Fbxo45 facilitates pancreatic carcinoma progression by targeting USP49 for ubiquitination and degradation

Wu, Linhui; Yu, Ke; Chen, Kai; Zhu, Xingyi; Zheng, Yufeng; Wang, Qi; Gao, Junjie; Wang, Yingying; Cao, Tong; Xu, Hui; Pan, Xueshan; Wang, Lixia; Xia, Jun; Li, Yuyun; Wang, Zhi-wei; Ma, Jia

doi:10.1038/s41419-022-04675-2

Cited by 30 publications

(19 citation statements)

References 38 publications

(55 reference statements)

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“…The membrane was incubated with 5% non-fat milk and then incubated with METTL3 (1:1000), PD-L1 (1:1,000) or Tubulin (1:1,000) antibody for overnight at 4°C. The membranes were washed by TBST and then incubated with the secondary antibody for 1 h. Then, ECL method was used to examine the protein expression ( 33 ).…”

Section: Methodsmentioning

confidence: 99%

LncRNA MALAT1 regulates METTL3-mediated PD-L1 expression and immune infiltrates in pancreatic cancer

et al. 2022

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Pancreatic cancer is the fourth leading cause of cancer death in the United States. The main methods of treating pancreatic cancer are surgery and chemotherapy, but the treatment efficacy is low with a poor prognosis. Immunotherapy represented by PD-1/PD-L1 has brought a milestone progress in the treatment of pancreatic cancer. However, the unique tumor microenvironment of pancreatic cancer presents challenges for immunotherapy. In addition, m6A is a common RNA modification and a potential molecular target in tumor therapy. The expression pattern of m6A in pancreatic cancer is still unclear. LncRNAs also play an essential role in pancreatic cancer development and treatment. In this study, we found that some m6A regulators were significantly elevated in pancreatic cancer and associated with the expression of PD-1/PD-L1. Moreover, we observed that METTL3 can increase the expression of PD-L1. Notably, METTL3 positively regulates the expression of lncRNA MALAT1 in pancreatic cancer cells. Strikingly, lncRNA MALAT1 increased the expression of PD-L1 in pancreatic cancer cells. This finding indicated that METTL3 regulated the expression of PD-L1 possibly via targeting lncRNA MALAT1 in pancreatic cancer cells. Lastly, MALAT1 governed the viability of pancreatic cancer cells. Taken together, lncRNA MALAT1 is involved in METTL3-mediated promotion of PD-L1 expression in pancreatic cancer.

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Section: Methodsmentioning

confidence: 99%

LncRNA MALAT1 regulates METTL3-mediated PD-L1 expression and immune infiltrates in pancreatic cancer

et al. 2022

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“…Specific small hairpin RNAs (shRNAs) targeting METTL3 (shMETTL3) and the control shRNA (shNC) were obtained (GenePharma, Shanghai, China). Lipofectamine 2000 was used for transfection as described before ( 20 ).…”

Section: Methodsmentioning

confidence: 99%

Expression profiles of m6A RNA methylation regulators, PD-L1 and immune infiltrates in gastric cancer

Chen¹,

Shu²,

Zhang

et al. 2022

Front. Oncol.

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Gastric cancer is the fourth most frequent cancer and has a high death rate. Immunotherapy represented by PD-1 has brought hope for the treatment of advanced gastric cancer. Methylation of the m6A genes is linked to the onset and progression of numerous cancers, but there are few studies on gastric cancer. The main purpose of this study aims to analyze the relationship between m6A RNA methylation regulators, PD-L1, prognosis and tumor immune microenvironment (TIME) in gastric cancer. The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases were used to acquire transcriptomic data and clinical information from gastric cancer patients. The changes in m6A regulator expression levels in gastric cancer tissues and normal tissues were studied. Consensus clustering analysis was used to separate gastric cancer samples into two categories. We employed Least Absolute Shrinkage, Selection Operator (LASSO) Cox regression analysis, Gene Set Enrichment Analysis (GSEA), and cBioPortal to analyze the m6A regulators, PD-L1 and TIME in gastric cancer. In gastric cancer tissues, the majority of m6A regulatory factors are considerably overexpressed. Two gastric cancer subgroups (Cluster1/2) based on consensus clustering of 21 m6A regulators. PD-L1 and PD-1 expression levels were significantly higher in gastric cancer tissues, and they were significantly linked with METTL3, WTAP, HNRNPD, ZC3H7B, METTL14, FTO, PCIF1, HNRNPC, YTHDF1 and YTDHF2. Cluster1 showed a large increase in resting memory CD4+ T cells, regulatory T cells, naïve B cells, active NK cells, and resting Mast cells. Cluster1 and Cluster2 were shown to be involved in numerous critical signaling pathways, including base excision repair, cell cycle, nucleotide excision repair, RNA degradation, and spliceosome pathways. Gastric cancer RiskScores based on prognostic factors have been found as independent prognostic indicators. The amount of tumor-infiltrating immune cells is dynamically affected by changes in the copy number of m6A methylation regulators associated with TIME.

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“…Clinically, decreased USP49 expression in patients with pancreatic cancer is associated with decreased FKBP51 expression and increased phosphorylation of AKT [ 154 ]. Recently, a conserved F-box protein, Fbxo45, was shown to interact with USP49 in pancreatic cancer cells, resulting in increased cell viability and motility capacity [ 155 ].…”

Section: Pancreatic Cancermentioning

confidence: 99%

Deubiquitinases in Cancers: Aspects of Proliferation, Metastasis, and Apoptosis

Liu

LEUNG

Liang

et al. 2022

Cancers

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Deubiquitinases (DUBs) deconjugate ubiquitin (UBQ) from ubiquitylated substrates to regulate its activity and stability. They are involved in several cellular functions. In addition to the general biological regulation of normal cells, studies have demonstrated their critical roles in various cancers. In this review, we evaluated and grouped the biological roles of DUBs, including proliferation, metastasis, and apoptosis, in the most common cancers in the world (liver, breast, prostate, colorectal, pancreatic, and lung cancers). The current findings in these cancers are summarized, and the relevant mechanisms and relationship between DUBs and cancers are discussed. In addition to highlighting the importance of DUBs in cancer biology, this study also provides updated information on the roles of DUBs in different types of cancers.

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Fbxo45 facilitates pancreatic carcinoma progression by targeting USP49 for ubiquitination and degradation

Cited by 30 publications

References 38 publications

LncRNA MALAT1 regulates METTL3-mediated PD-L1 expression and immune infiltrates in pancreatic cancer

LncRNA MALAT1 regulates METTL3-mediated PD-L1 expression and immune infiltrates in pancreatic cancer

Expression profiles of m6A RNA methylation regulators, PD-L1 and immune infiltrates in gastric cancer

Deubiquitinases in Cancers: Aspects of Proliferation, Metastasis, and Apoptosis

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