Lefty-1 inhibits renal epithelial–mesenchymal transition by antagonizing the TGF-β/Smad signaling pathway

Zhang, Lijun; Liu, Xiaohua; Liang, Jun; Wu, Jianhua; Tan, Daqing; Hu, Wei

doi:10.1007/s10735-020-09859-8

Cited by 10 publications

(4 citation statements)

References 42 publications

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“…Lefty-1 can inhibit epithelial–mesenchymal transition and renal interstitial fibrosis by restraining the TGF- β /Smad pathway [ 25 ]. It has been demonstrated that overexpression of LIN28A boosts the invasion and proliferation of colon cancer cells [ 26 , 27 ]; overexpression of LHX3 boosts the migration and invasion of tumor cells [ 28 ]. The overexpression of ST8SIA3 increases cell proliferation, migration, clone formation, and tumor growth of A2B5+ cells from human glioblastoma in vitro [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Construction of Endometrial Carcinoma ceRNA Network and Screening of Key Genes Based on TCGA Database

Song

Chu

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. Long noncoding RNA (lncRNA) has received more and more attention in human tumor research. This study is aimed at clarifying the regulatory network of lncRNAs-microRNAs- (miRNAs-) mRNAs and at determining the relevant targets in the development of endometrial cancers. Methods. Download the miRNA, mRNA, and lncRNA expression profile data of endometrial cancer patients from TCGA; use the “DESeq2” package of R software to identify the differential expression of miRNAs, mRNAs, and lncRNAs; construct a network of ceRNA; and perform gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment assessment on mRNAs in the network of ceRNA; string and Cytoscape 3.7.2 perform PPI assessment on target genes and TOP 10 hub gene screening; Cytoscape 3.7.2 computer program was employed for constructing the lncRNA-miRNA-TOP10 hub mRNA network diagram to determine the signal axis; StarBase database to verify the Top10 hub mRNA expression; the “survival” package in R computer program was implemented to analyze the survival rate of all genes on the lncRNA-miRNA-Top10 hub mRNA network diagram; RT-qPCR to verify the expression level of genes on the signal axis. Results. 1119 differential mRNAs, 14 differential lncRNAs, and 65 differential miRNAs were screened in TCGA; we constructed a ceRNA regulatory network composed of 5 DELs, 7 DEMs, and 90 DEGs; String combined with Cytoscape to screen out Top10 hub genes, namely: LEFTY1, LIN28A, LHX3, ST8SIA3, CEP55, FBXO32, DCN, ANGPTL1, ADRA1A, and KCNMA1; the StarBase database verification results show that ADRA1A, ANGPTL1, FBXO32, KCNMA1, and DCN are downregulated in endometrial cancer tissues; LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 are upregulated in endometrial cancer; the constructed lncRNA-miRNA-hub Top10 mRNA network map identified CTD-2314B22, RP11-89 K21/hsa-miR-143, hsa-miR-424/LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 signal axis; survival analysis results show that CTD-2314B22, RP11-89 K21, hsa-miR-96, hsa-miR-211, LHX3, ST8SIA3, and DCN are all related to survival; RT-qPCR results indicate CTD-2314B22, RP11-89 K21, LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 are upregulated in endometrial cancer cells, and hsa-miR-143 and hsa-miR-424 are downregulated in endometrial cancer cells. Conclusion. From the perspective of the lncRNA-miRNA-mRNA network, our study identified CTD-2314B22, RP11-89 K21/hsa-miR-143, hsa-miR-424/LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 signal axis, which can present considerably potent biomarkers and therapeutic targets for treating endometrial cancer.

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Section: Discussionmentioning

confidence: 99%

Construction of Endometrial Carcinoma ceRNA Network and Screening of Key Genes Based on TCGA Database

Song

Chu

et al. 2022

Computational and Mathematical Methods in Medicine

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“…The serine/threonine kinase activity of the TGF-β Type I receptor stimulates the phosphorylation and activates the Smad signal pathway (Smad 2 and Smad 3). This achieves the biosynthesis of new cells [ 168 , 169 , 170 , 171 , 172 ]. Liang et al [ 172 ] reports the reduction in skin aging with collagen hydrolysate through upregulation of Type I mRNA, III mRNA, and TβRII through activation of Smad signaling pathways.…”

Section: Receptors-based Collagenmentioning

confidence: 99%

Developments for Collagen Hydrolysate in Biological, Biochemical, and Biomedical Domains: A Comprehensive Review

et al. 2021

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The collagen hydrolysate, a proteinic biopeptide, is used for various key functionalities in humans and animals. Numerous reviews explained either individually or a few of following aspects: types, processes, properties, and applications. In the recent developments, various biological, biochemical, and biomedical functionalities are achieved in five aspects: process, type, species, disease, receptors. The receptors are rarely addressed in the past which are an essential stimulus to activate various biomedical and biological activities in the metabolic system of humans and animals. Furthermore, a systematic segregation of the recent developments regarding the five main aspects is not yet reported. This review presents various biological, biochemical, and biomedical functionalities achieved for each of the beforementioned five aspects using a systematic approach. The review proposes a novel three-level hierarchy that aims to associate a specific functionality to a particular aspect and its subcategory. The hierarchy also highlights various key research novelties in a categorical manner that will contribute to future research.

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“…The transforming growth factor-beta (TGF-β) superfamily is a multifunctional family of cytokines, including three specific genes encoding three different TGF-β isoforms (TGF-β1–β3) [ 14 ]. The TGF-βs are known as profibrotic cytokines, which cause tissue fibrosis and regulate the synthesis of ECM proteins involved in fibrosis in different tissues [ 5 , 15 , 16 , 17 ]. In the human eye, the TGF-β family may play a role in glaucoma by regulating collagen synthesis and causing tissue fibrosis, which participates in fibrotic glaucomatous pathologies in the TM, resulting in IOP elevation [ 18 ] via both canonical and noncanonical pathways [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Fibrotic Response of Human Trabecular Meshwork Cells to Transforming Growth Factor-Beta 3 and Autotaxin in Aqueous Humor

et al. 2022

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This study examines the potential role of transforming growth factor-beta 3 (TGF-β3) on the fibrotic response of cultured human trabecular meshwork (HTM) cells. The relationships and trans-signaling interactions between TGF-β3 and autotaxin (ATX) in HTM cells were also examined. The levels of TGF-β and ATX in the aqueous humor (AH) of patients were measured by an immunoenzymetric assay. The TGF-β3-induced expression of the fibrogenic markers, fibronectin, collagen type I alpha 1 chain, and alpha-smooth muscle actin, and ATX were examined by quantitative real-time PCR, Western blotting, and immunocytochemistry, and the trans-signaling regulatory effect of TGF-β3 on ATX expression was also evaluated. In HTM cells, the significant upregulation of ATX was induced by TGF-β3 at a concentration of 0.1 ng/mL, corresponding to the physiological concentration in the AH of patients with exfoliative glaucoma (XFG). However, higher concentrations of TGF-β3 significantly suppressed ATX expression. TGF-β3 regulated ATX transcription and signaling in HTM cells, inducing the upregulation of fibrogenic proteins in a dose-dependent manner. Trans-signaling of TGF-β3 regulated ATX transcription, protein expression, and signaling, and was thereby suggested to induce fibrosis of the trabecular meshwork. Modulation of trans-signaling between TGF-β3 and ATX may be key to elucidate the pathology of XFG, and for the development of novel treatment modalities.

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Lefty-1 inhibits renal epithelial–mesenchymal transition by antagonizing the TGF-β/Smad signaling pathway

Cited by 10 publications

References 42 publications

Construction of Endometrial Carcinoma ceRNA Network and Screening of Key Genes Based on TCGA Database

Construction of Endometrial Carcinoma ceRNA Network and Screening of Key Genes Based on TCGA Database

Developments for Collagen Hydrolysate in Biological, Biochemical, and Biomedical Domains: A Comprehensive Review

Fibrotic Response of Human Trabecular Meshwork Cells to Transforming Growth Factor-Beta 3 and Autotaxin in Aqueous Humor

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