Fbxo6 confers drug‐sensitization to cisplatin <i>via</i> inhibiting the activation of Chk1 in non‐small cell lung cancer

Cai, Lin; Li, Jingduo; Zhao, Jing; Guo, Yingxue; Xie, Menghua; Zhang, Xiupeng; Wang, Liang; Tian, Hua; Li, Ailin; Li, Qingchang; Miao, Yuan

doi:10.1002/1873-3468.13461

Cited by 19 publications

(14 citation statements)

References 22 publications

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“…It seemed consistent with the role of FBXO2 as a tumor suppressor. It has been proved that low levels of FBXO6 and consequent impairment of replication stress-induced Chk1 degradation are associated with resistance to camptothecin of BC [13], the similar results about drug-resistance have been con rmed in small cell lung cancer by Cai et al [41]. We also found that up-regulated FBXO6 represented superior RFS in HER2 and TNBC types of patients.…”

Section: Discussionsupporting

confidence: 85%

Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer

Liu

Pan

et al. 2021

Preprint

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Background: Breast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated.Methods: In this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan-Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. We also showed that knockdown of FBXO1 in MCF7 and MDA-MB-231 cell lines resulted in decreased cell proliferation and migration in vitro. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan-Meier Plotter databases. Results: We found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, we identified that FBXO1 was an excellent molecular biomarker and therapeutic target for different molecular typing of BC. Conclusion: This study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with different molecular typing of BC. In addition, the overexpression of FBXO1 is always found in breast cancer and predicts disadvantageous prognosis, implicating it could as an appealing therapeutic target for breast cancer patients.

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Section: Discussionsupporting

confidence: 85%

Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer

Liu

Pan

et al. 2021

Preprint

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“…It seemed consistent with the role of FBXO2 as a tumor suppressor. It has been proved that low levels of FBXO6 and consequent impairment of replication stress-induced Chk1 degradation are associated with resistance to camptothecin of BC [13], the similar results about drugresistance have been con rmed in small cell lung cancer [14]. We also found that up-regulated FBXO6 represented superior RFS in HER2 and TNBC types of patients.…”

Section: Discussionsupporting

confidence: 76%

“…Zhang et al [13] have found that FBXO6 facilitates the ubiquitination and mediates the degradation of Chk1 to increase certain drugs resistance of tumor cells. However, in a recent research, Cai et al have proved that high levels of FBXO6 can decrease the expression and phosphorylation of Chk1, further inhibit the proliferation, facilitate the apoptosis and promote the cisplatin sensitivity of non-small cell lung cancer [14]. As the component of the SCF complex, FBXO16 interacts physically with the C-terminal domain of nuclear β-catenin protein to promote its lysine 48-linked polyubiquitination and mediate degradation of βcatenin [15].…”

Section: Introductionmentioning

confidence: 99%

Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer

Liu

Pan

et al. 2020

Preprint

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Background: Breast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated.Methods: In this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan-Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan-Meier Plotter databases.Results: We found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, we identified that FBXO1 was an excellent molecular biomarker and therapeutic target for BC. Conclusion: This study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with BC.

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“…F-box protein 6 (FBXO6) is a subunit of the ubiquitin protein ligase complex (70). Previous studies have demonstrated that FBXO6 inhibits tumor invasion in gastric and lung cancer; however, the underling mechanisms were not clear (71). In our co-expression analysis, we found that FBXO6 and ETVT were co-expressed with immunoproteasomes 20S, interferon-gamma regulator IRF-1, and protease activator PA28.…”

Section: Discussionmentioning

confidence: 69%

CD8+ T Cell Co-Expressed Genes Correlate With Clinical Phenotype and Microenvironments of Urothelial Cancer

et al. 2020

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PurposeTo identify immune-related co-expressed genes that promote CD8+ T cell infiltration in bladder cancer, and to explore the interactions among relevant genes in the tumor microenvironment.MethodWe obtained bladder cancer gene matrix and clinical information data from TCGA, GSE32894 and GSE48075. The “estimate” package was used to calculate tumor purity and immune score. The CIBERSORT algorithm was used to assess CD8+ T cell proportions. Weighted gene co-expression network analysis was used to identify the co-expression modules with CD8+ T cell proportions and bladder tumor purity. Subsequently, we performed correlation analysis among angiogenesis factors, angiogenesis inhibitors, immune inflammatory responses, and CD8+ T cell related genes in tumor microenvironment.ResultsA CD8+ T cell related co-expression network was identified. Eight co-expressed genes (PSMB8, PSMB9, PSMB10, PSME2, TAP1, IRF1, FBOX6, ETV7) were identified as CD8+ T cell-related genes that promoted infiltration of CD8+ T cells, and were enriched in the MHC class I tumor antigen presentation process. The proteins level encoded by these genes (PSMB10, PSMB9, PSMB8, TAP1, IRF1, and FBXO6) were lower in the high clinical grade patients, which suggested the clinical phenotype correlation both in mRNA and protein levels. These factors negatively correlated with angiogenesis factors and positively correlated with angiogenesis inhibitors. PD-1 and PD-L1 positively correlated with these genes which suggested PD-1 expression level positively correlated with the biological process composed by these co-expression genes. In the high expression group of these genes, inflammation and immune response were more intense, and the tumor purity was lower, suggesting that these genes were immune protective factors that improved the prognosis in patients with bladder cancer.ConclusionThese co-expressed genes promote high levels of infiltration of CD8+ T cells in an immunoproteasome process involved in MHC class I molecules. The mechanism might provide new pathways for treatment of patients who are insensitive to PD-1 immunotherapy due to low degrees of CD8+ T cell infiltration.

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Fbxo6 confers drug‐sensitization to cisplatin via inhibiting the activation of Chk1 in non‐small cell lung cancer

Cited by 19 publications

References 22 publications

Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer

Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer

Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer

CD8+ T Cell Co-Expressed Genes Correlate With Clinical Phenotype and Microenvironments of Urothelial Cancer

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