Objective The initiation and progression of lung carcinomas are critically regulated by long non-coding RNAs(lncRNAs).However,the role of lncRNAs in the pathways causing lung cancer remains unknown.Methods Cell morpho...Objective The initiation and progression of lung carcinomas are critically regulated by long non-coding RNAs(lncRNAs).However,the role of lncRNAs in the pathways causing lung cancer remains unknown.Methods Cell morphology was regularly observed using an inverted phase-contrast microscope.Cell viability was assessed using CCK-8 according to the manufacturer’s instructions.Total RNA was retrotranscribed from each specimen using the RNAiso Plus Kit.The RT-PCR data were calculated using the Ct approach for comparison.Flow cytometric analyses were prepared by Click-iT™Plus TUNEL Assay for In Situ apoptosis detection,with Alexa Fluor^(TM)594 dye,as instructed.RNA immunoprecipitation assays were used to determine RNA concentration.Results Activated natural killer cells repeat and PH domain-containing protein 2 antisense RNA 1(AGAP2-AS1)levels in cancerous tissues were significantly correlated with cancerous tumor node metastasis(TNM)stage,with cancerous AGAP2-AS1 levels being higher in cancerous tissues than healthy tissues.Patients withelevated AGAP2-AS1 levels had considerably worse outcomes than those with reduced AGAP2-AS1 levels,regardless of the progression-free or overall survival.Functionally,AGAP2-AS1 downregulation represseslung cancer cell growth.AGAP2-AS1 elimination induces erastin-mediated ferroptosis in lung cancer cells.However,the ferritin inhibitor FERSINT-1 negated this result,whereas ERASTIN induced lung cancer cellmortality.After AGAP2-AS1 silencing,erastin-treated lung cancer cells showed a remarkable decrease inGSH levels.These results indicated that AGAP2-AS1 enhanced the stabilization of SLC7A11 mRNA via Recombinant Insulin Like Growth Factor Binding Protein 2(IGF BP2).Patients with elevated AGAP2-AS1 had considerably worse outcomes.Down-regulating AGAP2-AS1 was able to repress lung cancer cell growth and induce greater Erastin-mediated ferroptosis.Lungcancer cells treated with Erastin exhibited a remarkable decrease inglutathione(GSH)levels.The mechanical findingsindicated that AGAP2-AS1 enhanced the stabilization of SLC7A11 mRNA via the IGF2BP2.Conclusion We identified a novel effect of AGAP2-AS1 on TNM staging and the prognosis of patientswith lungcancer by modulating SLC7A11 mRNA stability and ferroptosis.展开更多
BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl di...BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI)revealed the nodule in S5 with a defect at the hepatobiliary phase,hyperintensity on diffusion weighted imaging(DWI)and hypointensity on apparent diffusion coefficient(ADC)map.Contrast-enhanced computed tomography revealed hypervascularity at the early phase,and delayed contrast-enhancement was observed at the late phase.Contrast-enhanced ultrasound(US)revealed incomplete defect at the late vascular phase.Inflammatory liver tumor,lymphoproliferative disease,intrahepatic cholangiocarcinoma(small duct type)and bile duct adenoma were suspected through the imaging studies.US guided biopsy,however,showed a noncaseating hepatic sarcoid-like epithelioid granuloma(HSEG),and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells.One month after admission,EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase,of hyperintensity on DWI,of hypointensity on ADC map,and no stain at the early phase.CONCLUSION That the patient had received BNT162b2 messenger RNA(mRNA)coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG,and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction(DISR)might be induced by the mRNA vaccination.Fortunately,rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.展开更多
基金Supported by the Wuhan Municipal Health Commission Medical Research Project-Youth Project(No.WZ20Q04).
文摘Objective The initiation and progression of lung carcinomas are critically regulated by long non-coding RNAs(lncRNAs).However,the role of lncRNAs in the pathways causing lung cancer remains unknown.Methods Cell morphology was regularly observed using an inverted phase-contrast microscope.Cell viability was assessed using CCK-8 according to the manufacturer’s instructions.Total RNA was retrotranscribed from each specimen using the RNAiso Plus Kit.The RT-PCR data were calculated using the Ct approach for comparison.Flow cytometric analyses were prepared by Click-iT™Plus TUNEL Assay for In Situ apoptosis detection,with Alexa Fluor^(TM)594 dye,as instructed.RNA immunoprecipitation assays were used to determine RNA concentration.Results Activated natural killer cells repeat and PH domain-containing protein 2 antisense RNA 1(AGAP2-AS1)levels in cancerous tissues were significantly correlated with cancerous tumor node metastasis(TNM)stage,with cancerous AGAP2-AS1 levels being higher in cancerous tissues than healthy tissues.Patients withelevated AGAP2-AS1 levels had considerably worse outcomes than those with reduced AGAP2-AS1 levels,regardless of the progression-free or overall survival.Functionally,AGAP2-AS1 downregulation represseslung cancer cell growth.AGAP2-AS1 elimination induces erastin-mediated ferroptosis in lung cancer cells.However,the ferritin inhibitor FERSINT-1 negated this result,whereas ERASTIN induced lung cancer cellmortality.After AGAP2-AS1 silencing,erastin-treated lung cancer cells showed a remarkable decrease inGSH levels.These results indicated that AGAP2-AS1 enhanced the stabilization of SLC7A11 mRNA via Recombinant Insulin Like Growth Factor Binding Protein 2(IGF BP2).Patients with elevated AGAP2-AS1 had considerably worse outcomes.Down-regulating AGAP2-AS1 was able to repress lung cancer cell growth and induce greater Erastin-mediated ferroptosis.Lungcancer cells treated with Erastin exhibited a remarkable decrease inglutathione(GSH)levels.The mechanical findingsindicated that AGAP2-AS1 enhanced the stabilization of SLC7A11 mRNA via the IGF2BP2.Conclusion We identified a novel effect of AGAP2-AS1 on TNM staging and the prognosis of patientswith lungcancer by modulating SLC7A11 mRNA stability and ferroptosis.
文摘BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI)revealed the nodule in S5 with a defect at the hepatobiliary phase,hyperintensity on diffusion weighted imaging(DWI)and hypointensity on apparent diffusion coefficient(ADC)map.Contrast-enhanced computed tomography revealed hypervascularity at the early phase,and delayed contrast-enhancement was observed at the late phase.Contrast-enhanced ultrasound(US)revealed incomplete defect at the late vascular phase.Inflammatory liver tumor,lymphoproliferative disease,intrahepatic cholangiocarcinoma(small duct type)and bile duct adenoma were suspected through the imaging studies.US guided biopsy,however,showed a noncaseating hepatic sarcoid-like epithelioid granuloma(HSEG),and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells.One month after admission,EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase,of hyperintensity on DWI,of hypointensity on ADC map,and no stain at the early phase.CONCLUSION That the patient had received BNT162b2 messenger RNA(mRNA)coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG,and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction(DISR)might be induced by the mRNA vaccination.Fortunately,rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.