TGF-β1/Smad3 upregulates UCA1 to promote liver fibrosis through DKK1 and miR18a

Yang, Zhangshuo; Zhang, Hao; Yin, Maohui; Cheng, Zhixiang; Jiang, Ping; Feng, Maohui; Liu, Zhisu; Liao, Bo

doi:10.1007/s00109-022-02248-6

Cited by 12 publications

(13 citation statements)

References 39 publications

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“…According to the published articles, increasing evidence has demonstrated the underlying mechanisms and functions of lncRNAs at multiple regulatory levels 42 . Many existing articles indicated that UCA1 acts as a microRNA (miRNA) sponge 43–46 . Under this mechanism, UCA1 functions as an endogenous mimic target of miRNAs, resulting in the regulation of mRNA which is affected by miRNAs.…”

Section: Discussionmentioning

confidence: 99%

“…42 Many existing articles indicated that UCA1 acts as a microRNA (miRNA) sponge. [43][44][45][46] Under this mechanism, UCA1 functions as an endogenous mimic target of miRNAs, resulting in the regulation of mRNA which is affected by miRNAs. Nevertheless, numerous studies fall short of identifying the targeted miRNA or the location of UCA1, with substantial miRNA data retrieved from databases.…”

Section: Discussionmentioning

confidence: 99%

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lncRNA UCA1 promotes tumor progression by targeting SMARCD3 in cervical cancer

An,

Dong,

Chi

et al. 2023

Molecular Carcinogenesis

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Long noncoding RNA urothelial carcinoma associated 1 (UCA1) has been identified as a key molecule in human cancers. However, its functional implications remain unspecified in the context of cervical cancer (CC). This research aims to identify the regulatory mechanism of UCA1 in CC. UCA1 was identified through microarray and confirmed through a quantitative real‐time polymerase chain reaction. Proteins that bind with UCA1 were recognized using RNA pull‐down assays along with RNA immunoprecipitation. Ubiquitination assays and coimmunoprecipitation were performed to explore the molecular mechanisms of the SWI/SNF‐related, matrix‐associated, actin‐dependent regulator of chromatin, subfamily d, member 3 (SMARCD3) downregulated in CC. The effects of UCA1 and SMARCD3 on the progression of CC were investigated through gain‐ and loss‐of‐function assays and xenograft tumor formation in vivo. In this study, UCA1 was found to be upregulated in CC cells as well as in human plasma exosomes for the first time. Functional studies indicated that UCA1 promotes CC progression. Mechanically, UCA1 downregulated the SMARCD3 protein stabilization by promoting SMARCD3 ubiquitination. Taken together, we revealed that the UCA1/SMARCD3 axis promoted CC progression, which could provide a new therapeutic target for CC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

lncRNA UCA1 promotes tumor progression by targeting SMARCD3 in cervical cancer

An,

Dong,

Chi

et al. 2023

Molecular Carcinogenesis

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“…The control plasmid, Flag-KIF18A, HA-TTC3, His-UB, and MYC–AKT plasmids were created by TSINGKE. As previously mentioned, plasmid transfection was carried out using lipofectamine 3000 (Invitrogen, Carlsbad, CA, USA) [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

KIF18A inactivates hepatic stellate cells and alleviates liver fibrosis through the TTC3/Akt/mTOR pathway

Zhang,

Xia,

Xia

et al. 2024

Cell. Mol. Life Sci.

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Activation of hepatic stellate cells (HSCs) has been demonstrated to play a pivotal role in the process of liver fibrogenesis. In this study, we observed a decrease in the expression of KIF18A in fibrotic liver tissues compared to healthy liver tissues, which exhibited a negative correlation with the activation of HSCs. To elucidate the molecular mechanisms underlying the involvement of KIF18A, we performed in vitro proliferation experiments and established a CCl4-induced liver fibrosis model. Our results revealed that KIF18A knockdown enhanced HSCs proliferation and reduced HSCs apoptosis in vitro. Mouse liver fibrosis grade was evaluated with Masson’s trichrome and alpha-smooth muscle actin (α-SMA) staining. In addition, the expression of fibrosis markers Col1A1, Stat1, and Timp1 were detected. Animal experiments demonstrated that knockdown of KIF18A could promote liver fibrosis, whereas overexpression of KIF18A alleviated liver fibrosis in a CCl4-induced mouse model. Mechanistically, we found that KIF18A suppressed the AKT/mTOR pathway and exhibited direct binding to TTC3. Moreover, TTC3 was found to interact with p-AKT and could promote its ubiquitination and degradation. Our findings provide compelling evidence that KIF18A enhances the protein binding between TTC3 and p-AKT, promoting TTC3-mediated ubiquitination and degradation of p-AKT. These results refine the current understanding of the mechanisms underlying the pathogenesis of liver fibrosis and may offer new targets for treating this patient population.

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“…Gene set enrichment analysis (GSEA) is a widely used computational method that determines whether there is a statistically signi cant difference between two gene groups [42] . The clusterPro ler package [43] [version 3.14.3] was used for GSEA [44] in this study.The pathway with signi cant enrichment results was demonstrated based on net enrichment score (NES), gene ratio, and P value.…”

Section: Gsea Enrichment Analysis Of Biological Functions and Pathway...mentioning

confidence: 99%

Explore the possible pathway of improving liver and heart injury in diabetes nephropathy based on bioinformatics analysis

Yang

Wang

et al. 2023

Preprint

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Background This study explore the possible pathway of MicroRNA-130a, TXNIP, CD44 and TGF-β1 improving liver and heart injury in diabetes nephropathy based on bioinformatics ananlysis.Methods Screening Key Genes Using Bioinformatics Analysis. The biochemical index and serum levels of MicroRNA-130a, TXNIP, CD44 and TGF-β1 were detected and analyzed by Pearson correlation analysis in 100 DN patients and 50 healthy controls. The rats model were randomly divided into two groups. The expression of MicroRNA-130a, TXNIP, CD44 and TGF-β1 in liver and heart and the morphological changes was detected.Results Screening and Analysis of Differentially Expressed Genes MicroRNA-130a and TXNIP, CD44 and TGFBI Involved in diabetes Nephropathy by Bioinformatics Methods. Compared to healthy controls, serum levels of MicroRNA-130a were decreased, while levels of TXNIP, CD44 and TGF-β1 were elevated in DN patients. Moreover, MicroRNA-130a was negatively correlated with TXNIP, CD44 and TGF-β1. In DN rats, the levels of TXNIP, CD44 and TGF-β1 in the liver and heart tissues were significantly elevated, while MicroRNA-130a levels were significantly decreased, compared to the NC group.Conclusion Upregulate MicroRNA-130a and decrease TXNIP, CD44 and TGF-β1 may participate in liver and heart injury pathway of diabetes nephropathy.

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TGF-β1/Smad3 upregulates UCA1 to promote liver fibrosis through DKK1 and miR18a

Cited by 12 publications

References 39 publications

lncRNA UCA1 promotes tumor progression by targeting SMARCD3 in cervical cancer

lncRNA UCA1 promotes tumor progression by targeting SMARCD3 in cervical cancer

KIF18A inactivates hepatic stellate cells and alleviates liver fibrosis through the TTC3/Akt/mTOR pathway

Explore the possible pathway of improving liver and heart injury in diabetes nephropathy based on bioinformatics analysis

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