Head and neck squamous cell carcinoma(HNSCC)still lacks effective targeted treatment.Therefore,exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC.Here,we reported that...Head and neck squamous cell carcinoma(HNSCC)still lacks effective targeted treatment.Therefore,exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC.Here,we reported that the expression levels of family with sequence similarity 64,member A(FAM64A)were significantly higher in HNSCC tissues and cell lines.In addition,FAM64A overexpression was found to be strongly associated with an unfavorable prognosis of HNSCC.Both in vitro and in vivo evidence showed that FAM64A depletion suppressed the malignant activities of HNSCC cells,and vice versa.Moreover,we found that the FAM64A level was progressively increased from normal to dysplastic to cancerous tissues in a carcinogenic 4-nitroquinoline-1-oxide mouse model.Mechanistically,a physical interaction was found between FAM64A and forkhead box protein M1(FOXM1)in HNSCC cells.FAM64A promoted HNSCC tumorigenesis not only by enhancing the transcriptional activity of FOXM1,but also,more importantly,by modulating FOXM1 expression via the autoregulation loop.Furthermore,a positive correlation between FAM64A and FOXM1 was found in multiple independent cohorts.Taken together,our findings reveal a previously unknown mechanism behind the activation of FOXM1 in HNSCC,and FAM64A might be a promising molecular therapeutic target for treating HNSCC.展开更多
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer mortality in the world and the 5th most commonly occurring cancer (Siegel, R. 2014). In the last few decades a growing interest fo...Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer mortality in the world and the 5th most commonly occurring cancer (Siegel, R. 2014). In the last few decades a growing interest for the emerging data from both tumor biology and multimodality treatment in HNSCC has been developed. A huge number of new markers need to be managed with bio-informatics systems to elaborate and correlate clinical and molecular data. Data mining algorithms are a promising medical application. We used this technology to correlate blood samples with clinical outcome in 120 patients treated with chemoradiation for locally advanced HNSCC. Our results did not find a significant correlation because of the sample exiguity but they show the potential of this tool.展开更多
The recurrence of head and neck squamous cell carcinoma(HNSCC)after surgical resection continues to pose a major challenge to cancer treatment.Advanced HNSCC exhibits a low response rate to immune checkpoint blockade(...The recurrence of head and neck squamous cell carcinoma(HNSCC)after surgical resection continues to pose a major challenge to cancer treatment.Advanced HNSCC exhibits a low response rate to immune checkpoint blockade(ICB),while photothermal therapy(PTT)can increase the infiltration of immune cells to make tumors more susceptible to cancer immunotherapy.In this regard,we designed and constructed a novel multifunctional nanocomposite comprised of oxidized bacterial cellulose(OBC),thrombin(TB),and gold nanocages(AuNCs)containing anti-programmed death 1(PD-1)antibody(αPD-1@AuNCs),which allows the combination of therapies with remarkable postoperative antitumor immunity to control local tumor recurrence.TheαPD-1@AuNCs displayed high light-to-heat conversion efficiency and induced pyroptosis under near infrared(NIR)irradiation,which activated a potent antitumor immune response.More importantly,the therapeutic system could induce tumor pyroptosis and enhance antitumor immune response by increasing T-cell infiltration and reducing the immune suppressive cells,when combined with local ICB therapy,which effectively avoided the tumor recurrence in a HNSCC postoperative mice model.Overall,the newly developed multifunctional nanocomposites could be a promising candidate for the treatment of postoperative HNSCC.展开更多
Background:Traditional Chinese medicine is promising for managing challenging and complex disorders,including cancer,and in particular,saffron is applied in treating various cancer types.However,its potential therapeu...Background:Traditional Chinese medicine is promising for managing challenging and complex disorders,including cancer,and in particular,saffron is applied in treating various cancer types.However,its potential therapeutic efficacy and active components in managing squamous cell carcinoma of the head and neck(HNSCC)remain unclear yet.Methods:Using network pharmacology approaches,active ingredients of saffron,their target genes,and HNSCC-related genes were identified.Enrichment analyses were conducted for determining molecular functions and pathways enriched by genes that overlapped between the saffron target gene set and the HNSCC gene set.Among the four known active ingredients of saffron,crocetin was found to have the strongest inhibitory impact on HNSCC,based on the findings of cell viability and migration assays.Therefore,the potential target genes of crocetin in HNSCC cells were examined using molecular docking experiments and were confirmed by qPCR.Result s:Four active ingredients of saffron and 184 of their target genes were identified.Further,a total of 34 overlapping saffron-/HNSCC-associated targets related to the four active ingredients were screened,and crocetin was chosen for further investigation because it had the strongest inhibitory effect on HNSCC cells.Molecular docking experiments indicated that ESR1 and CCND1 were the target genes of crocetin.These results were confirmed through qPCR analysis,in which crocetin was found to lower the expression of the ESR1 and CCND1 genes in AMC-HN-8 and FaDu cells.Conclusion:According to our results,crocetin is a primary active anti-cancer component of saffron that may have potential in the development of novel HNSCC-treating medications.However,more thorough molecular research is necessary for confirming these results and elucidating the anti-cancer mechanism underlying saffron.展开更多
Head and neck squamous cell carcinoma(HNSCC) is one of the most common human cancers;however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map(cMap) bas...Head and neck squamous cell carcinoma(HNSCC) is one of the most common human cancers;however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map(cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of parbendazole, and the direct binding between them was further verified. Parbendazole was further proved as an effective tubulin polymerization inhibitor, which can block the cell cycle, cause apoptosis and prevent cell migration, and it exhibited reasonable therapeutic effect and low toxicity in the in vivo and in vitro anti-tumor evaluation. Our study repositioned an anthelmintic parbendazole to treat HNSCC, which revealed a therapeutic utility and provided a new treatment option for human cancers.展开更多
Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevan...Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in HPSCC.Methods:In a preceding investigation,HSP90AA1,a differential gene,was discovered through transcriptome sequencing of HPSCC tissues,considering both the presence and absence of LM.Validation of HSP90AA1 expression was accomplished via qRT-PCR,western-blotting(WB),and immunohistochemistry(IHC),while its prognostic significance was assessed employing Kaplan–Meier survival analysis(KMSA),log-rank test(LR),and Cox’s regression analysis(CRA).Bioinformatics techniques facilitated the prediction and analysis of its plausible mechanisms in LM,further substantiated by in vitro and in vivo experiments utilizing FaDu cell lines.Results:HSP90AA1 is substantially upregulated in HPSCC with LM and is identified as an independent prognostic risk determinant.The down-regulation of HSP90AA1 can achieve inhibition of tumor cell proliferation,migration and invasion.Both in vivo experiments and Bioinformatics exploration hint at promoting LM by Epithelial-mesenchymal transition(EMT),regulated by HSP90AA1.Conclusions:HSP90AA1,by controlling EMT,can foster LM in HPSCC.This finding sets the foundation for delving into new therapeutic targets for HPSCC.展开更多
Aging is highly associated with tumor formation and progression.However,little research has explored the association of aging-related lncRNAs(ARLs)with the prognosis and tumor immune microenvironment(TIME)of head and ...Aging is highly associated with tumor formation and progression.However,little research has explored the association of aging-related lncRNAs(ARLs)with the prognosis and tumor immune microenvironment(TIME)of head and neck squamous cell carcinoma(HNSCC).RNA sequences and clinicopathological data of HNSCC patients and normal subjects were downloaded from The Cancer Genome Atlas.In the training group,we used Pearson correlation,univariate Cox regression,least absolute shrinkage/selection operator regression analyses,and multivariate Cox regression to build a prognostic model.In the test group,we evaluated the model.Multivariate Cox regression was done to screen out independent prognostic factors,with which we constructed a nomogram.Afterward,we demonstrated the predictive value of the risk scores based on the model and the nomogram using time-dependent receiver operating characteristics.Gene set enrichment analysis,immune correlation analysis,and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.The most important LINC00861 in the model was examined in HNE1,CNE1,and CNE2 nasopharyngeal carcinoma cell lines and transfected into the cell lines CNE1 and CNE2 using the LINC00861-pcDNA3.1 construct plasmid.In addition,CCK-8,Edu,and SA-β-gal staining assays were conducted to test the biofunction of LINC00861 in the CNE1 and CNE2 cells.The signature based on nine ARLs has a good predictive value in survival time,immune infiltration,immune checkpoint expression,and sensitivity to multiple drugs.LINC00861 expression in CNE2 was significantly lower than in the HNE1 and CNE1 cells,and LINC00861 overexpression significantly inhibited the proliferation and increased the senescence of nasopharyngeal carcinoma cell lines.This work built and verified a new prognostic model for HNSCC based on ARLs and mapped the immune landscape in HNSCC.LINC00861 is a protective factor for the development of HNSCC.展开更多
目的:探究头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中磷酸化Zeste同源增强子(enhancer of Zeste homolog 2,EZH2)的表达特征及对化疗敏感性的影响。方法:选取2018年1月至2021年3月天津医科大学肿瘤医院HNSCC患...目的:探究头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中磷酸化Zeste同源增强子(enhancer of Zeste homolog 2,EZH2)的表达特征及对化疗敏感性的影响。方法:选取2018年1月至2021年3月天津医科大学肿瘤医院HNSCC患者组织标本及临床资料53例。免疫组织化学染色分析HNSCC组织标本中p-EZH2^(S21)、p-STAT3^(Y705)、HIF-1α和Ki-67的表达水平。Western blot检测HNSCC组织和细胞株中p-EZH2^(S21)的表达情况。在HNSCC细胞中构建EZH2野生型(EZH2-WT)和EZH2^(S21)位点突变(EZH2-^(S21)A)的稳转细胞,CCK8实验和平板克隆实验检测EZH2以及^(S21)位点磷酸化对HNSCC细胞增殖能力及其对顺铂(cisplatin,DDP)和5-氟尿嘧啶(5-fluorouracil,5-FU)敏感性的影响。结果:HNSCC中p-EZH2^(S21)表达升高,并且与p-STAT3^(Y705)(P<0.05),HIF-1α(P<0.01)表达呈正相关。临床特征相关性分析发现HNSCC中p-EZH2^(S21)表达与淋巴结转移(P<0.0005)、T分期(P<0.05)、N分期(P<0.0001)和AJCC分期(P<0.05)呈正相关。体外实验证实EZH2表达促进HNSCC细胞增殖能力并且抑制其对化疗的敏感性,抑制EZH2^(S21)磷酸化可以恢复肿瘤细胞对DDP和5-FU的敏感性。结论:p-EZH2^(S21)在HNSCC肿瘤进展中具有重要作用,^(S21)位点磷酸化是EZH2影响HNSCC细胞增殖及其对化疗敏感性的重要途径。展开更多
基金supported by National Natural Science Foundation of China(81901006)Guangdong Basic and Applied Basic Research Foundation(2020A1515110051)+1 种基金Scientific Research Talent Cultivation Project of Stomatological Hospital,Southern Medical University(RC202005)Science Research Cultivation Program of Stomatological Hospital,Southern Medical University(PY2020002)。
文摘Head and neck squamous cell carcinoma(HNSCC)still lacks effective targeted treatment.Therefore,exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC.Here,we reported that the expression levels of family with sequence similarity 64,member A(FAM64A)were significantly higher in HNSCC tissues and cell lines.In addition,FAM64A overexpression was found to be strongly associated with an unfavorable prognosis of HNSCC.Both in vitro and in vivo evidence showed that FAM64A depletion suppressed the malignant activities of HNSCC cells,and vice versa.Moreover,we found that the FAM64A level was progressively increased from normal to dysplastic to cancerous tissues in a carcinogenic 4-nitroquinoline-1-oxide mouse model.Mechanistically,a physical interaction was found between FAM64A and forkhead box protein M1(FOXM1)in HNSCC cells.FAM64A promoted HNSCC tumorigenesis not only by enhancing the transcriptional activity of FOXM1,but also,more importantly,by modulating FOXM1 expression via the autoregulation loop.Furthermore,a positive correlation between FAM64A and FOXM1 was found in multiple independent cohorts.Taken together,our findings reveal a previously unknown mechanism behind the activation of FOXM1 in HNSCC,and FAM64A might be a promising molecular therapeutic target for treating HNSCC.
文摘Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer mortality in the world and the 5th most commonly occurring cancer (Siegel, R. 2014). In the last few decades a growing interest for the emerging data from both tumor biology and multimodality treatment in HNSCC has been developed. A huge number of new markers need to be managed with bio-informatics systems to elaborate and correlate clinical and molecular data. Data mining algorithms are a promising medical application. We used this technology to correlate blood samples with clinical outcome in 120 patients treated with chemoradiation for locally advanced HNSCC. Our results did not find a significant correlation because of the sample exiguity but they show the potential of this tool.
基金This work was supported by the National Natural Science Foundation of China(Nos.82072996(Z.J.S.)81874131(Z.J.S.)+1 种基金81702730(L.L.B.),and 51973076(G.Y.))the Fundamental Research Funds for the Central Universities(No.2042021kf0216)to Z.J.S.,China Postdoctoral Science Foundation(Nos.2018M630883 and 2019T120688)to L.L.B.,and Wuhan Young Medical Talents Training Project to L.L.B.
文摘The recurrence of head and neck squamous cell carcinoma(HNSCC)after surgical resection continues to pose a major challenge to cancer treatment.Advanced HNSCC exhibits a low response rate to immune checkpoint blockade(ICB),while photothermal therapy(PTT)can increase the infiltration of immune cells to make tumors more susceptible to cancer immunotherapy.In this regard,we designed and constructed a novel multifunctional nanocomposite comprised of oxidized bacterial cellulose(OBC),thrombin(TB),and gold nanocages(AuNCs)containing anti-programmed death 1(PD-1)antibody(αPD-1@AuNCs),which allows the combination of therapies with remarkable postoperative antitumor immunity to control local tumor recurrence.TheαPD-1@AuNCs displayed high light-to-heat conversion efficiency and induced pyroptosis under near infrared(NIR)irradiation,which activated a potent antitumor immune response.More importantly,the therapeutic system could induce tumor pyroptosis and enhance antitumor immune response by increasing T-cell infiltration and reducing the immune suppressive cells,when combined with local ICB therapy,which effectively avoided the tumor recurrence in a HNSCC postoperative mice model.Overall,the newly developed multifunctional nanocomposites could be a promising candidate for the treatment of postoperative HNSCC.
基金the Taishan Scholar Project(No.ts20190991)the Key R&D Project of Shandong Province(2022CXPT023)。
文摘Background:Traditional Chinese medicine is promising for managing challenging and complex disorders,including cancer,and in particular,saffron is applied in treating various cancer types.However,its potential therapeutic efficacy and active components in managing squamous cell carcinoma of the head and neck(HNSCC)remain unclear yet.Methods:Using network pharmacology approaches,active ingredients of saffron,their target genes,and HNSCC-related genes were identified.Enrichment analyses were conducted for determining molecular functions and pathways enriched by genes that overlapped between the saffron target gene set and the HNSCC gene set.Among the four known active ingredients of saffron,crocetin was found to have the strongest inhibitory impact on HNSCC,based on the findings of cell viability and migration assays.Therefore,the potential target genes of crocetin in HNSCC cells were examined using molecular docking experiments and were confirmed by qPCR.Result s:Four active ingredients of saffron and 184 of their target genes were identified.Further,a total of 34 overlapping saffron-/HNSCC-associated targets related to the four active ingredients were screened,and crocetin was chosen for further investigation because it had the strongest inhibitory effect on HNSCC cells.Molecular docking experiments indicated that ESR1 and CCND1 were the target genes of crocetin.These results were confirmed through qPCR analysis,in which crocetin was found to lower the expression of the ESR1 and CCND1 genes in AMC-HN-8 and FaDu cells.Conclusion:According to our results,crocetin is a primary active anti-cancer component of saffron that may have potential in the development of novel HNSCC-treating medications.However,more thorough molecular research is necessary for confirming these results and elucidating the anti-cancer mechanism underlying saffron.
基金supported by grants from the National Natural Science Foundation of China (81673393 and 81874308)the Taishan Scholar Program at Shandong Province and the Shandong Natural Science Foundation (ZR2018ZC0233,China)。
文摘Head and neck squamous cell carcinoma(HNSCC) is one of the most common human cancers;however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map(cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of parbendazole, and the direct binding between them was further verified. Parbendazole was further proved as an effective tubulin polymerization inhibitor, which can block the cell cycle, cause apoptosis and prevent cell migration, and it exhibited reasonable therapeutic effect and low toxicity in the in vivo and in vitro anti-tumor evaluation. Our study repositioned an anthelmintic parbendazole to treat HNSCC, which revealed a therapeutic utility and provided a new treatment option for human cancers.
基金supported by the National Natural Science Foundation of China(Grant No.82173303)Natural Science Foundation of Chongqing,China(Grant No.cstc2021ycjh-bgzxm0149).
文摘Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in HPSCC.Methods:In a preceding investigation,HSP90AA1,a differential gene,was discovered through transcriptome sequencing of HPSCC tissues,considering both the presence and absence of LM.Validation of HSP90AA1 expression was accomplished via qRT-PCR,western-blotting(WB),and immunohistochemistry(IHC),while its prognostic significance was assessed employing Kaplan–Meier survival analysis(KMSA),log-rank test(LR),and Cox’s regression analysis(CRA).Bioinformatics techniques facilitated the prediction and analysis of its plausible mechanisms in LM,further substantiated by in vitro and in vivo experiments utilizing FaDu cell lines.Results:HSP90AA1 is substantially upregulated in HPSCC with LM and is identified as an independent prognostic risk determinant.The down-regulation of HSP90AA1 can achieve inhibition of tumor cell proliferation,migration and invasion.Both in vivo experiments and Bioinformatics exploration hint at promoting LM by Epithelial-mesenchymal transition(EMT),regulated by HSP90AA1.Conclusions:HSP90AA1,by controlling EMT,can foster LM in HPSCC.This finding sets the foundation for delving into new therapeutic targets for HPSCC.
基金supported by the National Natural Science Foundation of China(82003228)the Natural Science Foundation of Jiangsu Province(BK20201080)the Research Project of Clinical Medical Science and Technology Development Fund of Jiangsu University(JLY2021097).
文摘Aging is highly associated with tumor formation and progression.However,little research has explored the association of aging-related lncRNAs(ARLs)with the prognosis and tumor immune microenvironment(TIME)of head and neck squamous cell carcinoma(HNSCC).RNA sequences and clinicopathological data of HNSCC patients and normal subjects were downloaded from The Cancer Genome Atlas.In the training group,we used Pearson correlation,univariate Cox regression,least absolute shrinkage/selection operator regression analyses,and multivariate Cox regression to build a prognostic model.In the test group,we evaluated the model.Multivariate Cox regression was done to screen out independent prognostic factors,with which we constructed a nomogram.Afterward,we demonstrated the predictive value of the risk scores based on the model and the nomogram using time-dependent receiver operating characteristics.Gene set enrichment analysis,immune correlation analysis,and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.The most important LINC00861 in the model was examined in HNE1,CNE1,and CNE2 nasopharyngeal carcinoma cell lines and transfected into the cell lines CNE1 and CNE2 using the LINC00861-pcDNA3.1 construct plasmid.In addition,CCK-8,Edu,and SA-β-gal staining assays were conducted to test the biofunction of LINC00861 in the CNE1 and CNE2 cells.The signature based on nine ARLs has a good predictive value in survival time,immune infiltration,immune checkpoint expression,and sensitivity to multiple drugs.LINC00861 expression in CNE2 was significantly lower than in the HNE1 and CNE1 cells,and LINC00861 overexpression significantly inhibited the proliferation and increased the senescence of nasopharyngeal carcinoma cell lines.This work built and verified a new prognostic model for HNSCC based on ARLs and mapped the immune landscape in HNSCC.LINC00861 is a protective factor for the development of HNSCC.
