Overexpression of YTHDF3 increases the specific productivity of the recombinant protein in CHO cells by promoting the translation process DOI

Zhao‐ming Cui,

Yingying Feng,

Yan‐ping Gao

et al.

Biotechnology Journal, Journal Year: 2024, Volume and Issue: 19(4)

Published: April 1, 2024

Due to their high-quality characteristics, Chinese hamster ovary (CHO) cells have become the most widely used and reliable host for production of recombinant therapeutic proteins in biomedical field. Previous studies shown that m6A reader YTHDF3, which contains YTH domain, can affect a variety biological processes by regulating translation stability target mRNAs. This study investigates effect YTHDF3 on transgenic CHO cells. The results indicate stable overexpression significantly enhances protein expression without affecting cell growth. Transcriptome sequencing indicated several genes, including initiation factor, extension ribosome assembly were upregulated overexpressing YTHDF3. In addition, cycloheximide experiments confirmed enhanced transgene promoting conclusion, findings this provide novel approach mammalian engineering increase productivity m6A.

Language: Английский

USP18 Stabilized FTO Protein to Activate Mitophagy in Ischemic Stroke Through Repressing m6A Modification of SIRT6 DOI Creative Commons
Mingyu Song, Fang Yi, Feiyue Zeng

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(9), P. 6658 - 6674

Published: Feb. 10, 2024

Ischemic stroke (IS) is a dangerous cerebrovascular disorder with significant incidence and death rate. Ubiquitin-specific peptidase 18 (USP18) has been proven to mitigate ischemic brain damage; however, its potential regulatory mechanisms remain unclear. In vivo in vitro models of IS were established by middle cerebral artery occlusion (MCAO) oxygen-glucose deprivation/reoxygenation (OGD/R). Neurocyte injury was detected MTT, LDH, ROS level, mitochondrial membrane (Δψm), flow cytometry. Molecular expression evaluated qPCR, Western blotting, immunofluorescence staining. determined Co-IP, RIP, MeRIP. neurological behavior score TTC Mitophagy observed TEM. USP18 fat mass obesity-associated protein (FTO) declined after OGD/R. Dysfunctional apoptosis OGD/R-stimulated neurocytes eliminated USP18/FTO overexpression via mitophagy activation. USP18-mediated de-ubiquitination responsible for increasing FTO stability. Up-regulation restrained m6A modification sirtuin6 (SIRT6) YTHDF2-dependent manner enhance SIRT6 subsequent activation AMPK/PGC-1α/AKT signaling. induced ameliorate nerve cell damage through SIRT6/AMPK/PGC-1α/AKT pathway. Finally, relieved rats triggering axis-mediated mitophagy. increased stability trigger SIRT6-induced mitophagy, thus mitigating IS. Our data unravel the novel neuroprotective mechanism suggest as promising treatment target

Language: Английский

Citations

10
FTO Deficiency Alleviates LPS-induced Acute Lung Injury by TXNIP/NLRP3-mediated Alveolar Epithelial Cell Pyroptosis DOI

Wei-Ming Xie,

Wei Su,

Xinyu Liu

et al.

American Journal of Respiratory Cell and Molecular Biology, Journal Year: 2024, Volume and Issue: 70(5), P. 351 - 363

Published: Jan. 25, 2024

N6-methyladenosine (m6A) plays a role in various diseases, but it has rarely been reported acute lung injury (ALI). The fat mass and obesity-associated (FTO) protein can regulate mRNA metabolism by removing m6A residues. This study aimed to examine the mechanism of demethylase FTO lipopolysaccharide (LPS)-induced ALI. Lung epithelial knockout mice knockdown/overexpression A549 cell lines were constructed evaluate effects on Bioinformatics analysis series vivo vitro assays used regulation. Rescue conducted whether impact ALI depended TXNIP/NLRP3 pathway. In LPS-induced ALI, RNA modification levels upregulated, expression was downregulated. vivo, alleviated alveolar structure disorder, tissue oedema, pulmonary inflammation improved survival mice. vitro, knockdown reduced damage death induced LPS, while overexpression exacerbated death. Mechanistically, bioinformatics revealed that TXNIP downstream target FTO. deficiency mitigated pyroptosis via confirmed pathway significantly reversed inhibitor SRI-37330. Deficiency alleviates pathway-mediated pyroptosis, which might be novel therapeutic strategy for combating

Language: Английский

Citations

9
Mechanistic and therapeutic insights into the function of N6-methyladenosine in arthritic diseases DOI
Xinyue Zhou,

Yajie Wu,

Yingqiu Song

et al.

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: Jan. 7, 2025

Language: Английский

Citations

1
Mechanisms and clinical landscape of N6-methyladenosine (m6A) RNA modification in gastrointestinal tract cancers DOI Creative Commons

Danhua Zhu,

Kunkai Su, Xiaoxi Ouyang

et al.

Molecular and Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 479(7), P. 1553 - 1570

Published: June 10, 2024

Abstract Epigenetics encompasses reversible and heritable chemical modifications of non-nuclear DNA sequences, including RNA methylation, histone modifications, non-coding chromatin rearrangements. In addition to well-studied methylation has emerged as a hot topic in biological sciences over the past decade. N6-methyladenosine (m6A) is most common abundant modification eukaryotic mRNA, affecting all stages, transcription, translation, degradation. Advances high-throughput sequencing technologies made it feasible identify basis functions m6A RNA. Dysregulation levels associated modifying proteins can both inhibit promote cancer, highlighting importance tumor microenvironment diverse processes. Gastrointestinal tract cancers, gastric, colorectal, pancreatic are among deadly malignancies humans. Growing evidence suggests close association between progression gastrointestinal tumors. Global substantially modified tissues cell lines compared healthy cells, possibly influencing various behaviors such proliferation, invasion, metastasis, drug resistance. Exploring diagnostic therapeutic potential m6A-related critical from clinical standpoint. Developing more specific effective modulators offers new options for treating these tumors deeper insights into cancers.

Language: Английский

Citations

8
BCLAF1 drives esophageal squamous cell carcinoma progression through regulation of YTHDF2-dependent SIX1 mRNA degradation DOI
Peipei Zhang, Weiguang Zhang, Xiaoqing Wang

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 591, P. 216874 - 216874

Published: April 16, 2024

Language: Английский

Citations

7
Role of m6A RNA Methylation in Ischemic Stroke DOI
Yayun Xu, Wenqiang Liu, Lijie Ren

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(9), P. 6997 - 7008

Published: Feb. 16, 2024

Language: Английский

Citations

6
Reading the m6A-encoded epitranscriptomic information in development and diseases DOI Creative Commons

Yunbing Chen,

Ziyu Zhou, Yanxi Chen

et al.

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 28, 2024

Abstract N 6 -methyladenosine (m A) represents the most prevalent internal and reversible modification on RNAs. Different cell types display their unique m A profiles, which are determined by functions of writers erasers. M modifications lead to different outcomes such as decay, stabilization, or transport The A-encoded epigenetic information is interpreted readers interacting proteins. essential for biological processes, defects in have been discovered diverse diseases. Here, we review latest advances roles development These recent studies not only highlight importance regulating fate transitions, but also point potential application drugs targeting

Language: Английский

Citations

6
METTL3 promotes osteoblast ribosome biogenesis and alleviates periodontitis DOI Creative Commons
Yiwen Zhang,

Yiping Kong,

Wenjie Zhang

et al.

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 24, 2024

Abstract Background Periodontitis is a highly prevalent oral disease characterized by bacterium-induced periodontal inflammation and alveolar bone destruction. Osteoblast function impaired in periodontitis with global proteome change. METTL3 the pivotal methyltransferase of N 6 -methyladenosine (m A) that recently proved to exert crucial role osteoblast differentiation. This study aims investigate ribosome biogenesis progression. Results was knocked down osteoblasts, downregulated genes were enriched translation. knockdown inhibited oxidative phosphorylation LPS-stimulated whereas overexpression facilitated ribosomal mitochondrial function. Mechanistically, mediated biological behaviors activating Wnt/β-catenin/c-Myc signaling. depletion enhanced mRNA expression stability Dkk3 Sostdc1 via YTHDF2. In mice, inhibitor SAH promoted loss local inflammatory status, which partially rescued Wnt/β-catenin pathway activator CHIR-99021 HCl. Conclusions signaling LPS-treated osteoblasts alleviated destruction mice.

Language: Английский

Citations

5
m6A RNA Methylation and Implications for Hepatic Lipid Metabolism DOI
Xinyue Ming, Shirui Chen, Huijuan Li

et al.

DNA and Cell Biology, Journal Year: 2024, Volume and Issue: 43(6), P. 271 - 278

Published: April 18, 2024

This review presents a summary of recent progress in research on the N6-methyladenosine (m6A) modification and regulatory roles hepatic lipid metabolism. As most abundant internal eukaryotic RNA, m6A is dynamic reversible process enzyme system, which includes writers, erasers, readers. methylation depressed synthesis facilitated lipolysis liver. The depletion methyltransferase Mettl14/Mettl3 raised fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD1), acetyl-CoA carboxylase (ACC), elongase very long chain acids 6 (ELOVL6) rodent liver, causing increases liver weight, triglyceride (TG) production, content hepatocytes. FTO catalyzed demethylation suppression reader YTHDC2 promoted hepatocellular TG generation steatosis C57BL/6 mice through sterol element-binding protein 1c (SREBP-1c) signaling pathway, upregulated lipogenic genes

Language: Английский

Citations

4
The biological function of the N6-Methyladenosine reader YTHDC2 and its role in diseases DOI Creative Commons
Xudong Wu, Hui Chen, Kai Li

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 24, 2024

Abstract N6-methyladenosine (m6A) stands as the most prevalent modified form of RNA in eukaryotes, pivotal various biological processes such regulating stability, translation, and transcription. All members within YT521-B homology (YTH) gene family are categorized m6A reading proteins, capable identifying binding modifications on RNA, thereby metabolism functioning across diverse physiological processes. YTH domain-containing 2 (YTHDC2), identified latest member family, has only recently started to emerge for its function. Numerous studies have underscored significance YTHDC2 human physiology, highlighting involvement both tumor progression non-tumor diseases. Consequently, this review aims further elucidate pathological mechanisms by summarizing functions roles tumors other diseases, with a particular focus downstream molecular targets signaling pathways.

Language: Английский

Citations

4