Objective:Increasing evidence has demonstrated that ZNF292 plays a suppressive role in cancer,however,little is known about its function and exact mechanism in esophageal squamous cell carcinoma(ESCC).Methods:Bioinfor...Objective:Increasing evidence has demonstrated that ZNF292 plays a suppressive role in cancer,however,little is known about its function and exact mechanism in esophageal squamous cell carcinoma(ESCC).Methods:Bioinformatic analysis and immunohistochemistry(IHC)were performed to analyze the role of ZNF292 in affecting the prognosis of ESCC.Cell proliferation and colony formation ability assays were performed to analyze cell growth after inferring the expression of ZNF292.Flow cytometry was used to analyze changes in the cell cycle upon the depletion of ZNF292.Quantitative real-time polymerase chain reaction(q RT-PCR)and western blot analysis were used to determine the alteration of cell cycle related RNAs and proteins after knocking down ZNF292.MG-132,cycloheximide(CHX)treatment experiments were performed to analyze the change and half-life time of P27 after knockdown of ZNF292.Chromatin immunoprecipitation(Ch IP)and luciferase reporter assays were used to analyze the transcriptional regulation of SKP2 by ZNF292.Results:We report that low expression of ZNF292 is associated with poor prognosis,and ZNF292 emerges to be highly expressed in adjacent and normal tissues rather than tumor tissues in ESCC.Knockdown of ZNF292 significantly boosts cell growth and S phase entry in ESCC cells.ZNF292 depletion will decrease the expression and half-life time of P27,while knockdown of SKP2 will result in elevated expression of P27.ZNF292 can bind to the promoter region of SKP2,and knockdown of ZNF292 will boost the expression of SKP2.Conclusions:Knockdown of ZNF292 mediates G1/S cell cycle procession by activating SKP2/P27 signaling in ESCC cells.ZNF292 knockdown promotes SKP2 expression at the transcriptional level,thereby boosting P27 ubiquitin-degradation,and eventually facilitating the S phase entrance.展开更多
Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squ...Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squamous cell carcinoma(ESCC) remains elusive.This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.Methods:ESCC cell lines treated with or without melatonin were used in this study.In vitro colony formation and 5-Ethynyl-2’-deoxyuridine(EdU) incorporation assays,and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells.RNA-seq,qPCR,Western blotting,recombinant lentivirus-mediated target gene overexpression or knockdown,plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth.IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes’ expression and prognosis of ESCC.Results:Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7(HDAC7),c-Myc and ubiquitin-specific peptidase 10(USP10) in ESCC cells(P<0.05).The expressions of HDAC7,c-Myc and USP10 in tumors were significantly higher than the paired normal tissues from 148 ESCC patients(P<0.001).Then,the Kaplan-Meier survival analysis suggested that ESCC patients with high HDAC7,c-Myc or USP10levels predicted worse overall survival(log-rank P<0.001).Co-IP and Western blotting further revealed that HDAC7physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription.Notably,our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth,and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells.Additionally,we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.Conclusions:Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth,and provides the reference for identifying biomarkers and therapeutic targets for ESCC.展开更多
Objective： The aim of the study was to investigate the association of esophageal squamous cell carcinoma （ESCC） genetic susceptibility with the single nucleotide polymorphism （SNP） rs679620 （-Lys45Glu-） in exon...Objective： The aim of the study was to investigate the association of esophageal squamous cell carcinoma （ESCC） genetic susceptibility with the single nucleotide polymorphism （SNP） rs679620 （-Lys45Glu-） in exon 2 of the romp3 gene, and the population in high incidence region of Henan （China） was selected for exploring the mechanism by case-control study, Methods： The romp3 SNP was genotyped by PCR-RFLP analysis in total 605 cases of Henan population, in which there were 227 ESCC cases and 197 controls of An-yang in Henan plus 181 controls of emigrants in Hubei from Xi-chuan of Henan, China. Results： The statistic data showed that GIG and G/A genotype frequencies of SNP rs679620 were significantly different between the controls of emigrants of Xi-chuan in Hubei and controls of An-yang in Henan （P 〈 0.01） also the ESCC cases of An-yang in Henan （P 〈 0.01）, respectively. Conclusion： This study suggests that the SNP rs679620 （-Lys45Glu-） in exon 2 of the mmp3 gene might be associated with ESCC genetic susceptibility.展开更多
Objective To determine HPV infection status and expression of p16, cyclooxygenase-2(COX-2), Cyclin D1 and epidermal growth factor receptor(EGFR) in ESCC patients of Pakistan. Methods 51 ESCC patients treated at Aga Kh...Objective To determine HPV infection status and expression of p16, cyclooxygenase-2(COX-2), Cyclin D1 and epidermal growth factor receptor(EGFR) in ESCC patients of Pakistan. Methods 51 ESCC patients treated at Aga Khan University Hospital(AKUH) were included. HPV infection status was confirmed via PCR while the expression of the four biomarkers was determined using immunohistochemistry. The correlation of all markers with patient clinicopathological features as well as each other was analyzed. Results HPV infection status and p16 overexpression was found to be negative in all the patients while COX-2, Cyclin D1 and EGFR were overexpressed in 56.9%, 62.7% and 49.0% of the patients respectively. COX-2 showed a significant correlation with tumor invasion while EGFR was shown to be significantly correlated with histological grading and COX-2 expression. Conclusion COX-2 and EGFR can be used as prognostic markers. HPV does not seem to be a causative agent for ESCC in Pakistan.展开更多
Cellular senescence provides a protective barrier against tumorigenesis in precancerous or normal tissues upon distinct stressors.However,the detailed mechanisms by which tumor cells evade premature senescence to mali...Cellular senescence provides a protective barrier against tumorigenesis in precancerous or normal tissues upon distinct stressors.However,the detailed mechanisms by which tumor cells evade premature senescence to malignant progression remain largely elusive.Here we reported that RBM4 adversely impacted cellular senescence to favor glutamine-dependent survival of esophageal squamous cell carcinoma(ESCC)cells by dictating the activity of LKB1,a critical governor of cancer metabolism.The level of RBM4 was specifically elevated in ESCC compared to normal tissues,and RBM4 overexpression promoted the malignant phenotype.RBM4 contributed to overcome H-RAS-or doxorubicin-induced senescence,while its depletion caused P27-dependent senescence and proliferation arrest by activating LKB1-AMPK-mTOR cascade.Mechanistically,RBM4 competitively bound LKB1 to disrupt the LKB1/STRAD/MO25 heterotrimeric complex,subsequently recruiting the E3 ligase TRIM26 to LKB1,promoting LKB1 ubiquitination and degradation in nucleus.Therefore,such molecular process leads to bypassing senescence and sustaining cell proliferation through the activation of glutamine metabolism.Clinically,the ESCC patients with high RBM4 and low LKB1 have significantly worse overall survival than those with low RBM4 and high LKB1.The RBM4 high/LKB1 low expression confers increased sensitivity of ESCC cells to glutaminase inhibitor CB-839,providing a novel insight into mechanisms underlying the glutamine-dependency to improve the efficacy of glutamine inhibitors in ESCC therapeutics.展开更多
Pristimerin,which is one of the compounds present in Celastraceae and Hippocrateaceae,has antitumor effects.However,its mechanism of action in esophageal squamous cell carcinoma(ESCC)remains unclear.This study aims to...Pristimerin,which is one of the compounds present in Celastraceae and Hippocrateaceae,has antitumor effects.However,its mechanism of action in esophageal squamous cell carcinoma(ESCC)remains unclear.This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo.The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays.Cell apoptosis was evaluated by flow cytometry.Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry.RNA sequencing(RNA-Seq)was employed to identify significantly differentially expressed genes(DEGs).Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin's effect.Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo.Pristimerin inhibited cell growth and induced apoptosis in ESCC cells.Upregulation of Noxa was crucial for pristimerin-induced apoptosis.Pristimerin activated the Forkhead box O3a(FoxO3a)signaling pathway and triggered FoxO3a recruitment to the Noxa promoter,leading to Noxa transcription.Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis.Pristimerin treatment suppressed xenograft tumors in nude mice,but these effects were largely negated in Noxa-KO tumors.Furthermore,the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa.This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation.These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.展开更多
Objectives:Epigenetic changes,particularly N6-methyladenosine(m6A)modifications,play a pivotal role in cancer development.This study explored the role of ovarian tumor deubiquitinase 7B(OTUD7B)in esophageal squamous c...Objectives:Epigenetic changes,particularly N6-methyladenosine(m6A)modifications,play a pivotal role in cancer development.This study explored the role of ovarian tumor deubiquitinase 7B(OTUD7B)in esophageal squamous cell carcinoma(ESCC)in the context of m6A methylation and the hypoxia-inducible factor-1α(HIF-1α)pathway.Methods:The GSE179267 dataset was used to conduct differential gene expression analysis to identify key m6A-enriched genes.The Cancer Genome Atlas(TCGA),Cancer Cell Line Encyclopedia(CCLE),and Sequence-based RNA Adenosine Methylation Site Predictor(SRAMP)databases were used to evaluate the expression of OTUD7B in ESCC and its correlation with methyltransferase-like 14(METTL14)and HIF-1α.The m6A content in total RNA extracted from ESCC cells was assessed using a dot blot assay.Gene-specific m6A-PCR was used to quantify m6A modifications in OTUD7B mRNA.The functional role of OTUD7B was explored using clonogenic and Transwell assays.The effect of OTUD7B on HIF-1αubiquitination was detected using a co-immunoprecipitation assay.Results:OTUD7B was identified as a pivotal m6A-driven oncogene correlated with METTL14 and HIF-1α.METTL14 enhanced the mRNA stability and expression of OTUD7B through m6A methylation.OTUD7B overexpression counteracted the inhibitory effects of METTL14 knockdown on cell proliferation and invasion and stabilized HIF-1αby promoting deubiquitination.Conclusion:METTL14 plays a crucial role in the stabilization of OTUD7B through m6A methylation,thereby inhibiting the ubiquitin-proteasomal degradation of HIF-1αin ESCC.These findings highlight the potential of targeting the METTL14-OTUD7B axis as a therapeutic strategy for ESCC.展开更多
基金supported by the National Natural Fund of China(No.81988101,81830086 and 81972318)the Doctoral Innovation Fund of Peking Union Medical College(No.2018071011)。
文摘Objective:Increasing evidence has demonstrated that ZNF292 plays a suppressive role in cancer,however,little is known about its function and exact mechanism in esophageal squamous cell carcinoma(ESCC).Methods:Bioinformatic analysis and immunohistochemistry(IHC)were performed to analyze the role of ZNF292 in affecting the prognosis of ESCC.Cell proliferation and colony formation ability assays were performed to analyze cell growth after inferring the expression of ZNF292.Flow cytometry was used to analyze changes in the cell cycle upon the depletion of ZNF292.Quantitative real-time polymerase chain reaction(q RT-PCR)and western blot analysis were used to determine the alteration of cell cycle related RNAs and proteins after knocking down ZNF292.MG-132,cycloheximide(CHX)treatment experiments were performed to analyze the change and half-life time of P27 after knockdown of ZNF292.Chromatin immunoprecipitation(Ch IP)and luciferase reporter assays were used to analyze the transcriptional regulation of SKP2 by ZNF292.Results:We report that low expression of ZNF292 is associated with poor prognosis,and ZNF292 emerges to be highly expressed in adjacent and normal tissues rather than tumor tissues in ESCC.Knockdown of ZNF292 significantly boosts cell growth and S phase entry in ESCC cells.ZNF292 depletion will decrease the expression and half-life time of P27,while knockdown of SKP2 will result in elevated expression of P27.ZNF292 can bind to the promoter region of SKP2,and knockdown of ZNF292 will boost the expression of SKP2.Conclusions:Knockdown of ZNF292 mediates G1/S cell cycle procession by activating SKP2/P27 signaling in ESCC cells.ZNF292 knockdown promotes SKP2 expression at the transcriptional level,thereby boosting P27 ubiquitin-degradation,and eventually facilitating the S phase entrance.
基金supported by the National Natural Science Foundation of China (82103508, 81871866, 82173252, 81672996)the Natural Science Foundation of Shaanxi Province (2022JQ?862)。
文摘Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squamous cell carcinoma(ESCC) remains elusive.This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.Methods:ESCC cell lines treated with or without melatonin were used in this study.In vitro colony formation and 5-Ethynyl-2’-deoxyuridine(EdU) incorporation assays,and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells.RNA-seq,qPCR,Western blotting,recombinant lentivirus-mediated target gene overexpression or knockdown,plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth.IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes’ expression and prognosis of ESCC.Results:Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7(HDAC7),c-Myc and ubiquitin-specific peptidase 10(USP10) in ESCC cells(P<0.05).The expressions of HDAC7,c-Myc and USP10 in tumors were significantly higher than the paired normal tissues from 148 ESCC patients(P<0.001).Then,the Kaplan-Meier survival analysis suggested that ESCC patients with high HDAC7,c-Myc or USP10levels predicted worse overall survival(log-rank P<0.001).Co-IP and Western blotting further revealed that HDAC7physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription.Notably,our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth,and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells.Additionally,we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.Conclusions:Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth,and provides the reference for identifying biomarkers and therapeutic targets for ESCC.
基金Supported by a grant from the Natural Sciences Foundation of State Ethnic Affairs Commission of China (No. 07ZN09)
文摘Objective： The aim of the study was to investigate the association of esophageal squamous cell carcinoma （ESCC） genetic susceptibility with the single nucleotide polymorphism （SNP） rs679620 （-Lys45Glu-） in exon 2 of the romp3 gene, and the population in high incidence region of Henan （China） was selected for exploring the mechanism by case-control study, Methods： The romp3 SNP was genotyped by PCR-RFLP analysis in total 605 cases of Henan population, in which there were 227 ESCC cases and 197 controls of An-yang in Henan plus 181 controls of emigrants in Hubei from Xi-chuan of Henan, China. Results： The statistic data showed that GIG and G/A genotype frequencies of SNP rs679620 were significantly different between the controls of emigrants of Xi-chuan in Hubei and controls of An-yang in Henan （P 〈 0.01） also the ESCC cases of An-yang in Henan （P 〈 0.01）, respectively. Conclusion： This study suggests that the SNP rs679620 （-Lys45Glu-） in exon 2 of the mmp3 gene might be associated with ESCC genetic susceptibility.
基金supported by Seed Money Grant,Aga Khan University Hospital,awarded to Dr.Syed Muhammad Adnan Ali.Grant ID:80095
文摘Objective To determine HPV infection status and expression of p16, cyclooxygenase-2(COX-2), Cyclin D1 and epidermal growth factor receptor(EGFR) in ESCC patients of Pakistan. Methods 51 ESCC patients treated at Aga Khan University Hospital(AKUH) were included. HPV infection status was confirmed via PCR while the expression of the four biomarkers was determined using immunohistochemistry. The correlation of all markers with patient clinicopathological features as well as each other was analyzed. Results HPV infection status and p16 overexpression was found to be negative in all the patients while COX-2, Cyclin D1 and EGFR were overexpressed in 56.9%, 62.7% and 49.0% of the patients respectively. COX-2 showed a significant correlation with tumor invasion while EGFR was shown to be significantly correlated with histological grading and COX-2 expression. Conclusion COX-2 and EGFR can be used as prognostic markers. HPV does not seem to be a causative agent for ESCC in Pakistan.
基金supported by the National Natural Science Foundation of China (82225034,81830088 to Y.W.,82103148 to Y.Q.81872247 to W.Z.)+4 种基金the Department of Science and Technology of Liaoning Province (2021JH6/10500160 to Y.W.)the Basic Scientific Research Project of Education Department of Liaoning Province (LJKQZ2021104 to Y.Q.)the Science and Technology Innovation Talent Support Program of Dalian (2022RQ056 Y.Q.)the Science and Technology Innovation Foundation of Dalian (2022JJ11CG009 to Y.W.)Dalian High Level Talents Renovation Supporting Program (2019RQ097 to W.Z.).
文摘Cellular senescence provides a protective barrier against tumorigenesis in precancerous or normal tissues upon distinct stressors.However,the detailed mechanisms by which tumor cells evade premature senescence to malignant progression remain largely elusive.Here we reported that RBM4 adversely impacted cellular senescence to favor glutamine-dependent survival of esophageal squamous cell carcinoma(ESCC)cells by dictating the activity of LKB1,a critical governor of cancer metabolism.The level of RBM4 was specifically elevated in ESCC compared to normal tissues,and RBM4 overexpression promoted the malignant phenotype.RBM4 contributed to overcome H-RAS-or doxorubicin-induced senescence,while its depletion caused P27-dependent senescence and proliferation arrest by activating LKB1-AMPK-mTOR cascade.Mechanistically,RBM4 competitively bound LKB1 to disrupt the LKB1/STRAD/MO25 heterotrimeric complex,subsequently recruiting the E3 ligase TRIM26 to LKB1,promoting LKB1 ubiquitination and degradation in nucleus.Therefore,such molecular process leads to bypassing senescence and sustaining cell proliferation through the activation of glutamine metabolism.Clinically,the ESCC patients with high RBM4 and low LKB1 have significantly worse overall survival than those with low RBM4 and high LKB1.The RBM4 high/LKB1 low expression confers increased sensitivity of ESCC cells to glutaminase inhibitor CB-839,providing a novel insight into mechanisms underlying the glutamine-dependency to improve the efficacy of glutamine inhibitors in ESCC therapeutics.
基金supported by the Projects of International Cooperation and Exchanges(Nos.G2022027004L,G2022027012L)the Hubei Province Natural Science Foundation of China(No.2022CFB481)+3 种基金the Natural Science Foundation of Hubei Provincial Department of Education(No.T2022021)the Advantages Discipline Group(Biology and Medicine)Project in Higher Education of Hubei Province(2021-2025)(Nos.2025BMXKQY2,2024XKQY26)the Innovative Research Program for Graduates of Hubei University of Medicine(No.YC2024003,YC2022033)the Student's Platform for Innovation and Entrepreneurship Training Program(Nos.202410929010,202210929005)。
文摘Pristimerin,which is one of the compounds present in Celastraceae and Hippocrateaceae,has antitumor effects.However,its mechanism of action in esophageal squamous cell carcinoma(ESCC)remains unclear.This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo.The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays.Cell apoptosis was evaluated by flow cytometry.Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry.RNA sequencing(RNA-Seq)was employed to identify significantly differentially expressed genes(DEGs).Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin's effect.Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo.Pristimerin inhibited cell growth and induced apoptosis in ESCC cells.Upregulation of Noxa was crucial for pristimerin-induced apoptosis.Pristimerin activated the Forkhead box O3a(FoxO3a)signaling pathway and triggered FoxO3a recruitment to the Noxa promoter,leading to Noxa transcription.Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis.Pristimerin treatment suppressed xenograft tumors in nude mice,but these effects were largely negated in Noxa-KO tumors.Furthermore,the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa.This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation.These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
基金funded by the Doctoral Research Start-up Fund Project at Changzhi Medical College(grant number BS202118)Sichuan Science and Technology Program(grant number 2022YFS0631)Scientific and Technological Innovation Programs ofHigher Education Institutions in Shanxi(grant number 2021L348).
文摘Objectives:Epigenetic changes,particularly N6-methyladenosine(m6A)modifications,play a pivotal role in cancer development.This study explored the role of ovarian tumor deubiquitinase 7B(OTUD7B)in esophageal squamous cell carcinoma(ESCC)in the context of m6A methylation and the hypoxia-inducible factor-1α(HIF-1α)pathway.Methods:The GSE179267 dataset was used to conduct differential gene expression analysis to identify key m6A-enriched genes.The Cancer Genome Atlas(TCGA),Cancer Cell Line Encyclopedia(CCLE),and Sequence-based RNA Adenosine Methylation Site Predictor(SRAMP)databases were used to evaluate the expression of OTUD7B in ESCC and its correlation with methyltransferase-like 14(METTL14)and HIF-1α.The m6A content in total RNA extracted from ESCC cells was assessed using a dot blot assay.Gene-specific m6A-PCR was used to quantify m6A modifications in OTUD7B mRNA.The functional role of OTUD7B was explored using clonogenic and Transwell assays.The effect of OTUD7B on HIF-1αubiquitination was detected using a co-immunoprecipitation assay.Results:OTUD7B was identified as a pivotal m6A-driven oncogene correlated with METTL14 and HIF-1α.METTL14 enhanced the mRNA stability and expression of OTUD7B through m6A methylation.OTUD7B overexpression counteracted the inhibitory effects of METTL14 knockdown on cell proliferation and invasion and stabilized HIF-1αby promoting deubiquitination.Conclusion:METTL14 plays a crucial role in the stabilization of OTUD7B through m6A methylation,thereby inhibiting the ubiquitin-proteasomal degradation of HIF-1αin ESCC.These findings highlight the potential of targeting the METTL14-OTUD7B axis as a therapeutic strategy for ESCC.
