and a theoretical model of the host critical signaling pathway in response to hypoxia and infection was defined by methods of comparative metabolomics and proteomics on the entire liver. The changing trends of some differential metabolites and proteins under hypoxia, infection or double stressors were consistent. The model includes transforming growth factor-β1 (TGF-β1), hypoxia-inducible factor-1α (HIF-1α), and epidermal growth factor (EGF) signaling pathways, and the consistent changing trends indicated that the host liver tended toward cell proliferation. Hypoxia and infection caused tissue damage and fibrosis in the portal area of the liver, which may be related to TGF-β1 signal transduction. We propose that LRG (leucine-rich alpha-2-glycoprotein) is widely involved in the transition of the TGF-β1/Smad signaling pathway in response to hypoxia and pathogenic infection in vertebrates as a conserved molecule.

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Section: Discussionmentioning

confidence: 99%

Comparative Metabolomics and Proteomics Reveal Vibrio parahaemolyticus Targets Hypoxia-Related Signaling Pathways of Takifugu obscurus

Yu²,

Ye³

et al. 2022

Front. Immunol.

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“…Moreover, KEGG pathway enrichment analysis suggested that these DE genes were enriched mainly in vascular smooth muscle contraction, focal adhesion, and the TGF beta signaling pathway, and were also closely related to small cell lung cancer, NSCLC, melanoma, glioma, prostate cancer, thyroid cancer, CRC, and other cancers. According to the previous study, the focal adhesion and the TGF beta signaling pathways play essential roles in cell proliferation, and dysregulation of these two pathways is closely associated with oncogenesis [ 27 , 28 ]. In addition, to further verify whether the functional annotations of the DE lncRNAs and mRNAs were basically consistent, we used Venn diagram software to intersect the DE lncRNA target genes and DE mRNAs and found 523 overlapping genes, which were involved mainly in the extracellular matrix, myosin complex, cytoskeleton, and signal transduction, among other processes.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel prognosis-associated ceRNA network in lung adenocarcinoma via bioinformatics analysis

Zhang

et al. 2021

BioMed Eng OnLine

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Background Lung adenocarcinoma (LUAD) is the most common subtype of nonsmall-cell lung cancer (NSCLC) and has a high incidence rate and mortality. The survival of LUAD patients has increased with the development of targeted therapeutics, but the prognosis of these patients is still poor. Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of LUAD. The purpose of this study was to identify novel abnormally regulated lncRNA–microRNA (miRNA)–messenger RNA (mRNA) competing endogenous RNA (ceRNA) networks that may suggest new therapeutic targets for LUAD or relate to LUAD prognosis. Methods We used the SBC human ceRNA array V1.0 to screen for differentially expressed (DE) lncRNAs and mRNAs in four paired LUAD samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the DE lncRNAs and mRNAs. R bioinformatics packages, The Cancer Genome Atlas (TCGA) LUAD database, and Kaplan–Meier (KM) survival analysis tools were used to validate the microarray data and construct the lncRNA–miRNA–mRNA ceRNA regulatory network. Then, quantitative real-time PCR (qRT-PCR) was used to validate the DE lncRNAs in 7 LUAD cell lines. Results A total of 2819 DE lncRNAs and 2396 DE mRNAs (P < 0.05 and fold change ≥ 2 or ≤ 0.5) were identified in four paired LUAD tissue samples. In total, 255 of the DE lncRNAs were also identified in TCGA. The GO and KEGG analysis results suggested that the DE genes were most enriched in angiogenesis and cell proliferation, and were closely related to human cancers. Moreover, the differential expression of ENST00000609697, ENST00000602992, and NR_024321 was consistent with the microarray data, as determined by qRT-PCR validation in 7 LUAD cell lines; however, only ENST00000609697 was associated with the overall survival of LUAD patients (log-rank P = 0.029). Finally, through analysis of ENST00000609697 target genes, we identified the ENST00000609697–hsa-miR-6791-5p–RASL12 ceRNA network, which may play a tumor-suppressive role in LUAD. Conclusion ENST00000609697 was abnormally expressed in LUAD. Furthermore, downregulation of ENST00000609697 and its target gene RASL12 was associated with poor prognosis in LUAD. The ENST00000609697–hsa-miR-6791-5p–RASL12 axis may play a tumor-suppressive role. These results suggest new potential prognostic and therapeutic biomarkers for LUAD.

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“…According to a previous study, the focal adhesion and TGF beta signaling pathways play essential roles in cell proliferation, and dysregulation of these two pathways is closely associated with oncogenesis [29,30]. In addition, to further verify whether the functional annotations of the DE lncRNAs and DE mRNAs were basically consistent, we used Venn diagram software to intersect the DE lncRNA target genes and the DE mRNAs and found 523 overlapping genes, which were involved mainly in the extracellular matrix, myosin complex, cytoskeleton, signal transduction, and so on.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Prognosis-Associated ceRNA Network in Lung Adenocarcinoma via Bioinformatics analysis

Zhang

et al. 2021

Preprint

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Backgroud: Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of lung adenocarcinoma (LUAD). The purpose of this study was to identify novel abnormally regulated lncRNA-microRNA (miRNA)-messenger RNA (mRNA) competing endogenous RNA (ceRNA) networks related to LUAD prognosis.Methods: We programmed an Agilent Microarray Scanner to screen for differentially expressed (DE) lncRNAs and mRNAs in 4 paired LUAD samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the DE lncRNAs and mRNAs. R bioinformatics packages, The Cancer Genome Atlas (TCGA) LUAD database and a Kaplan-Meier (KM) survival analysis tools were used to validate the microarray data and construct the lncRNA-miRNA-mRNA ceRNA regulatory network. Then, quantitative real-time PCR was used to validate the DE lncRNAs in 7 LUAD cell lines.Results: A total of 2819 DE lncRNAs and 2396 DE mRNAs (P-value < 0.05 and fold change ≥2 or ≤0.5) were identified in 4 paired LUAD tissue samples. In total, 255 of these DE lncRNAs were also identified in TCGA. The GO and KEGG analysis results suggested that the DE genes were most enriched in angiogenesis and cell proliferation and closely related to human cancers. Moreover, the differential expression of ENST00000609697, ENST00000602992, and NR_024321 was consistent with the microarray data, as determined by quantitative real-time PCR validation in 7 LUAD cell lines, but only ENST00000609697 was associated with the overall survival of LUAD patients (log-rank P=0.029). Finally, through analysis of ENST00000609697 target genes, we identified the ENST00000609697–hsa-miR-6791-5p–RASL12 ceRNA network, which may play a tumor-suppressive role in LUAD.Conclusion: ENST00000609697 was abnormally expressed in LUAD. Furthermore, downregulation of ENST00000609697 and its target gene RASL12 were associated with poor prognosis in LUAD. The ENST00000609697–hsa-miR-6791-5p–RASL12 axis may play a tumor-suppressive role. These results may suggest new prognostic and therapeutic biomarkers for LUAD.

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TGF-β Signaling in Liver, Pancreas, and Gastrointestinal Diseases and Cancer

Cited by 115 publications

References 271 publications

Comparative Metabolomics and Proteomics Reveal Vibrio parahaemolyticus Targets Hypoxia-Related Signaling Pathways of Takifugu obscurus

Comparative Metabolomics and Proteomics Reveal Vibrio parahaemolyticus Targets Hypoxia-Related Signaling Pathways of Takifugu obscurus

Identification of a novel prognosis-associated ceRNA network in lung adenocarcinoma via bioinformatics analysis

Identification of a Novel Prognosis-Associated ceRNA Network in Lung Adenocarcinoma via Bioinformatics analysis

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