目的探究肌球蛋白重链11(myosin heavy chain 11,MYH11)对喉鳞状细胞癌细胞恶性生物学行为的影响及机制。方法qRT-PCR检测MYH11 mRNA在喉鳞状细胞癌组织以及喉鳞状细胞癌细胞中的表达。喉鳞状细胞癌细胞TU686分为si-MYH11组和si-NC组。F...目的探究肌球蛋白重链11(myosin heavy chain 11,MYH11)对喉鳞状细胞癌细胞恶性生物学行为的影响及机制。方法qRT-PCR检测MYH11 mRNA在喉鳞状细胞癌组织以及喉鳞状细胞癌细胞中的表达。喉鳞状细胞癌细胞TU686分为si-MYH11组和si-NC组。FD-LSC-1细胞分为MYH11组和Vector组。CCK8、流式细胞术、细胞划痕、Transwell实验分别用于检测细胞增殖、凋亡、迁移以及侵袭能力,蛋白质印迹检测各组细胞ERK 1/2磷酸化水平及MAPK相对表达量。结果MYH11高表达于喉鳞状细胞癌组织及细胞。si-MYH11组TU686细胞增殖、迁移和侵袭能力显著低于si-NC组(P_(均)<0.05),细胞凋亡显著高于si-NC组(P<0.01),ERK1/2磷酸化水平及MAPK表达显著低于si-NC组(P<0.01)。MYH11组TU686细胞增殖、迁移和侵袭能力显著高于Vector组(P_(均)<0.05),细胞凋亡显著低于Vector组(P<0.01),ERK1/2磷酸化水平及MAPK表达显著高于Vector组(P<0.01)。结论MYH11激活ERK/MAPK信号通路而促进喉鳞状细胞癌细胞的增殖、迁移和侵袭能力。展开更多
BACKGROUND Chronic intestinal pseudo-obstruction(CIPO)is a rare and debilitating disorder,characterized by severe impairments in gastrointestinal motility.The affected sites include the enteric/intrinsic autonomic ner...BACKGROUND Chronic intestinal pseudo-obstruction(CIPO)is a rare and debilitating disorder,characterized by severe impairments in gastrointestinal motility.The affected sites include the enteric/intrinsic autonomic nerves(neuropathy),intestinal smooth muscle cells(myopathy),and interstitial cells of Cajal(mesenchymopathy).The etiology can be genetic,idiopathic,or acquired.Owing to its nonspecific clinical presentation and lack of definitive diagnostic methods,misdiagnosis of CIPO is common.CASE SUMMARY This case involved an older male with insidious onset in adolescence who presented with postprandial bloating,intermittent diarrhea,and weight loss.During the disease course,the patient experienced two episodes of intestinal obstruction.Imaging revealed multisegmental digestive tract abnormalities(gastric emptying disorder,significant duodenal dilatation,and segmental jejunal dilatation).Whole-exome sequencing revealed a rare MYH11 mutation[NM_0010-40113.2:C.5819del(p.Pro1940HisfsTer91)],confirming hereditary myopathic CIPO.CONCLUSION This report adds to our current understanding of CIPO etiology by reinforcing the role of MYH11 variants in the pathogenesis of the CIPO phenotype.展开更多
Background:Colorectal cancer(CRC)is common and deadly,often leading to metastasis,challenging treatment,and poor outcomes.Understanding its molecular basis is crucial for developing effective therapies.Aims:This study...Background:Colorectal cancer(CRC)is common and deadly,often leading to metastasis,challenging treatment,and poor outcomes.Understanding its molecular basis is crucial for developing effective therapies.Aims:This study aimed to investigate the role of Myosin Heavy Chain 11(MYH11)in CRC progression,especially its effects on epithelial-mesenchymal transition(EMT)and cell behavior,and to explore its potential regulation by the EMT transcription factor zinc finger E-box binding homeobox 1(ZEB1).Methods:Differential expression analysis was performed in the GSE123390 and TCGA-READ datasets,and 317 intersection genes were identified.The hub gene MYH11 was identified based on Protein-protein interaction(PPI)analysis and expression validation.The effects of MYH11 and the EMT transcription factor(ZEB1)on the behavior of CRC cells were investigated in vitro.Results:Bioinformatics research revealed that MYH11 was considerably downregulated in CRC samples as compared to normal samples.Overexpression of MYH11 inhibited the proliferation,migration,and invasion of CRC cells.Western blotting(WB)testing showed that MYH11 overexpression inhibited EMT by elevating E-cadherin levels while suppressing ZEB1,vimentin,and N-cadherin expressions.By contrast,overexpression of ZEB1 promoted EMT and enhanced migration,invasion,and proliferation of CRC cells.The negative impacts of MYH11 affecting EMT markers and cell behaviors were partially mitigated by co-overexpression of MYH11 and ZEB1,indicating that MYH11 regulates EMT and CRC progression through ZEB1.Conclusion:Our study shows MYH11 curbs CRC growth by blocking EMT and invasion,but ZEB1 overexpression reduces this effect.It uncovers key CRC pathways and suggests MYH11’s therapeutic potential.展开更多
基金Supported by The National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-129.
文摘BACKGROUND Chronic intestinal pseudo-obstruction(CIPO)is a rare and debilitating disorder,characterized by severe impairments in gastrointestinal motility.The affected sites include the enteric/intrinsic autonomic nerves(neuropathy),intestinal smooth muscle cells(myopathy),and interstitial cells of Cajal(mesenchymopathy).The etiology can be genetic,idiopathic,or acquired.Owing to its nonspecific clinical presentation and lack of definitive diagnostic methods,misdiagnosis of CIPO is common.CASE SUMMARY This case involved an older male with insidious onset in adolescence who presented with postprandial bloating,intermittent diarrhea,and weight loss.During the disease course,the patient experienced two episodes of intestinal obstruction.Imaging revealed multisegmental digestive tract abnormalities(gastric emptying disorder,significant duodenal dilatation,and segmental jejunal dilatation).Whole-exome sequencing revealed a rare MYH11 mutation[NM_0010-40113.2:C.5819del(p.Pro1940HisfsTer91)],confirming hereditary myopathic CIPO.CONCLUSION This report adds to our current understanding of CIPO etiology by reinforcing the role of MYH11 variants in the pathogenesis of the CIPO phenotype.
基金funded by Outstanding Leaders Training Programof Pudong Health Commission of Shanghai(No.PWR12023-03)In-house Project of Shanghai Pudong NewArea People’sHospital(No.E24-02).
文摘Background:Colorectal cancer(CRC)is common and deadly,often leading to metastasis,challenging treatment,and poor outcomes.Understanding its molecular basis is crucial for developing effective therapies.Aims:This study aimed to investigate the role of Myosin Heavy Chain 11(MYH11)in CRC progression,especially its effects on epithelial-mesenchymal transition(EMT)and cell behavior,and to explore its potential regulation by the EMT transcription factor zinc finger E-box binding homeobox 1(ZEB1).Methods:Differential expression analysis was performed in the GSE123390 and TCGA-READ datasets,and 317 intersection genes were identified.The hub gene MYH11 was identified based on Protein-protein interaction(PPI)analysis and expression validation.The effects of MYH11 and the EMT transcription factor(ZEB1)on the behavior of CRC cells were investigated in vitro.Results:Bioinformatics research revealed that MYH11 was considerably downregulated in CRC samples as compared to normal samples.Overexpression of MYH11 inhibited the proliferation,migration,and invasion of CRC cells.Western blotting(WB)testing showed that MYH11 overexpression inhibited EMT by elevating E-cadherin levels while suppressing ZEB1,vimentin,and N-cadherin expressions.By contrast,overexpression of ZEB1 promoted EMT and enhanced migration,invasion,and proliferation of CRC cells.The negative impacts of MYH11 affecting EMT markers and cell behaviors were partially mitigated by co-overexpression of MYH11 and ZEB1,indicating that MYH11 regulates EMT and CRC progression through ZEB1.Conclusion:Our study shows MYH11 curbs CRC growth by blocking EMT and invasion,but ZEB1 overexpression reduces this effect.It uncovers key CRC pathways and suggests MYH11’s therapeutic potential.
