Drug repositioning in head and neck squamous cell carcinoma: An integrated pathway analysis based on connectivity map and differential gene expression

Wei, Gan-Guan; Li, Gao; Tang, Zhengyi; Lin, Peng; Liang, Li; Zeng, Jingjing; Chen, Gang; Chen, Gang

doi:10.1016/j.prp.2019.03.007

Cited by 16 publications

(11 citation statements)

References 66 publications

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“…As one of the most common cancer around the world, HNSCC is a debilitating cancer with unfavorable patient outcomes and survival rates [2, 3]. In addition, HNSCC exerts a massive burden on the patients’ health and society [4]. Currently, palliative-intent therapy is regarded as a systemic treatment for patients suffering from recurrent and metastatic HNSCC [5].…”

Section: Introductionmentioning

confidence: 99%

The let-7 family of microRNAs suppresses immune evasion in head and neck squamous cell carcinoma by promoting PD-L1 degradation

Liu

Han

et al. 2019

Cell Commun Signal

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Background: Accumulation of immunosuppressive protein programmed death-ligand 1 (PD-L1) has been documented in several cancers and contributes to the evasion of the host immune system. However, cancer cellintrinsic signaling-dependent control of PD-L1 expression remains to be elucidated. Herein, we aimed to identify the let-7 family of microRNAs as candidates that up-regulate tumor cell PD-L1 expression and mediates immune evasion of head and neck squamous cell carcinoma (HNSCC). Methods: The expression of let-7 family and PD-L1 was quantified in HNSCC tissues and adjacent normal tissues. PD-L1 degradation was evaluated in HNSCC cells in response to elevated expressions of let-7a or let-7b. The regulation of let-7 family on PD-L1 degradation through a mechanism involving T-cell factor-4 (TCF-4) control of βcatenin/STT3 pathway was evaluated. Immune recognition of HNSCC in vivo was examined in subcutaneous tumorbearing C3H mice in the presence of let-7a/b and/or CTLA-4 antibody. Results: The let-7 family were significantly down-regulated in the context of HNSCC, sharing a negative correlation with PD-L1 expression. Glycosylated PD-L1 was detected in HNSCC cells, which was reduced by let-7a/b overexpression. TCF-4, the target of let-7a/b, activated the β-catenin/STT3 pathway and promoted PD-L1 degradation. In vivo analysis demonstrated that let-7a/b over-expression potentiated anticancer immunotherapy by CTLA-4 blockade. Conclusions: Taken together, our findings highlight targeting let-7 family as a potential strategy to enhance immune checkpoint therapy for HNSCC.

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Section: Introductionmentioning

confidence: 99%

The let-7 family of microRNAs suppresses immune evasion in head and neck squamous cell carcinoma by promoting PD-L1 degradation

Liu

Han

et al. 2019

Cell Commun Signal

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“…1-Naphthyl, a derivative of quipazine, can exert a tumor suppressive effect by inducing oxidative stress in melanoma cells [70]. MG-262, a proteasome inhibitor, which was reported by Wei et al through CMap analysis and found that MG-262 may be a targeted therapeutic drug for head and neck squamous cell carcinoma [71]. Transcription replication will become an effective target of the proteasome inhibitor MG-262 in cancer chemotherapy, which can enhance the sensitivity of cancer cells to cisplatin, but has little effect on normal cells [72].…”

Section: Discussionmentioning

confidence: 95%

Identification of a novel small nucleolar RNAs prognostic signature for patients with acute myelocytic leukemia

Huang¹,

Liao²,

Li³

2020

Preprint

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Background: This study mainly used The Cancer Genome Atlas (TCGA) RNA sequencing dataset to screen prognostic snoRNAs of acute myeloid leukemia (AML), and used for the construction of prognostic snoRNAs signature for AML. Methods: A total of 130 AML patients with RNA sequencing dataset were used for prognostic snoRNAs screenning. SnoRNAs co-expressed genes and differentially expressed genes (DEGs) were used for functional annotation, as well as gene set enrichment analysis (GSEA). Connectivity Map (CMap) also used for potential targeted drugs screening. Results:Through genome-wide screening, we identified 30 snoRNAs that were significantly associated with the prognosis of AML. Then we used the step function to screen a prognostic signature composed of 14 snoRNAs (SNORD72, SNORD38, U3, SNORA73B, SNORD79, SNORA73, SNORD12B, SNORA74, SNORD116-12, SNORA65, SNORA14, snoU13, SNORA75, SNORA31), which can significantly divide AML patients into high- and low-risk groups. Through GSEA, snoRNAs co-expressed genes and DEGs functional enrichment analysis, we screened a large number of potential functional mechanisms of this prognostic signature in AML, such as phosphatidylinositol 3-kinase-Akt ,Wnt, epithelial to mesenchymal transition, T cell receptors, NF-kappa B, mTOR and other classic cancer-related signaling pathways. In the subsequent targeted drug screening using CMap, we also identified six drugs that can be used for AML targeted therapy, they were alimemazine, MG-262, fluoxetine, quipazine, naltrexone and oxybenzone. Conclusion: Our current study was constructed an AML prognostic signature based on the 14 prognostic snoRNAs, which may serve as a novel prognostic biomarker for AML.

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“…Shi et al also identified 15-delta Prostaglandin J2 as a potential therapeutic agent by comparing gene expression profiles in patients with diabetic nephropathy using bioinformatics analysis (31). Wei et al through genome-wide data and CMAP analysis identified MC-262 as a potential targeted therapy for head and neck squamous cell carcinoma (HNSCC), and its potential target in HNSCC is proliferating cell nuclear antigen (32). Vorinostat in the treatment of glioma has been widely reported in previous studies.…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis of a Novel Eleven-Small Nucleolar RNA Prognostic Signature in Patients With Lower Grade Glioma

et al. 2021

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ObjectiveThe present study used the RNA sequencing (RNA-seq) dataset to identify prognostic snoRNAs and construct a prognostic signature of The Cancer Genome Atla (TCGA) lower grade glioma (LGG) cohort, and comprehensive analysis of this signature.MethodsRNA-seq dataset of 488 patients from TCGA LGG cohort were included in this study. Comprehensive analysis including function enrichment, gene set enrichment analysis (GSEA), immune infiltration, cancer immune microenvironment, and connectivity map (CMap) were used to evaluate the snoRNAs prognostic signature.ResultsWe identified 21 LGG prognostic snoRNAs and constructed a novel eleven-snoRNA prognostic signature for LGG patients. Survival analysis suggests that this signature is an independent prognostic risk factor for LGG, and the prognosis of LGG patients with a high-risk phenotype is poor (adjusted P = 0.003, adjusted hazard ratio = 2.076, 95% confidence interval = 1.290–3.340). GSEA and functional enrichment analysis suggest that this signature may be involved in the following biological processes and signaling pathways: such as cell cycle, Wnt, mitogen-activated protein kinase, janus kinase/signal transducer and activator of tran-ions, T cell receptor, nuclear factor-kappa B signaling pathway. CMap analysis screened out ten targeted therapy drugs for this signature: 15-delta prostaglandin J2, MG-262, vorinostat, 5155877, puromycin, anisomycin, withaferin A, ciclopirox, chloropyrazine and megestrol. We also found that high- and low-risk score phenotypes of LGG patients have significant differences in immune infiltration and cancer immune microenvironment.ConclusionsThe present study identified a novel eleven-snoRNA prognostic signature of LGG and performed a integrative analysis of its molecular mechanisms and relationship with tumor immunity.

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Drug repositioning in head and neck squamous cell carcinoma: An integrated pathway analysis based on connectivity map and differential gene expression

Cited by 16 publications

References 66 publications

The let-7 family of microRNAs suppresses immune evasion in head and neck squamous cell carcinoma by promoting PD-L1 degradation

The let-7 family of microRNAs suppresses immune evasion in head and neck squamous cell carcinoma by promoting PD-L1 degradation

Identification of a novel small nucleolar RNAs prognostic signature for patients with acute myelocytic leukemia

Integrative Analysis of a Novel Eleven-Small Nucleolar RNA Prognostic Signature in Patients With Lower Grade Glioma

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