N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) mitigates the liver fibrosis via WTAP/m6A/Ptch1 axis through Hedgehog pathway

Wei, Anwei; Zhao, Fei; Hao, Aiping; Liu, Bowei; Liu, Zhenzhen

doi:10.1016/j.gene.2021.146125

Cited by 17 publications

(7 citation statements)

References 24 publications

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“…It plays a key role in the epistatic transcriptomic regulation of RNA metabolism as a regulatory subunit of the m6A methyltransferase complex and has an essential role in early embryonic development ,tissue differentiation, differentiation of the embryonic mesoderm and the development of the urogenital system [31,32] , [12]. It involved in the molecular mechanisms of liver brosis progression [33] and promotes cardiomyocyte endoplasmic reticulum (ER) stress and apoptosis in myocardial infarction [34]. WTAP-p16-signaling axis promotes intimal hyperplasia in angioplasty [35].…”

Section: Discussionmentioning

confidence: 99%

Wilms tumor 1 associated protein promotes metastasis and chemo-resistance to oxaliplatin by nuclear factor kappa B pathway in gastric cancer

Liu

Yang

et al. 2023

Preprint

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Background There is now substantial evidence that epigenetic modifications largely contribute to gastric carcinogenesis and metastasis, causing a large number of tumor-related deaths. N6-methyladenosine(m6A) is a modification that adds a methyl group at the N6 position, and Wilms tumor 1 associated protein (WTAP) is an important methylase of m6A. WTAP has been reported to play a role in a variety of tumors. Results In the present study, we found that WTAP was highly expressed in gastric cancer (GC) tissues and cells and promoted migration/invasion of GC cells. WTAP promoted the expression of B-cell lymphoma-2(bcl-2), inhibited the expression of Bax, increased the protein levels of p-IKKα, p65, p-p65 and p-IκBα, promoted the expression of nuclear factor kappa B (NF-κB) pathway, and mediated the resistance of GC cells to the chemotherapeutic drug oxaliplatin (OPX). Interestingly, the NF-κB pathway-specific inhibitor caffeic acid phenethyl ester (CAPE) eliminated OPX resistance generated by WTAP overexpression cells and essentially reduced it to the level of resistance in their control cells. Conclusions In summary, the WTAP/NF-κB/bcl-2 pathway may be critical in promoting GC cell proliferation and OPX resistance development, providing a potential therapeutic target for GC treatment.

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Section: Discussionmentioning

confidence: 99%

Wilms tumor 1 associated protein promotes metastasis and chemo-resistance to oxaliplatin by nuclear factor kappa B pathway in gastric cancer

Liu

Yang

et al. 2023

Preprint

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“…Moreover, WTAP is involved in selective splicing of mRNA and cell cycle regulation [ 48 ]. Wei et al found that AcSDKP could reduce the stability of Ptch1 mRNA by downregulating WTAP expression and ultimately exert anti-fibrotic effects [ 49 ]. A gene on the X chromosome codes for RBMX, a nuclear RNA-binding protein with a length of 43 kDa.…”

Section: Discussionmentioning

confidence: 99%

Significance of methylation-related genes in diagnosis and subtype classification of renal interstitial fibrosis

Zhang¹,

Yang²,

Liu³

et al. 2023

Hereditas

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Background RNA methylation modifications, such as N1-methyladenosine/N6-methyladenosine /N5-methylcytosine (m1A/m6A/m5C), are the most common RNA modifications and are crucial for a number of biological processes. Nonetheless, the role of RNA methylation modifications of m1A/m6A/m5C in the pathogenesis of renal interstitial fibrosis (RIF) remains incompletely understood. Methods Firstly, we downloaded 2 expression datasets from the GEO database, namely GSE22459 and GSE76882. In a differential analysis of these datasets between patients with and without RIF, we selected 33 methylation-related genes (MRGs). We then applied a PPI network, LASSO analysis, SVM-RFE algorithm, and RF algorithm to identify key MRGs. Results We eventually obtained five candidate MRGs (WTAP, ALKBH5, YTHDF2, RBMX, and ELAVL1) to forecast the risk of RIF. We created a nomogram model derived from five key MRGs, which revealed that the nomogram model may be advantageous to patients. Based on the selected five significant MRGs, patients with RIF were classified into two MRG patterns using consensus clustering, and the correlation between the five MRGs, the two MRG patterns, and the genetic pattern with immune cell infiltration was shown. Moreover, we conducted GO and KEGG analyses on 768 DEGs between MRG clusters A and B to look into their different involvement in RIF. To measure the MRG patterns, a PCA algorithm was developed to determine MRG scores for each sample. The MRG scores of the patients in cluster B were higher than those in cluster A. Conclusions Ultimately, we concluded that cluster A in the two MRG patterns identified on these five key m1A/m6A/m5C regulators may be associated with RIF.

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“…N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is an endogenous tetrapeptide with antifibrotic effects. AcSDKP downregulates the expression of the methyltransferase WTAP, leading to a significant decrease in the stability of Ptch1 mRNA in the Hedgehog pathway, which exerts antifibrotic effects [ 106 ]. Chronic hepatitis B (CHB)-related genes such as HLA-DPA1 and HLA-DPB1 are significantly differentially expressed in the tissues of patients with mild and severe HF.…”

Section: M6a Modification In Hepatic Fibrosismentioning

confidence: 99%

RNA methylations in hepatic fibrosis, a gradually emerging new treatment strategy

Cheng

Wang

et al. 2023

Cell Biosci

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Background Hepatic fibrosis (HF) is a pathological process caused by excessive accumulation of extracellular matrix caused by a series of causes, leading to the formation of fiber scar. RNA methylation is a newly discovered epigenetic modification that exists widely in eukaryotes and prokaryotes and plays a crucial role in the pathogenesis of many diseases. Results The occurrence and development of HF are regulated by many factors, including excessive deposition of extracellular matrix, activation of hepatic stellate cells, inflammation, and oxidative stress. RNA methylations of different species have become a crucial regulatory mode of transcript expression, And participate in the pathogenesis of tumors, nervous system diseases, autoimmune diseases, and other diseases. In addition, there are five common types of RNA methylation, but only m6A plays a crucial regulatory role in HF. The pathophysiological regulation of m6A on HF is achieved by the combination of the methylated transferase, demethylated enzyme, and methylated reading protein. Conclusions RNA methylated methyltransferase, demethylase, and reading protein extensively affect the pathological mechanism of HF, which may be a new therapeutic and diagnostic target, representing a new class of therapeutic strategies.

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N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) mitigates the liver fibrosis via WTAP/m6A/Ptch1 axis through Hedgehog pathway

Cited by 17 publications

References 24 publications

Wilms tumor 1 associated protein promotes metastasis and chemo-resistance to oxaliplatin by nuclear factor kappa B pathway in gastric cancer

Wilms tumor 1 associated protein promotes metastasis and chemo-resistance to oxaliplatin by nuclear factor kappa B pathway in gastric cancer

Significance of methylation-related genes in diagnosis and subtype classification of renal interstitial fibrosis

RNA methylations in hepatic fibrosis, a gradually emerging new treatment strategy

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