BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
Background:In regard to head and neck squamous cell carcinoma(HNSC),a common type of head and neck malignant tumor with high mortality,the role of Piezo-type mechanosensitive ion channel component 1(PIEZO1)is poorly u...Background:In regard to head and neck squamous cell carcinoma(HNSC),a common type of head and neck malignant tumor with high mortality,the role of Piezo-type mechanosensitive ion channel component 1(PIEZO1)is poorly understood.PIEZO1,a mechanosensitive ion channel,is implicated in tumorigenesis,but its expression,prognostic significance,and mechanisms in HNSC remain unclear.Our study aimed to clarify these aspects through in vitro experiments and bioinformatics analyses.Methods:In order to investigate PIEZO1 expression in normal and cancerous tissues,we used The Cancer Genome Atlas data.Our bioinformatics analyses explored PIEZO1 mRNA expression,correlations,survival curves,upstream mRNA targets,and coexpressed genes.Gene Ontology analysis functionally annotated these coexpressed genes,and pathway enrichment studies further clarified their roles.In addition,we conducted in vitro experiments to examine and compare PIEZO1 expression in normal and cancerous human tissue samples.We performed immunohistochemical analyses to detect PIEZO1 expression in human HNSC tissues.Results:Our results have revealed significantly elevated PIEZO1 expression in HNSC tissue samples compared with adjacent noncancerous tissues.Bioinformatics analysis further showed that PIEZO1 expression was notably higher in high-grade HNSC tumors and was associated with lower survival rates.OncomiR database analysis showed that the downregulation of hsa-miR-101-3p correlated with increased PIEZO1 expression in HNSC.Mechanistic studies identified 4 focal adhesion-related genes(ITGA5,LAMC2,PXN,and VEGFC)modulated by PIEZO1.These findings underscore the potential of PIEZO1 as a therapeutic target and prognostic marker for HNSC.Conclusions:Our study has revealed the expression profile of PIEZO1 in HNSC,emphasizing its potential as a diagnostic and therapeutic target along with hsa-miR-101-3p.展开更多
miR-101a-3p is expressed in a variety of organs and tissues and plays a regulatory role in many diseases,but its role in spinal cord ischemia/reperfusion injury remains unclear.In this study,we established a rat model...miR-101a-3p is expressed in a variety of organs and tissues and plays a regulatory role in many diseases,but its role in spinal cord ischemia/reperfusion injury remains unclear.In this study,we established a rat model of spinal cord ischemia/reperfusion injury by clamping the aortic arch for 14 minutes followed by reperfusion for 24 hours.Results showed that miR-101a-3p expression in L4-L6 spinal cord was greatly decreased,whereas MYCN expression was greatly increased.Dual-luciferase reporter assay results showed that miR-101a-3p targeted MYCN.MYCN immunoreactivity,which was primarily colocalized with neurons in L4-L6 spinal tissue,greatly increased after spinal cord ischemia/reperfusion injury.However,intrathecal injection of an miR-101a-3p mimic within 24 hours before injury decreased MYCN,p53,caspase-9 and interleukin-1βexpression,reduced p53 immunoreactivity,reduced the number of MYCN/NeuN-positive cells and the number of necrotic cells in L4-L6 spinal tissue,and increased Tarlov scores.These findings suggest that the miR-101a-3p mimic improved spinal ischemia/reperfusion injury-induced nerve cell apoptosis and inflammation by inhibiting MYCN and the p53 signaling pathway.Therefore,miR-101a-3p mimic therapy may be a potential treatment option for spinal ischemia/reperfusion injury.展开更多
基金Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBJC00001the Key Discipline Special Project of Tianjin Municipal Health Commission,No.TJWJ2022XK016.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.
基金supported by grants from Hefei Municipal Health Commission,Hefei Municipal Finance Bureau(No.[2023]72).
文摘Background:In regard to head and neck squamous cell carcinoma(HNSC),a common type of head and neck malignant tumor with high mortality,the role of Piezo-type mechanosensitive ion channel component 1(PIEZO1)is poorly understood.PIEZO1,a mechanosensitive ion channel,is implicated in tumorigenesis,but its expression,prognostic significance,and mechanisms in HNSC remain unclear.Our study aimed to clarify these aspects through in vitro experiments and bioinformatics analyses.Methods:In order to investigate PIEZO1 expression in normal and cancerous tissues,we used The Cancer Genome Atlas data.Our bioinformatics analyses explored PIEZO1 mRNA expression,correlations,survival curves,upstream mRNA targets,and coexpressed genes.Gene Ontology analysis functionally annotated these coexpressed genes,and pathway enrichment studies further clarified their roles.In addition,we conducted in vitro experiments to examine and compare PIEZO1 expression in normal and cancerous human tissue samples.We performed immunohistochemical analyses to detect PIEZO1 expression in human HNSC tissues.Results:Our results have revealed significantly elevated PIEZO1 expression in HNSC tissue samples compared with adjacent noncancerous tissues.Bioinformatics analysis further showed that PIEZO1 expression was notably higher in high-grade HNSC tumors and was associated with lower survival rates.OncomiR database analysis showed that the downregulation of hsa-miR-101-3p correlated with increased PIEZO1 expression in HNSC.Mechanistic studies identified 4 focal adhesion-related genes(ITGA5,LAMC2,PXN,and VEGFC)modulated by PIEZO1.These findings underscore the potential of PIEZO1 as a therapeutic target and prognostic marker for HNSC.Conclusions:Our study has revealed the expression profile of PIEZO1 in HNSC,emphasizing its potential as a diagnostic and therapeutic target along with hsa-miR-101-3p.
文摘miR-101a-3p is expressed in a variety of organs and tissues and plays a regulatory role in many diseases,but its role in spinal cord ischemia/reperfusion injury remains unclear.In this study,we established a rat model of spinal cord ischemia/reperfusion injury by clamping the aortic arch for 14 minutes followed by reperfusion for 24 hours.Results showed that miR-101a-3p expression in L4-L6 spinal cord was greatly decreased,whereas MYCN expression was greatly increased.Dual-luciferase reporter assay results showed that miR-101a-3p targeted MYCN.MYCN immunoreactivity,which was primarily colocalized with neurons in L4-L6 spinal tissue,greatly increased after spinal cord ischemia/reperfusion injury.However,intrathecal injection of an miR-101a-3p mimic within 24 hours before injury decreased MYCN,p53,caspase-9 and interleukin-1βexpression,reduced p53 immunoreactivity,reduced the number of MYCN/NeuN-positive cells and the number of necrotic cells in L4-L6 spinal tissue,and increased Tarlov scores.These findings suggest that the miR-101a-3p mimic improved spinal ischemia/reperfusion injury-induced nerve cell apoptosis and inflammation by inhibiting MYCN and the p53 signaling pathway.Therefore,miR-101a-3p mimic therapy may be a potential treatment option for spinal ischemia/reperfusion injury.
