Publications by authors named "Yating Xu"

10 Publications

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Role of Main RNA Methylation in Hepatocellular Carcinoma: N6-Methyladenosine, 5-Methylcytosine, and N1-Methyladenosine.

Front Cell Dev Biol 2021 30;9:767668. Epub 2021 Nov 30.

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

RNA methylation is considered a significant epigenetic modification, a process that does not alter gene sequence but may play a necessary role in multiple biological processes, such as gene expression, genome editing, and cellular differentiation. With advances in RNA detection, various forms of RNA methylation can be found, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), and 5-methylcytosine (m5C). Emerging reports confirm that dysregulation of RNA methylation gives rise to a variety of human diseases, particularly hepatocellular carcinoma. We will summarize essential regulators of RNA methylation and biological functions of these modifications in coding and noncoding RNAs. In conclusion, we highlight complex molecular mechanisms of m6A, m5C, and m1A associated with hepatocellular carcinoma and hope this review might provide therapeutic potent of RNA methylation to clinical research.
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http://dx.doi.org/10.3389/fcell.2021.767668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671007PMC
November 2021

YTHDF1 promotes mRNA degradation via YTHDF1-AGO2 interaction and phase separation.

Cell Prolif 2022 Jan 25;55(1):e13157. Epub 2021 Nov 25.

School of Basic Medical Sciences, Wuhan University, Wuhan, China.

Objectives: YTHDF1 is known as a m A reader protein, and many researches of YTHDF1 focused on the regulation of mRNA translation efficiency. However, YTHDF1 is also related to RNA degradation, but how YTHDF1 regulates mRNA degradation is indefinite. Liquid-liquid phase separation (LLPS) underlies the formation of membraneless compartments in mammal cells, and there are few reports focused on the correlation of RNA degradation with LLPS. In this research, we focused on the mechanism of YTHDF1 degraded mRNA through LLPS.

Materials And Methods: The CRISPR/Cas9 knock out system was used to establish the YTHDF1 knock out (YTHDF1-KO) cell lines (HEK293 and HeLa) and METTL14 knock out (METTL14-KO) cell line (HEK293). 4SU-TT-seq was used to check the half-life changes of mRNAs. Actinomycin D and qPCR were used to test the half-life changes of individual mRNA. RNA was stained with SYTO RNA-select dye in wild type (WT) and YTHDF1-KO HeLa cell lines. Co-localization of YTHDF1 and AGO2 was identified by immunofluorescence. The interaction domain of YTHDF1 and AGO2 was identified by western blot. Phase separation of YTHDF1 was performed in vitro and in vivo. Fluorescence recovery after photobleaching (FRAP) was performed on droplets as an assessment of their liquidity.

Results: In this research, we found that deletion of YTHDF1 led to massive RNA patches deposited in cytoplasm. The results of 4SU-TT-seq showed that deletion of YTHDF1 would prolong the half-life of mRNAs. Immunofluorescence data showed that YTHDF1 and AGO2 could co-localize in P-body, and Co-IP results showed that YTHDF1 could interact with AGO2 through YT521-B homology (YTH) domain. We confirmed that YTHDF1 could undergo phase separation in vitro and in vivo, and compared with AGO2, YTHDF1 was more important in P-body formation. The FRAP results showed that liquid AGO2 droplets would convert to gel/solid when YTHDF1 was deleted. As AGO2 plays important roles in miRISCs, we also found that miRNA-mediate mRNA degradation is related to YTHDF1.

Conclusions: YTHDF1 recruits AGO2 through the YTH domain. YTHDF1 degrades targeting mRNAs by promoting P-body formation through LLPS. The deletion of YTHDF1 causes the P-body to change from liquid droplets to gel/solid droplets, and form AGO2/RNA patches, resulting in a degradation delay of mRNAs. These findings reveal a previously unrecognized crosstalk between YTHDF1 and AGO2, raising a new sight of mRNA post-transcriptional regulation by YTHDF1.
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http://dx.doi.org/10.1111/cpr.13157DOI Listing
January 2022

Promising Advances in LINC01116 Related to Cancer.

Front Cell Dev Biol 2021 14;9:736927. Epub 2021 Oct 14.

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Long non-coding RNAs (lncRNAs) are RNAs with a length of no less than 200 nucleotides that are not translated into proteins. Accumulating evidence indicates that lncRNAs are pivotal regulators of biological processes in several diseases, particularly in several malignant tumors. Long intergenic non-protein coding RNA 1116 (LINC01116) is a lncRNA, whose aberrant expression is correlated with a variety of cancers, including lung cancer, gastric cancer, colorectal cancer, glioma, and osteosarcoma. LINC01116 plays a crucial role in facilitating cell proliferation, invasion, migration, and apoptosis. In addition, numerous studies have recently suggested that LINC01116 has emerged as a novel biomarker for prognosis and therapy in malignant tumors. Consequently, we summarize the clinical significance of LINC01116 associated with biological processes in various tumors and provide a hopeful orientation to guide clinical treatment of various cancers in future studies.
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http://dx.doi.org/10.3389/fcell.2021.736927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553226PMC
October 2021

The Vital Roles of LINC00662 in Human Cancers.

Front Cell Dev Biol 2021 20;9:711352. Epub 2021 Jul 20.

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Long non-coding RNAs (lncRNAs) play crucial roles in many human diseases, particularly in tumorigenicity and progression. Although lncRNA research studies are increasing rapidly, our understanding of lncRNA mechanisms is still incomplete. The long intergenic non-protein coding RNA 662 (LINC00662) is a novel lncRNA, and accumulating evidence suggests that it is related to a variety of tumors in multiple systems, including the respiratory, reproductive, nervous, and digestive systems. LINC00662 has been shown to be upregulated in malignant tumors and has been confirmed to promote the development of malignant tumors. LINC00662 has also been reported to facilitate a variety of cellular events, such as tumor-cell proliferation, invasion, and migration, and its expression has been correlated to clinicopathological characteristics in patients with tumors. In terms of mechanisms, LINC00662 regulates gene expression by interacting with both proteins and with RNAs, so it may be a potential biomarker for cancer diagnosis, prognosis, and treatment. This article reviews the expression patterns, biological functions, and underlying molecular mechanisms of LINC00662 in tumors.
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http://dx.doi.org/10.3389/fcell.2021.711352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329443PMC
July 2021

Synergistic antifibrotic effects of miR-451 with miR-185 partly by co-targeting EphB2 on hepatic stellate cells.

Cell Death Dis 2020 05 28;11(5):402. Epub 2020 May 28.

State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 211198, Nanjing, China.

Liver fibrosis is a global health problem currently without clinically approved drugs. It is characterized by the excessive accumulation of extracellular matrix (ECM) mainly produced by activated hepatic stellate cells (HSCs). Uncovering the mechanisms underlying the fibrogenic responses in HSCs may have profound translational implications. Erythropoietin-producing hepatocellular receptor B2 (EphB2) is a receptor tyrosine kinase that has been indicated to be a novel profibrotic factor involved in liver fibrogenesis. In the present study, we investigated the effects of miR-451 and miR-185 on the expression of EphB2 and their roles in liver fibrogenesis both in vitro and in vivo. We found that EphB2 upregulation is a direct downstream molecular event of decreased expression of miR-451 and miR-185 in the process of liver fibrosis. Moreover, miR-451 was unexpectedly found to upregulate miR-185 expression at the post-transcriptional level by directly targeting the nuclear export receptor exportin 1 (XPO-1) and synergistically suppress HSCs activation with miR-185. To investigate the clinical potential of these miRNAs, miR-451/miR-185 agomirs were injected individually or jointly into CCl-treated mice. The results showed that coadministration of these agomirs synergistically alleviated liver fibrosis in vivo. These findings indicate that miR-451 and miR-451/XPO-1/miR-185 axis play important and synergistic regulatory roles in hepatic fibrosis partly through co-targeting EphB2, which provides a novel therapeutic strategy for the treatment of hepatic fibrosis.
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http://dx.doi.org/10.1038/s41419-020-2613-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256034PMC
May 2020

Silencing DAPK3 blocks the autophagosome-lysosome fusion by mediating SNAP29 in trophoblast cells under high glucose treatment.

Mol Cell Endocrinol 2020 02 5;502:110674. Epub 2019 Dec 5.

Department of Histology and Embryology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. Electronic address:

Autophagy plays an essential role in gestational diabetes mellitus (GDM). Death-associated protein kinase-3 (DAPK3) regulates a variety of cellular functions; however, the relationship between DAPK3 and autophagy is unknown. In this study, we aim to investigate whether DAPK3 is associated with autophagy in GDM, and we found that DAPK3 was upregulated in the placenta of GDM patients and extravillous trophoblast cells under high-glucose conditions. Silencing DAPK3 decreased the assembly of the STX17-SNAP29-VAMP8 complex, leading to the blockade of autophagosome-lysosome fusion by mediating synaptosomal-associated protein 29 (SNAP29). Moreover, knockdown of DAPK3 ameliorates cell invasion and mediates autophagy in high glucose, and does not alter the expression of autophagy-related genes in normal glucose. Our study demonstrates the significance of DAPK3 in autophagy and GDM, which may provide new insights into the molecular mechanisms regulating trophoblast invasion.
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http://dx.doi.org/10.1016/j.mce.2019.110674DOI Listing
February 2020

CD48 and α7 Nicotinic Acetylcholine Receptor Synergistically Regulate FimH-Mediated Escherichia coli K1 Penetration and Neutrophil Transmigration Across Human Brain Microvascular Endothelial Cells.

J Infect Dis 2019 01;219(3):470-479

Department of Histology and Embryology, School of Basic Medical Sciences, Wuhan University, China.

FimH-mediated bacterial invasion and polymorphonuclear neutrophil (PMN) transmigration across human brain microvascular endothelial cells (HBMECs) are required for the pathogenesis of Escherichia coli meningitis. However, the underlying mechanism remains unclear. This study demonstrated that the TnphoA mutant (22A33) and FimH-knockout mutant (ΔFimH) of E coli strain E44, which resulted in inactivation of FimH, were less invasive and less effective in promoting PMN transmigration than their wild-type strain. FimH protein induced PMN transmigration, whereas calmodulin inhibitor significantly blocked this effect. Moreover, immunofluorescence and co-immunoprecipitation analysis indicated that colocalized CD48 and α7 nAChR formed a complex on the surface of HBMECs that is associated with increased cofilin dephosphorylation, which could be remarkably enhanced by FimH+ E44. Our study concluded that FimH-induced E coli K1 invasion and PMN migration across HBMECs may be mediated by the CD48-α7nAChR complex in lipid rafts of HBMEC via Ca2+ signaling and cofilin dephosphorylation.
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http://dx.doi.org/10.1093/infdis/jiy531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325351PMC
January 2019

Systematic Characterization of Autophagy in Gestational Diabetes Mellitus.

Endocrinology 2017 08;158(8):2522-2532

School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.

Autophagy is a dynamic process that degrades and recycles cellular organelles and proteins to maintain cell homeostasis. Alterations in autophagy occur in various diseases; however, the role of autophagy in gestational diabetes mellitus (GDM) is unknown. In the present study, we characterized the roles and functions of autophagy in GDM patient samples and extravillous trophoblasts cultured with glucose. We found significantly enhanced autophagy in GDM patients. Moreover, high glucose levels enhanced autophagy and cell apoptosis, reducing proliferation and invasion, and these effects were ameliorated through knockdown of ATG5. Genome-wide 5-hydroxymethylcytosine data analysis further revealed the epigenomic regulatory circuitry underlying the induced autophagy and apoptosis in GDM and preeclampsia. Finally, RNA sequencing was performed to identify gene expression changes and critical signaling pathways after silencing of ATG5. Our study has demonstrated the substantial functions of autophagy in GDM and provides potential therapeutic targets for the treatment of GDM patients.
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http://dx.doi.org/10.1210/en.2016-1922DOI Listing
August 2017

Hypercrosslinked strong cation-exchange polymers for selective extraction of serum purine metabolites associated with gout.

Talanta 2016 May 11;151:172-178. Epub 2016 Jan 11.

Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China. Electronic address:

In this study, hypercrosslinked strong cation-exchange polymer resins (HXLPP-SCX) were synthesized and employed as selective sorbents for the solid-phase extraction (SPE) of basic purine metabolites associated with gout. The HXLPP-SCX material was prepared based on hypercrosslinking reactions and sulfonated with concentrated H2SO4. This synthetic procedure is facile and efficient without using highly toxic reagent. The resulting resins were characterized in the form of monodisperse microspheres (mean diameters of 3‒5μm) with narrow pore size (2.1nm) and relatively high specific surface areas (801m(2)/g). The polymers also possess high ion-exchange capacity (IEC, 2.22mmol/g) and good adsorption and selectivity performances for basic compounds. The resins used as SPE sorbents permit the selective enrichment of three pivotal purine metabolites (hypoxanthine, xanthine and inosine) in human serum followed by HPLC analysis. Method validation including linearity range, sensitivity, accuracy and reproducibility were evaluated. This method was exemplarily applied in the analysis of serum purines in gout patients and healthy controls. The present results demonstrate a promising potential of this HXLPP-SCX material for the clinical sample pretreatment.
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http://dx.doi.org/10.1016/j.talanta.2016.01.014DOI Listing
May 2016

Baicalein inhibits migration and invasion of gastric cancer cells through suppression of the TGF-β signaling pathway.

Mol Med Rep 2014 Oct 5;10(4):1999-2003. Epub 2014 Aug 5.

Department of Gastroenterology, Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.

The transforming growth factor-β (TGF-β) signaling pathway exhibits an important role in cancer invasion and metastasis. Excessive expression of TGF-β activates Smad4, leading to the upregulation of downstream metastasis-associated genes. Thus, the inhibition of the TGF-β/Smad4 signaling pathway may be a novel strategy for treatment of cancer metastasis. Baicalein, a flavonoid derived from the root of Scutellaria baicalensis, has been reported to exert strong anti-tumor activity towards various types of cancer. In the present study the effect of baicalein on migration and invasion of cancer cells was evaluated using wound-healing and Transwell assays. In order to investigate the possible molecular mechanisms of the anti-metastatic effects of baicalein, quantitative polymerase chain reaction (qPCR) and western blot analyses were performed to examine the effect on the expression of TGF‑β, Smad4, N-cadherin, vimentin, ZEB1 and ZEB2. It was determined that baicalein inhibited the migration and invasion of AGS cells by suppressing the TGF-β/Smad4 signaling pathway. In addition, baicalein treatment reduced the expression of the metastasis-associated N-cadherin, vimentin, ZEB1 and ZEB2, downstream target genes of the TGF‑β/Smad4 signaling pathway. Collectively, these results suggest that inhibition of the metastasis of cancer cells via inactivation of TGF-β/Smad4 signaling is one of the mechanisms by which baicalein may treat cancer.
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http://dx.doi.org/10.3892/mmr.2014.2452DOI Listing
October 2014
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