Background:Liver cancer stem cells(LCSCs)are recognized as pivotal drivers of hepatocellular carcinoma(HCC)progression;however,the molecular mechanisms maintaining their stem-like phenotype remain largely unresolved.T...Background:Liver cancer stem cells(LCSCs)are recognized as pivotal drivers of hepatocellular carcinoma(HCC)progression;however,the molecular mechanisms maintaining their stem-like phenotype remain largely unresolved.This work investigates the role of prefoldin subunit 6-like protein(PFDN6L)in shaping LCSC traits and promoting or restraining HCC progression.Methods:PFDN6L,a cytoskeleton-associated chaperone,was studied using multiple in vitro assays—cell growth evaluation,cell cycle profiling,and spheroid culture—alongside analyses of stemness-associated markers(SOX2,CD133,CD44).Tumorigenic capacity was assessed in xenograft mouse models,and signaling pathway interrogation was performed to define underlying mechanisms.Results:In patient samples,higher PFDN6L expression correlated with improved survival outcomes.Forced expression of PFDN6L induced G2/M arrest,diminished sphere formation,and reduced pluripotency marker expression,whereas knockdown accelerated in vivo tumor formation.Mechanistic experiments demonstrated that PFDN6L suppressesmalignancy by simultaneously dampening AKT and ERK1/2 activation,thereby impairing oncogenic signaling cascades.Conclusion:PFDN6L acts as a negative regulator of LCSC-driven tumorigenesis.Its dual blockade of AKT and ERK pathways forms the mechanistic basis of its tumor-suppressive action,supporting its potential as a prognostic biomarker and therapeutic target in HCC.展开更多
Objective Colorectal cancer(CRC)is a common cancer worldwide.Although there are several treatments for cancer,the therapeutic effect on CRC remains unsatisfactory,and it is imperative to identify new therapeutic targe...Objective Colorectal cancer(CRC)is a common cancer worldwide.Although there are several treatments for cancer,the therapeutic effect on CRC remains unsatisfactory,and it is imperative to identify new therapeutic targets.Design Prefoldin(PFDN)is mainly used in the cytoskeleton assembly during the folding of actin and tubulin monomers.However,whether PFDN subunits are involved in regulating the development of CRC remains to be elucidated.In this study,molecular biology,cell culture,transcriptome sequencing and other experimental techniques,combined with bioinformatics,were used to verify the regulatory effects of PFDN6 on CRC.Results PFDN6 expression is elevated in patients with CRC and is closely associated with the development of CRC.Knockdown of PFDN6 reduced the tumour cell number,promoted apoptosis,and inhibited the migration and invasion of CRC cells in HCT-116 and RKO cell lines.Mechanistically,differentially expressed genes and related signalling pathways in RKO cells after PFDN6 knockdown were analysed by transcriptome sequencing.Conclusion PFDN6 was found to regulate the generation and development of CRC by targeting ZNF575.These results open new avenues for therapeutic interventions for patients with CRC.展开更多
基金supported by the National Natural Science Foundation of China(Grant Numbers 82350117,82160476,32360046,82260462)First-Class Discipline Team of Kunming Medical University 2024XKTDYS07,Yunnan Provincial Department of Science and Technology Key Research and Development Plan for Social Development Special Projects(202403AC100022)+4 种基金The Fundamental Research Project of Yunnan Provincial Department of Science and Technology(202301AT070129)the Joint Special Funds for the Department of Science and Technology of Yunnan Province KunmingMedical University(Grant Number 202401AY070001-360)the Yunnan Provincial Department of Education Science Research Fund Project(Grant Number 2023Y0655,2024Y234)Yunnan Province Science and Technology Talents and Platform Plan Project(202305AF150067)Beijing Sci-Tech Innovation Medical Development Foundation KC2023-JX-0288-PM94.
文摘Background:Liver cancer stem cells(LCSCs)are recognized as pivotal drivers of hepatocellular carcinoma(HCC)progression;however,the molecular mechanisms maintaining their stem-like phenotype remain largely unresolved.This work investigates the role of prefoldin subunit 6-like protein(PFDN6L)in shaping LCSC traits and promoting or restraining HCC progression.Methods:PFDN6L,a cytoskeleton-associated chaperone,was studied using multiple in vitro assays—cell growth evaluation,cell cycle profiling,and spheroid culture—alongside analyses of stemness-associated markers(SOX2,CD133,CD44).Tumorigenic capacity was assessed in xenograft mouse models,and signaling pathway interrogation was performed to define underlying mechanisms.Results:In patient samples,higher PFDN6L expression correlated with improved survival outcomes.Forced expression of PFDN6L induced G2/M arrest,diminished sphere formation,and reduced pluripotency marker expression,whereas knockdown accelerated in vivo tumor formation.Mechanistic experiments demonstrated that PFDN6L suppressesmalignancy by simultaneously dampening AKT and ERK1/2 activation,thereby impairing oncogenic signaling cascades.Conclusion:PFDN6L acts as a negative regulator of LCSC-driven tumorigenesis.Its dual blockade of AKT and ERK pathways forms the mechanistic basis of its tumor-suppressive action,supporting its potential as a prognostic biomarker and therapeutic target in HCC.
基金supported by Doctoral‘Direct Access’Research Project of Chongqing(CSTB2022BSXM-JCX0012)the National Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0127)the 2023 programme for training talented pilots upon graduation(LHRCYB23009).
文摘Objective Colorectal cancer(CRC)is a common cancer worldwide.Although there are several treatments for cancer,the therapeutic effect on CRC remains unsatisfactory,and it is imperative to identify new therapeutic targets.Design Prefoldin(PFDN)is mainly used in the cytoskeleton assembly during the folding of actin and tubulin monomers.However,whether PFDN subunits are involved in regulating the development of CRC remains to be elucidated.In this study,molecular biology,cell culture,transcriptome sequencing and other experimental techniques,combined with bioinformatics,were used to verify the regulatory effects of PFDN6 on CRC.Results PFDN6 expression is elevated in patients with CRC and is closely associated with the development of CRC.Knockdown of PFDN6 reduced the tumour cell number,promoted apoptosis,and inhibited the migration and invasion of CRC cells in HCT-116 and RKO cell lines.Mechanistically,differentially expressed genes and related signalling pathways in RKO cells after PFDN6 knockdown were analysed by transcriptome sequencing.Conclusion PFDN6 was found to regulate the generation and development of CRC by targeting ZNF575.These results open new avenues for therapeutic interventions for patients with CRC.
