Background:There is increasing evidence that circular RNAs(circRNAs)play a significant role in pathological processes including tumorigenesis.In contrast to exonic circRNAs,which are the most frequently reported circR...Background:There is increasing evidence that circular RNAs(circRNAs)play a significant role in pathological processes including tumorigenesis.In contrast to exonic circRNAs,which are the most frequently reported circRNAs in cancer so far,the studies of intronic circRNAs have been greatly lagged behind.Here,we aimed to investigate the regulatory role of intronic circRNAs in head and neck squamous cell carcinoma(HNSCC).Methods:We conducted whole-transcriptome sequencing with four pairs of primary tumor tissues and adjacent normal tissues from HNSCC patients.Then,we characterized circGNG7 expression in HNSCC tissues and cell lines and explored its association with the prognosis of HNSCC patients.We also identified interactions between circGNG7 and functional proteins,which alter downstream signaling that regulate HNSCC progression.Results:In this study,we identified a new intronic circRNA,circGNG7,and validated its functional roles in HNSCC progression.CircGNG7 was predominately localized to the cytoplasm,and its expression was downregulated in both HNSCC tissues andCAL27,CAL33,SCC4,SCC9,HN6,and HN30 cells.Low expression of circGNG7 was significantly correlated with poor prognosis in HNSCC patients.Consistent with this finding,overexpression of circGNG7 strongly inhibited tumor cell proliferation,colony formation,in vitro migration,and in vivo tumor growth.Mechanistically,the expression of circGNG7 in HNSCC cells was regulated by the transcription factor SMAD family member 4(SMAD4).Importantly,we discovered that circGNG7 could bind to serine residues 78 and 82 of the functional heat shock protein 27(HSP27),occupying its phosphorylation sites and hindering its phosphorylation,which reduced HSP27-JNK/P38 mitogen-activated protein kinase(MAPK)oncogenic signaling.Downregulation of circGNG7 expression in HNSCC increased HSP27-JNK/P38 MAPK signaling and promoted tumor progression.Conclusions:Our results revealed that a new intronic circRNA,circGNG7,functions as a strong tumor suppressor and that circGNG7/HSP27-JNK/P38 MAPK signaling is a novel mechanism by which HNSCC progression can be controlled.展开更多
Background:Highly expressed in various human cancers,circular RNA Protein Kinase C Iota(circPRKCI)has been reported to play an important role in cancer development and progression.Herein,we sought to reveal the progno...Background:Highly expressed in various human cancers,circular RNA Protein Kinase C Iota(circPRKCI)has been reported to play an important role in cancer development and progression.Herein,we sought to reveal the prognostic and clinical value of circPRKCI expression in diverse human cancers.Methods:We searched the Pubmed,Web of Science,and the Cochrane Library databases from inception until May 16,2021.The relationship between circPRKCI expression and cancer patients’survival,including overall survival(OS)and disease-free survival(DFS),was assessed by pooled hazard ratios(HR)with corresponding 95%confidence interval(CI).The correlation between circPRKCI expression and clinical outcomes was evaluated using odds ratios(OR)with corresponding 95%CI.The data were analyzed by STATA software(version 12.0)or Review Manager(RevMan 5.3).Results:A total of 15 studies with 1109 patients were incorporated into our meta-analysis.The results demonstrated that high circPRKCI expression was significantly related to poor OS(HR=1.96,95%CI:1.61,2.39,P<0.001)when compared with low circPRKCI expression in diverse human cancers.However,elevated circPRKCI expression was not associated with DFS(HR=1.34,95%CI:0.93,1.95,P=0.121).Furthermore,the patient with a higher circPRKCI expression was prone to have a larger tumor size,advanced clinical stage,and lymph node metastasis,but it was not significantly correlated with age,gender,and distant metastasis.Conclusion:Elevated circPRKCI expression was correlated with worse OS and unfavorable clinical features,suggesting a novel prognostic and predictive role of circPRKCI in diverse human cancers.展开更多
Background and Aims:Hepatocellular carcinoma(HCC)is one of the most fatal malignancies.Epigenetic mechanisms have revealed that noncoding RNAs,such as microRNAs(miRNAs)and circular RNAs(circRNAs),are involved in HCC p...Background and Aims:Hepatocellular carcinoma(HCC)is one of the most fatal malignancies.Epigenetic mechanisms have revealed that noncoding RNAs,such as microRNAs(miRNAs)and circular RNAs(circRNAs),are involved in HCC progression.This study aimed to construct a circRNA-miRNAmRNA network in HCC and validate one axis within the network.Methods:HCC-related transcriptome data were obtained from the Gene Expression Omnibus,and HCC-related genes were sourced from GeneCards to identify differentially expressed circRNAs and miRNAs.The targeting relationships between circRNA-miRNA and miRNA-mRNA interactions were predicted.The involvement of the hsa_circ_0001726/miR-140-3p/KRAS axis in HCC was evaluated through cellular experiments and survival analyses.Results:We identified six differentially expressed circRNAs in HCC,which were linked to 13 miRNAs and 88 mRNAs.A network containing 34 circRNA-miRNA pairs and 194 miRNA-mRNA pairs was constructed.Cell proliferation and migration assays confirmed the role of hsa_circ_0001726 in promoting HCC progression,possibly through the miR-140-3p/KRAS axis.Survival analysis verified that hsa_circ_0001726 was a prognostic factor for overall survival in patients with HCC.The hsa_circ_0001726/miR-140-3p/KRAS axis also mediates lenvatinib resistance in HCC cells.Conclusions:The HCC circRNA/miRNA/mRNA network provides new insights into the post-transcriptional regulatory mechanism of HCC.The hsa_circ_0001726/miR-140-3p/KRAS axis is involved in HCC progression and lenvatinib resistance.展开更多
基金This study was supported by grants from the National Natural Science Foundation of China(No.81902748 and 81872185)Shanghai Sailing Program(No.19YF1427100)sponsored by Program of Innovative Research Team of High-level Local Universities in Shanghai.
文摘Background:There is increasing evidence that circular RNAs(circRNAs)play a significant role in pathological processes including tumorigenesis.In contrast to exonic circRNAs,which are the most frequently reported circRNAs in cancer so far,the studies of intronic circRNAs have been greatly lagged behind.Here,we aimed to investigate the regulatory role of intronic circRNAs in head and neck squamous cell carcinoma(HNSCC).Methods:We conducted whole-transcriptome sequencing with four pairs of primary tumor tissues and adjacent normal tissues from HNSCC patients.Then,we characterized circGNG7 expression in HNSCC tissues and cell lines and explored its association with the prognosis of HNSCC patients.We also identified interactions between circGNG7 and functional proteins,which alter downstream signaling that regulate HNSCC progression.Results:In this study,we identified a new intronic circRNA,circGNG7,and validated its functional roles in HNSCC progression.CircGNG7 was predominately localized to the cytoplasm,and its expression was downregulated in both HNSCC tissues andCAL27,CAL33,SCC4,SCC9,HN6,and HN30 cells.Low expression of circGNG7 was significantly correlated with poor prognosis in HNSCC patients.Consistent with this finding,overexpression of circGNG7 strongly inhibited tumor cell proliferation,colony formation,in vitro migration,and in vivo tumor growth.Mechanistically,the expression of circGNG7 in HNSCC cells was regulated by the transcription factor SMAD family member 4(SMAD4).Importantly,we discovered that circGNG7 could bind to serine residues 78 and 82 of the functional heat shock protein 27(HSP27),occupying its phosphorylation sites and hindering its phosphorylation,which reduced HSP27-JNK/P38 mitogen-activated protein kinase(MAPK)oncogenic signaling.Downregulation of circGNG7 expression in HNSCC increased HSP27-JNK/P38 MAPK signaling and promoted tumor progression.Conclusions:Our results revealed that a new intronic circRNA,circGNG7,functions as a strong tumor suppressor and that circGNG7/HSP27-JNK/P38 MAPK signaling is a novel mechanism by which HNSCC progression can be controlled.
基金supported by grants from the National Natural Science Foundation of China(Nos.81902745,82172500,82272664,and 82103228)Hunan Provincial Innovation Foundation for Post-graduate(No.CX20190160)China Postdoctoral Science Foundation(No.2021M693557)
文摘Background:Highly expressed in various human cancers,circular RNA Protein Kinase C Iota(circPRKCI)has been reported to play an important role in cancer development and progression.Herein,we sought to reveal the prognostic and clinical value of circPRKCI expression in diverse human cancers.Methods:We searched the Pubmed,Web of Science,and the Cochrane Library databases from inception until May 16,2021.The relationship between circPRKCI expression and cancer patients’survival,including overall survival(OS)and disease-free survival(DFS),was assessed by pooled hazard ratios(HR)with corresponding 95%confidence interval(CI).The correlation between circPRKCI expression and clinical outcomes was evaluated using odds ratios(OR)with corresponding 95%CI.The data were analyzed by STATA software(version 12.0)or Review Manager(RevMan 5.3).Results:A total of 15 studies with 1109 patients were incorporated into our meta-analysis.The results demonstrated that high circPRKCI expression was significantly related to poor OS(HR=1.96,95%CI:1.61,2.39,P<0.001)when compared with low circPRKCI expression in diverse human cancers.However,elevated circPRKCI expression was not associated with DFS(HR=1.34,95%CI:0.93,1.95,P=0.121).Furthermore,the patient with a higher circPRKCI expression was prone to have a larger tumor size,advanced clinical stage,and lymph node metastasis,but it was not significantly correlated with age,gender,and distant metastasis.Conclusion:Elevated circPRKCI expression was correlated with worse OS and unfavorable clinical features,suggesting a novel prognostic and predictive role of circPRKCI in diverse human cancers.
基金supported by the Fujian Natural Science Foundation Project(General)[Grant number:2021J011265]the Fund for Scientific Research Projects of the Organ Transplantation Section of the Joint Logistics Support Force Key Discipline of Joint Logistics Medicine[Grant number:LQZDQG].
文摘Background and Aims:Hepatocellular carcinoma(HCC)is one of the most fatal malignancies.Epigenetic mechanisms have revealed that noncoding RNAs,such as microRNAs(miRNAs)and circular RNAs(circRNAs),are involved in HCC progression.This study aimed to construct a circRNA-miRNAmRNA network in HCC and validate one axis within the network.Methods:HCC-related transcriptome data were obtained from the Gene Expression Omnibus,and HCC-related genes were sourced from GeneCards to identify differentially expressed circRNAs and miRNAs.The targeting relationships between circRNA-miRNA and miRNA-mRNA interactions were predicted.The involvement of the hsa_circ_0001726/miR-140-3p/KRAS axis in HCC was evaluated through cellular experiments and survival analyses.Results:We identified six differentially expressed circRNAs in HCC,which were linked to 13 miRNAs and 88 mRNAs.A network containing 34 circRNA-miRNA pairs and 194 miRNA-mRNA pairs was constructed.Cell proliferation and migration assays confirmed the role of hsa_circ_0001726 in promoting HCC progression,possibly through the miR-140-3p/KRAS axis.Survival analysis verified that hsa_circ_0001726 was a prognostic factor for overall survival in patients with HCC.The hsa_circ_0001726/miR-140-3p/KRAS axis also mediates lenvatinib resistance in HCC cells.Conclusions:The HCC circRNA/miRNA/mRNA network provides new insights into the post-transcriptional regulatory mechanism of HCC.The hsa_circ_0001726/miR-140-3p/KRAS axis is involved in HCC progression and lenvatinib resistance.
