Study of single nucleotide polymorphisms of <i>FBW7</i> and its substrate genes revealed a predictive factor for paclitaxel plus cisplatin chemotherapy in Chinese patients with advanced esophageal squamous cell carcinoma

Liu, Ying; Xu, Shu; Chen, Yong Shun; Wu, Xudong; Qiao, Li; Li, Ke; Yuan, Long

doi:10.18632/oncotarget.9736

Cited by 2 publications

(3 citation statements)

References 35 publications

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“…Other authors have shown that mTOR can be used as a substrate protein of FBW7 and can be modified by ubiquitination and degraded by proteasomes [9]. Our study confirmed that FBW7 plays a role similar to rapamycin to enhance the autophagy level by degradation of mTOR.…”

Section: Discussionsupporting

confidence: 87%

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FBW7 Regulates the Autophagy Signal in Mesangial Cells Induced by High Glucose

Gao

Fan

Chen

et al. 2019

BioMed Research International

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Aims. Abnormal regulation of autophagy participates in the development of diabetic nephropathy. mTOR is the most common negative regulator of the autophagy signaling pathway. FBW7 constitutes the SCF (Skp1–Cullin1–F-box protein) recognition subunit of E3 ubiquitin ligase, and mTOR is a substrate of FBW7 that can be modified by ubiquitination and be degraded via proteasomes. In this study, we explored the relationship between FBW7 and autophagy and examined the effects of FBW7 on the occurrence of diabetic nephropathy in vitro. Materials and Methods. We cultured mesangial cells induced by high glucose in vitro and used rapamycin as a specific mTOR inhibitor, performed FBW7 gene overexpression, and detected the expression of autophagy signal and inflammatory factors by WB, ELISA, RT-PCR, and immunofluorescence. Results. High glucose can downregulate the expression of FBW7 and activate mTOR signal, which leads to diminished autophagy in renal mesangial cells, as well as renal inflammatory cytokines and fibrotic factors. RAPA, as a specifically inhibitor of mTOR, can decrease inflammatory cytokines and fibrotic factors by inhibiting mTOR. Moreover, FBW7 gene overexpression can increase autophagy by inhibiting mTOR signal; at the same time, the inflammatory cytokines and fibrotic factors were decreased in mesangial cells. Conclusions. FBW7 was decreased in renal mesangial cells induced by high glucose, and FBW7 gene overexpression can increase autophagy by inhibiting mTOR signaling and ameliorate inflammation and fibrosis.

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Section: Discussionsupporting

confidence: 87%

“…Moreover, the level of autophagy was lower in DN mouse than in normal mice [8]. P13K-Akt-mTOR constitutes the most common negative-regulatory signaling pathway of the cell; mTOR, the substrate of FBW7, can be modified by ubiquitination and degraded by proteasomes [9].…”

Section: Introductionmentioning

confidence: 99%

FBW7 Regulates the Autophagy Signal in Mesangial Cells Induced by High Glucose

Gao

Fan

Chen

et al. 2019

BioMed Research International

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“…For example, one study identified that SNPs of interferon regulatory factor-4 (IRF4) were associated with melanoma development [ 13 ]. Another study validated that SNPs of F-box and WD repeat domain containing 7 (FBW7) could be the predictive factor for paclitaxel plus cisplatin chemotherapy in patients with advanced esophageal squamous cell carcinoma [ 14 ]. Moreover, SNP of WWOX was found to represent a major predictive factor in gemcitabine-treated pancreatic cancer [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms of Wnt/β-catenin pathway genes are associated with the efficacy and toxicities of radiotherapy in patients with nasopharyngeal carcinoma

Huang

Liu

et al. 2016

Oncotarget

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Radiotherapy (RT) is the normative therapeutic treatment for primary nasopharyngeal carcinoma (NPC). Single nucleotide polymorphisms (SNPs) of genes in Wnt/β-catenin pathway are correlated to the development, prognosis, and treatment benefit of various cancers. However, it has not been established whether SNPs of Wnt/β-catenin pathway are associated with nasopharyngeal tumorigenesis and the efficacy of RT in NPC patients. Therefore, in this study, we aimed to investigate the nine potentially functional SNPs of four genes in the Wnt/β-catenin pathway and genotyped these in 188 NPC patients treated with RT. To achieve this goal, associations between these SNPs and the RT's curative efficacy, as well as acute radiation-induced toxic reaction were determined by multifactorial logistic regression. We observed that catenin beta 1 gene (CTNNB1) rs1880481 and rs3864004, and glycogen synthase kinase 3 beta gene (GSK3β) rs3755557 polymorphisms were significantly associated with poorer efficacy of RT in NPC patients. Moreover, GSK3β rs375557 and adenomatous polyposis coli gene (APC) rs454886 polymorphisms were correlated with acute grade 3–4 radiation-induced dermatitis and oral mucositis, respectively. In conclusion, this study suggests that gene polymorphisms of Wnt/β-catenin may be novel prognostic factors for NPC patients treated with RT.

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Study of single nucleotide polymorphisms of FBW7 and its substrate genes revealed a predictive factor for paclitaxel plus cisplatin chemotherapy in Chinese patients with advanced esophageal squamous cell carcinoma

Cited by 2 publications

References 35 publications

FBW7 Regulates the Autophagy Signal in Mesangial Cells Induced by High Glucose

FBW7 Regulates the Autophagy Signal in Mesangial Cells Induced by High Glucose

Genetic polymorphisms of Wnt/β-catenin pathway genes are associated with the efficacy and toxicities of radiotherapy in patients with nasopharyngeal carcinoma

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