Background:The long noncoding RNA HOTTIP has recently been described as a biomarker of poor prognosis in patients with hepatocellular carcinoma(HCC).Methods:In the present study,we evaluated the clinical significance ...Background:The long noncoding RNA HOTTIP has recently been described as a biomarker of poor prognosis in patients with hepatocellular carcinoma(HCC).Methods:In the present study,we evaluated the clinical significance of HOTTIP expression in predicting the rate of tumor recurrence in HCC patients after liver transplantation(LT).We examined the expression pattern and single nucleotide polymorphism(SNP)genotype of HOTTIP in HCC samples from 155 patients underwent LT,and its correlation with clinical parameters and patient prognosis was analyzed.HOTTIP was suppressed using siRNA to explore the role HOTTIP plays in tumor progression.Results:The expression level of HOTTIP in cancer tissues was higher than in adjacent noncancerous tissues.Multivariate analyses revealed that HOTTIP expression was an independent prognostic factor for tumor recurrence and lower overall survival times in HCC patients after LT.Patients who beyond the Milan criteria and exhibit decreased HOTTIP expression experienced longer recurrence-free survival and overall survival.HOTTIP rs2071265 is associated with an earlier recurrence in HCC patients.Moreover,the suppression of HOTTIP in liver cancer cell lines reduced cell invasion rates and increased chemosensitivity.Conclusions:In summary,the high expression level of HOTTIP in HCC could serve as a candidate biomarker for predicting poor prognosis in HCC patients underwent liver transplant therapy.Furthermore,HOTTIP might be a potential therapeutic target.展开更多
HOXA transcript at the distal tip(HOTTIP),a newly identified long noncoding RNA,has been shown to exhibit anti-inflammatory effects and inhibit oxygen-glucose deprivation-induced neuronal apoptosis.However,its role in...HOXA transcript at the distal tip(HOTTIP),a newly identified long noncoding RNA,has been shown to exhibit anti-inflammatory effects and inhibit oxygen-glucose deprivation-induced neuronal apoptosis.However,its role in Parkinson's disease(PD)remains unclear.1-Methyl-4-phenylpyridium(MPP+)and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)were used to establish PD models in SH-SY5 Y and BV2 cells and in C57 BL/6 male mice,respectively.In vitro,after HOTTIP knockdown by sh-HOTTIP transfection,HOTTIP and FOXO1 overexpression promoted SH-SY5 Y apoptosis,BV2 microglial activation,proinflammatory cytokine expression,and nuclear factor kappa-B and NACHT,LRR and PYD domains-containing protein 3 inflammasome activation.Overexpression of mi R-615-3 p inhibited MPP+-induced neuronal apoptosis and microglial inflammation and ameliorated HOTTIP-and FOXO1-mediated nerve injury and inflammation.In vivo,HOTTIP knockdown alleviated motor dysfunction in PD mice and reduced neuronal apoptosis and microglial activation in the substantia nigra.These findings suggest that inhibition of HOTTIP mitigates neuronal apoptosis and microglial activation in PD models by modulating mi R-615-3 p/FOXO1.This study was approved by the Ethics Review Committee of the Affiliated Hospital of Qingdao University,China(approval No.UDX-2018-042)in June 2018.展开更多
基金This study was supported by the Key Research Development Program of Zhejiang Province(No.2018C03018)the Technology Research Program of Jiaxing(Grant No.2015AY23013).
文摘Background:The long noncoding RNA HOTTIP has recently been described as a biomarker of poor prognosis in patients with hepatocellular carcinoma(HCC).Methods:In the present study,we evaluated the clinical significance of HOTTIP expression in predicting the rate of tumor recurrence in HCC patients after liver transplantation(LT).We examined the expression pattern and single nucleotide polymorphism(SNP)genotype of HOTTIP in HCC samples from 155 patients underwent LT,and its correlation with clinical parameters and patient prognosis was analyzed.HOTTIP was suppressed using siRNA to explore the role HOTTIP plays in tumor progression.Results:The expression level of HOTTIP in cancer tissues was higher than in adjacent noncancerous tissues.Multivariate analyses revealed that HOTTIP expression was an independent prognostic factor for tumor recurrence and lower overall survival times in HCC patients after LT.Patients who beyond the Milan criteria and exhibit decreased HOTTIP expression experienced longer recurrence-free survival and overall survival.HOTTIP rs2071265 is associated with an earlier recurrence in HCC patients.Moreover,the suppression of HOTTIP in liver cancer cell lines reduced cell invasion rates and increased chemosensitivity.Conclusions:In summary,the high expression level of HOTTIP in HCC could serve as a candidate biomarker for predicting poor prognosis in HCC patients underwent liver transplant therapy.Furthermore,HOTTIP might be a potential therapeutic target.
文摘HOXA transcript at the distal tip(HOTTIP),a newly identified long noncoding RNA,has been shown to exhibit anti-inflammatory effects and inhibit oxygen-glucose deprivation-induced neuronal apoptosis.However,its role in Parkinson's disease(PD)remains unclear.1-Methyl-4-phenylpyridium(MPP+)and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)were used to establish PD models in SH-SY5 Y and BV2 cells and in C57 BL/6 male mice,respectively.In vitro,after HOTTIP knockdown by sh-HOTTIP transfection,HOTTIP and FOXO1 overexpression promoted SH-SY5 Y apoptosis,BV2 microglial activation,proinflammatory cytokine expression,and nuclear factor kappa-B and NACHT,LRR and PYD domains-containing protein 3 inflammasome activation.Overexpression of mi R-615-3 p inhibited MPP+-induced neuronal apoptosis and microglial inflammation and ameliorated HOTTIP-and FOXO1-mediated nerve injury and inflammation.In vivo,HOTTIP knockdown alleviated motor dysfunction in PD mice and reduced neuronal apoptosis and microglial activation in the substantia nigra.These findings suggest that inhibition of HOTTIP mitigates neuronal apoptosis and microglial activation in PD models by modulating mi R-615-3 p/FOXO1.This study was approved by the Ethics Review Committee of the Affiliated Hospital of Qingdao University,China(approval No.UDX-2018-042)in June 2018.
