Objective:Lung cancer is the most common cause of cancer-related deaths worldwide.Platinum-based chemotherapy is one of the main treatment options for patients with non-small cell lung cancer(NSCLC)but the effectivene...Objective:Lung cancer is the most common cause of cancer-related deaths worldwide.Platinum-based chemotherapy is one of the main treatment options for patients with non-small cell lung cancer(NSCLC)but the effectiveness of chemotherapy is encumbered by drug resistance.Therefore,understanding the molecular mechanisms underlying chemotherapy resistance is crucial in improving treatment outcomes and prognosis.Methods:The cell viability assay and apoptosis were used to analyze chemoresistance.Western blot analysis and wound healing testing were used to evaluate the epithelial-to-mesenchymal transition(EMT).Immunoprecipitation was used for analysis of protein modification.Promoter activity was determined using the luciferase reporter assay.Immunofluorescence staining was used to determine reactive oxygen species levels.The expression patterns of EMT markers and carnitine palmitoyltransferase 1C(CPT1C)were determined by Western blot analysis.Results:CPT1C,which was shown to be highly expressed in lung cancer,is associated with cisplatin resistance in NSCLC cells.CPT1C depletion increased NSCLC cell sensitivity to cisplatin,while overexpression of CPT1C increased NSCLC cell resistance to cisplatin.Induction of EMT mediated CPT1C-induced cisplatin resistance.Ectopic expression of Snail reversed the increase in cisplatin sensitivity triggered by CPT1C knockdown.Moreover,CPT1C was shown to be regulated at the post-translational level and an E3-ubiquitin ligase,NEDD4L,was shown to be a major regulator of CPT1C stability and activity.Conclusions:These data provide evidence for the first time that the lipid metabolism enzyme,CPT1C,mediates resistance to chemotherapy.Therefore,the use of combination therapy with a CPT1C inhibitor may be a promising new avenue in lung cancer treatment.展开更多
Heterosis,a crucial biological phenomenon,plays a vital role in determining the yield and quality of plants.Radish,an important root vegetable crop,exhibits notable heterosis in terms of root yield and quality.Neverth...Heterosis,a crucial biological phenomenon,plays a vital role in determining the yield and quality of plants.Radish,an important root vegetable crop,exhibits notable heterosis in terms of root yield and quality.Nevertheless,the molecular mechanism underlying the formation of heterosis in radish remains unclear.Herein,both the transcriptome and DNA methylome analyses were performed on the F_(1)hybrids and parental lines.Expression level dominance(ELD)genes and allele-specific expression(ASE)genes together significantly contribute to heterosis,primarily through energy metabolism and plant hormone signal transduction pathway.An increase in average methylation level in the F_(1)hybrids was observed compared to the parental lines.Interestingly,a negative correlation was found between the methylation level of differentially expressed genes(DEGs)in gene body regions and their expression levels in NAU-LB and the F_(1)hybrids.Moreover,the hybrids were more sensitive to the 5-azacytidine than their parents,and the root weight and total sugar content in the F_(1)hybrids were dramatically decreased compared to the control.Immunolocalization results indicated that the auxin content of the F_(1)hybrids were reduced under 5-azacytidine treatment.Proliferating cell nuclear antigen immunolocalization revealed significant inhibition of vascular cambium activity in both the hybrids and parental lines.Notably,the expression profiles of a few differentially methylated DEGs including RsSUS1,RsSUC2a,RsIAA7,and RsIAA18,were significantly increased in the root of hybrids compared to their parents,suggesting a potential role of DNA methylation in yield heterosis.Collectively,these findings would provide valuable insight into the molecular mechanism underlying taproot yield heterosis and facilitate the genetic improvement of taproot yield and quality in radish breeding programs.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81872371)the Open Project Program of State Key Laboratory of Molecular Oncology(Grant No.SKL-KF-2019-11)+3 种基金the Program for Excellent Sci-tech Innovation Teams of Universities in Anhui Province(Grant No.2023AH010073)the Provincial-level Quality Project in Higher Education Institutions of Anhui Province(Grant No.2022jyxm1710)the College Students Innovation and Entrepreneurship Training Program(Grant No.S202310368028 and S202410368035)the Health Science Research Project of Anhui Province(Grant No.AHWJ2022a028)。
文摘Objective:Lung cancer is the most common cause of cancer-related deaths worldwide.Platinum-based chemotherapy is one of the main treatment options for patients with non-small cell lung cancer(NSCLC)but the effectiveness of chemotherapy is encumbered by drug resistance.Therefore,understanding the molecular mechanisms underlying chemotherapy resistance is crucial in improving treatment outcomes and prognosis.Methods:The cell viability assay and apoptosis were used to analyze chemoresistance.Western blot analysis and wound healing testing were used to evaluate the epithelial-to-mesenchymal transition(EMT).Immunoprecipitation was used for analysis of protein modification.Promoter activity was determined using the luciferase reporter assay.Immunofluorescence staining was used to determine reactive oxygen species levels.The expression patterns of EMT markers and carnitine palmitoyltransferase 1C(CPT1C)were determined by Western blot analysis.Results:CPT1C,which was shown to be highly expressed in lung cancer,is associated with cisplatin resistance in NSCLC cells.CPT1C depletion increased NSCLC cell sensitivity to cisplatin,while overexpression of CPT1C increased NSCLC cell resistance to cisplatin.Induction of EMT mediated CPT1C-induced cisplatin resistance.Ectopic expression of Snail reversed the increase in cisplatin sensitivity triggered by CPT1C knockdown.Moreover,CPT1C was shown to be regulated at the post-translational level and an E3-ubiquitin ligase,NEDD4L,was shown to be a major regulator of CPT1C stability and activity.Conclusions:These data provide evidence for the first time that the lipid metabolism enzyme,CPT1C,mediates resistance to chemotherapy.Therefore,the use of combination therapy with a CPT1C inhibitor may be a promising new avenue in lung cancer treatment.
基金supported by grants from the Jiangsu Seed Industry Revitalization Project[Grant No.JBGS(2021)071]Key Technology R&D Program of Jiangsu Province(Grant No.BE2023366)+3 种基金National Natural Science Foundation of China(Grant No.32172579)the earmarked fund for Jiangsu Agricultural Industry Technology System[Grant No.JATS(2023)421]the Fundamental Research Funds for the Central Universities(Grant No.YDZX2023019)the Project Founded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘Heterosis,a crucial biological phenomenon,plays a vital role in determining the yield and quality of plants.Radish,an important root vegetable crop,exhibits notable heterosis in terms of root yield and quality.Nevertheless,the molecular mechanism underlying the formation of heterosis in radish remains unclear.Herein,both the transcriptome and DNA methylome analyses were performed on the F_(1)hybrids and parental lines.Expression level dominance(ELD)genes and allele-specific expression(ASE)genes together significantly contribute to heterosis,primarily through energy metabolism and plant hormone signal transduction pathway.An increase in average methylation level in the F_(1)hybrids was observed compared to the parental lines.Interestingly,a negative correlation was found between the methylation level of differentially expressed genes(DEGs)in gene body regions and their expression levels in NAU-LB and the F_(1)hybrids.Moreover,the hybrids were more sensitive to the 5-azacytidine than their parents,and the root weight and total sugar content in the F_(1)hybrids were dramatically decreased compared to the control.Immunolocalization results indicated that the auxin content of the F_(1)hybrids were reduced under 5-azacytidine treatment.Proliferating cell nuclear antigen immunolocalization revealed significant inhibition of vascular cambium activity in both the hybrids and parental lines.Notably,the expression profiles of a few differentially methylated DEGs including RsSUS1,RsSUC2a,RsIAA7,and RsIAA18,were significantly increased in the root of hybrids compared to their parents,suggesting a potential role of DNA methylation in yield heterosis.Collectively,these findings would provide valuable insight into the molecular mechanism underlying taproot yield heterosis and facilitate the genetic improvement of taproot yield and quality in radish breeding programs.
