TGM2 inhibits the proliferation, migration and tumorigenesis of MDCK cells

Qiu, Zhenyu; Guo, Shouqing; Li, Geng; Pei, Mengyuan; Liao, Yuejiao; Wang, Jiamin; Zhang, Jiayou; Yang, Di; Qiao, Zhihua; Li, Zhuo; Ma, Zufu; Liu, Zhenbin; Yang, Xiaoming

doi:10.1371/journal.pone.0285136

Cited by 3 publications

(4 citation statements)

References 46 publications

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“…Multiple genes were found to be strongly regulated during the tumorigenic transformation of MDCK cells. With the advent of the bioinformatics era, more molecules that are key to the tumorigenic transformation of MDCK cells have been identi ed, such as TGM2, which has been shown to function as an oncogene processes related to the tumorigenic phenotype of MDCK cells [7]. Subsequently, we found that the expression levels of CUL3 and EGFR were signi cantly upregulated in highly tumorigenic MDCK cells, and these two genes have been suggested to be important factors that in uence the tumorigenicity of MDCK cells [22].…”

Section: Discussionmentioning

confidence: 99%

“…When inoculated into nude mice (immunode cient animals), MDCK cells can cause subcutaneous tumorigenesis; however, the cell line exhibits signi cant heterogeneity, which has led to signi cant debate about its safety [6]. In uenza vaccines that are produced in tumorigenic cell lines may transfer oncogene-mediated neoplastic activity to vaccine recipients [7]. It has been demonstrated that nontumorigenic MDCK cells are a relatively safe substrate for vaccine production, and the risk to recipients of in uenza vaccines that are produced in nontumorigenic MDCK cells is minimal.…”

Section: Introductionmentioning

confidence: 99%

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MiR-2779-x, a Key microRNA that is Related to the Tumorigenicity of the MDCK Cell Line

Shi,

Yang,

Huang

et al. 2024

Preprint

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MDCK cells are the preferred cell line for influenza vaccine production, and the tumorigenicity of this cell line is a major concern with respect to its safety for vaccine production. However, the effect of miRNAs on the tumorigenicity of MDCK cells is poorly understood. In this study, we performed high-throughput sequencing of miRNAs in four MDCK cell lines with different degrees of tumorigenicity. Thereafter, the functions of these differentially expressed miRNAs were explored by miRNA target gene prediction, and we identified miR-2779-x as a key miRNA that is involved in the tumorigenicity of MDCK cells. Overexpression of miR-2779-x could decreased the tumorigenicity of MDCK cells in vivo and vitro. Dual luciferase binding reporter assay and Western blotting showed that miR-2779-x targeted and inhibited Bak1 protein expression. The effect of miR-2779-x on the tumorigenicity of MDCK cells in vitro was evaluated by Cell Counting Kit-8, wound healing and transwell invasion assays. Overexpression of miR-2779-x decreased cell proliferation and migration but increased cell invasion. In conclusion, we obtained evidence for the involvement of miRNAs in the tumorigenic phenotype of MDCK cells and provided novel insight into the establishment of MDCK cell lines that lack tumorigenicity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MiR-2779-x, a Key microRNA that is Related to the Tumorigenicity of the MDCK Cell Line

Shi,

Yang,

Huang

et al. 2024

Preprint

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“…Guo created a stable MDCK cell line with tissue transglutaminase 2 (TGM2) overexpression and knockdown and investigated the effect of TGM2 on influenza A (H1N1) virus growth in MDCK cells. The results showed that knocking down the TGM2 gene boosted the expression of the viral nucleoprotein (NP) gene and raised the virus titer considerably [31].…”

Section: Discussionmentioning

confidence: 99%

The Screening and Mechanism of Influenza-Virus Sensitive MDCK Cell Lines for Influenza Vaccine Production

Yang,

Yu,

et al. 2024

Diseases

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Influenza is a potentially fatal acute respiratory viral disease caused by the influenza virus. Influenza viruses vary in antigenicity and spread rapidly, resulting in seasonal epidemics. Vaccination is the most effective strategy for lowering the incidence and fatality rates of influenza-related disorders, and it is also an important method for reducing seasonal influenza infections. Mammalian Madin–Darby canine kidney (MDCK) cell lines are recommended for influenza virus growth, and such cell lines have been utilized in several commercial influenza vaccine productions. The limit dilution approach was used to screen ATCC-MDCK cell line subcellular strains that are especially sensitive to H1N1, H3N2, BV, and BY influenza viruses to increase virus production, and research on influenza virus culture media was performed to support influenza virus vaccine development. We also used RNA sequencing to identify differentially expressed genes and a GSEA analysis to determine the biological mechanisms underlying the various levels of susceptibility of cells to influenza viruses. MDCK cell subline 2B6 can be cultured to increase titer and the production of the H1N1, H3N2, BV, and BY influenza viruses. MDCK-2B6 has a significantly enriched and activated in ECM receptor interaction, JAK-STAT signaling, and cytokine receptor interaction signaling pathways, which may result in increased cellular susceptibility and cell proliferation activity to influenza viruses, promote viral adsorption and replication, and elevate viral production, ultimately. The study revealed that MDCK-2B6 can increase the influenza virus titer and yield in vaccine production by increasing cell sensitivity and enhancing proliferative activity.

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“…Among these, MDCK cells are recognized as the most advantageous cellular substrate due to their exceptional efficacy in infecting influenza viruses, rapid proliferation, and reduced susceptibility to mutation [ 8 , 9 ]. It is worth mentioning that the MDCK cell line represents a new cell substrate for a robust influenza vaccine production in a fully defined process [ 10 , 11 , 12 ].…”

Section: Introductionsmentioning

confidence: 99%

Enhanced Downstream Processing for a Cell-Based Avian Influenza (H5N1) Vaccine

Li,

Liu,

Xiong

et al. 2024

Vaccines

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H5N1 highly pathogenic avian influenza virus (HPAIV) infections pose a significant threat to human health, with a mortality rate of around 50%. Limited global approval of H5N1 HPAIV vaccines, excluding China, prompted the need to address safety concerns related to MDCK cell tumorigenicity. Our objective was to improve vaccine safety by minimizing residual DNA and host cell protein (HCP). We developed a downstream processing method for the cell-based H5N1 HPAIV vaccine, employing CaptoTM Core 700, a multimodal resin, for polishing. Hydrophobic-interaction chromatography (HIC) with polypropylene glycol as a functional group facilitated the reversible binding of virus particles for capture. Following the two-step chromatographic process, virus recovery reached 68.16%. Additionally, HCP and DNA levels were reduced to 2112.60 ng/mL and 6.4 ng/mL, respectively. Western blot, high–performance liquid chromatography (HPLC), and transmission electron microscopy (TEM) confirmed the presence of the required antigen with a spherical shape and appropriate particle size. Overall, our presented two-step downstream process demonstrates potential as an efficient and cost-effective platform technology for cell-based influenza (H5N1 HPAIV) vaccines.

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TGM2 inhibits the proliferation, migration and tumorigenesis of MDCK cells

Cited by 3 publications

References 46 publications

MiR-2779-x, a Key microRNA that is Related to the Tumorigenicity of the MDCK Cell Line

MiR-2779-x, a Key microRNA that is Related to the Tumorigenicity of the MDCK Cell Line

The Screening and Mechanism of Influenza-Virus Sensitive MDCK Cell Lines for Influenza Vaccine Production

Enhanced Downstream Processing for a Cell-Based Avian Influenza (H5N1) Vaccine

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