Objective:The dysregulation of ribosome biogenesis is associated with the progression of numerous tumors,including hepatocellular carcinoma(HCC).Small nucleolar RNAs(sno RNAs)regulate ribosome biogenesis by guiding th...Objective:The dysregulation of ribosome biogenesis is associated with the progression of numerous tumors,including hepatocellular carcinoma(HCC).Small nucleolar RNAs(sno RNAs)regulate ribosome biogenesis by guiding the modification of ribosomal RNAs(r RNAs).However,the underlying mechanism of this process in HCC remains elusive.Methods:RNA immunoprecipitation and sequencing were used to analyze RNAs targeted by ribosome proteins.The biological functions of SNORA23 were examined in HCC cells and a xenograft mouse model.To elucidate the underlying mechanisms,the 2′-O-ribose methylation level of r RNAs was evaluated by q PCR,and the key proteins in the PI3 K/Akt/m TOR pathway were detected using Western blot.Results:Twelve sno RNAs were found to co-exist in 4 cancer cell lines using RPS6 pull-down assays.SNORA23 was downregulated in HCC and correlated with the poor prognoses of HCC patients.SNORA23 inhibited the proliferation,migration,and invasion of HCC cells both in vitro and in vivo.We also found that SNORA23 regulated ribosome biogenesis by impairing 2′-O-ribose methylation of cytidine4506 of 28 S r RNA.Furthermore,SNORA23,which is regulated by the PI3 K/Akt/m TOR signaling pathway,significantly inhibited the phosphorylation of 4 E binding protein 1.SNORA23 and rapamycin blocked the PI3 K/AKT/m TOR signaling pathway and impaired HCC growth in vivo.Conclusions:SNORA23 exhibited antitumor effects in HCC and together with rapamycin,provided a promising therapeutic strategy for HCC treatment.展开更多
Rapid and reliable nucleic acid detection methods are essential in clinical diagnostics and biotechnology.The clustered regularly interspaced short palindromic repeats(CRISPR)system is emerging as a next-generation nu...Rapid and reliable nucleic acid detection methods are essential in clinical diagnostics and biotechnology.The clustered regularly interspaced short palindromic repeats(CRISPR)system is emerging as a next-generation nucleic acid detection technology,offering versatility,convenience and rapid detection.However,CRISPR methods are significantly limited by the protospacer adjacent motif(PAM)sequence,and achieving a one-pot reaction for detecting single nucleotide variations(SNVs)within a short time still remains challenging.Here,we developed a comprehensive method for screening PAM sequences,which significantly expands the CRISPR detection scope.Additionally,we also proposed a one-pot CRISPR method,termed"SIMPLE",capable of identifying SNVs within 30 min.We applied the SIMPLE method to the clinical diagnostics of drug-resistant bacteria and the screening of cancer hotspot mutations.The SIMPLE method successfully detected drug-resistant bacteria mediated by canonical PAM TTN sequence with a sensitivity of 10 copies per reaction and achieved 100%consistency with next-generation sequencing results.Furthermore,the SIMPLE method proved effective in detecting hotspot mutations in cancer,even at a low mutation rate of 1%in the presence of high background interference mediated by non-canonical PAM ATN sequence.Therefore,the SIMPLE method not only expands the CRISPR detection scope but also offers a one-pot reaction with high specificity for SNVs identification,making it a promising tool for next-generation molecular diagnostics.展开更多
Objective:This study aimed to assess the impact of proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitor treatment immediately after percutaneous coronary intervention(PCI)on the myocardial salvage index(MSI)i...Objective:This study aimed to assess the impact of proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitor treatment immediately after percutaneous coronary intervention(PCI)on the myocardial salvage index(MSI)in patients with anterior ST-segment elevation myocardial infarction(STEMI)5-10 d after the procedure.Methods:The early PCSK9 inhibitor thERapy Following pErcutaneous Coronary inTervention(PERFECT)trial is a prospective randomized controlled trial.From January 2021 to December 2023,32 patients with anterior STEMI from Tongren Hospital,Shanghai Jiao Tong University School of Medicine,Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,and Shanghai Tenth People’s Hospital were enrolled in the PERFECT trial.Patients were randomly assigned in a 1∶1 ratio to the PCSK9 inhibitor group(n=16)or the control group(n=16),and their baseline data were collected.Patients in the PCSK9 inhibitor group(ie,alirocumab group)received a subcutaneous injection of PCSK9 inhibitor(alirocumab,75 mg)immediately after PCI based on conventional treatment.In the control group,patients received only conventional treatment.The primary endpoint was the MSI measured by cardiovascular magnetic resonance 5-10 d after PCI.The secondary endpoints included the left ventricular ejection fraction measured by cardiovascular magnetic resonance 5-10 d after PCI and the time to peak of creatine kinase isoenzyme-MB and high-sensitivity cardiac troponin T.Safety endpoints included any clinical adverse events that occurred during the 6-month follow-up period.Results:Baseline data during admission showed no intergroup significance.No significant difference in MSI(55.54%±14.80%vs.44.72%±15.42%,P=0.056)and left ventricular ejection fraction(51.24%±8.91%vs.44.99%±8.84%,P=0.060)was observed.Additional,there was no significant difference in the time to peak of creatine kinase isoenzyme-MB((12.97±5.67)h vs.(14.31±7.04)h,P=0.557)and high-sensitivity cardiac troponin T((21.03±12.46)h vs.(21.44±9.99)h,P=0.920)between the 2 groups.During the 6-month follow-up period,only 1 patient in the PCSK9 inhibitor group developed cerebral hemorrhage 6 months after PCI.Conclusions:Early treatment with alirocumab did not exhibit a significant increase in MSI at 5-10 d in patients with anterior STEMI.Larger trials are necessary to evaluate the impact of early administration of PCSK9 inhibitors after myocardial infarction.展开更多
Background:Worldwide,the volume and availability of digestive endoscopy have undergone dramatic development in recent years,with increasing attention on quality assurance.We investigated the utilization and quality of...Background:Worldwide,the volume and availability of digestive endoscopy have undergone dramatic development in recent years,with increasing attention on quality assurance.We investigated the utilization and quality of digestive endoscopy in China from 2015 to 2019 and developed a quantitative quality evaluation tool for medical institutions.Methods:We invited all tertiary/secondary hospitals in Chinese mainland to participate in the survey annually.The questionnaires included the personnel,annual volume,and quality indicators of endoscopy.An endoscopy quality index(EQI)was developed based on recorded quality indicators using principal component analysis to determine the relative weight.Results:From 2015 to 2019,806,1412,2644,2468,and 2541 hospitals were respectively enrolled in this study.The average annual volume of endoscopy increased from 12,445 to 16,206(1.30-fold)and from 2938 to 4255(1.45-fold)in tertiary and secondary hospitals,respectively.The most obvious growth was observed in diagnostic colonoscopy(1.44-fold for all hospitals after standardization).The proportion of early cancer among all esophageal and gastric cancers during diagnostic esophagogastroduodenoscopy increased from 12.3%(55,210/448,861)to 17.7%(85,429/482,647)and from 11.4%(69,411/608,866)to 16.9%(107,192/634,235),respectively.The adenoma detection rate of diagnostic colonoscopy increased from 14.9%(2,118,123/14,215,592)to 19.3%(3,943,203/20,431,104).The EQI model included 12 quality indicators,incorporating 64.9%(7.792/12)of the total variance into one comprehensive index.According to the EQI measurements,the quality of endoscopy was higher in tertiary hospitals and hospitals in developed areas with higher volume or more endoscopists than that in other hospitals.Conclusions:Digestive endoscopy in China has developed considerably in recent years in terms of both volume and quality.The EQI is a promising tool to quantify the quality of endoscopy at different hospitals.展开更多
Objective: Emerging data have shown that non-coding RNAs (ncRNAs) can encode micro-peptides (≤100 amino acids) that play an important role in regulating physiological and pathological processes. Herein, we explored n...Objective: Emerging data have shown that non-coding RNAs (ncRNAs) can encode micro-peptides (≤100 amino acids) that play an important role in regulating physiological and pathological processes. Herein, we explored ncRNAs that may encode micro-peptides that are involved in the development of hepatocellular carcinoma (HCC).Methods: High-throughput sequencing of ribosomal protein S6 (RPS6) was performed in four cancer cell lines using RNA-immunoprecipitation (RIP). UCSC databases obtained the full length of the gene sequences and quantitative polymerase chain reaction (qPCR) was used to evaluate expression levels of ncRNAs of interest. The coding activity of ncRNA was assessedin vitro by co-immunoprecipitation, plasmid transfection, western blot, immunofluorescence and RNA fluorescencein situ hybridization. Mass spectrometry was performed to explore the potential functions of candidate micro-peptide in HCC. This study involving human tissue specimens was conducted in accordance withDeclaration of Helsinki and approved by the Institutional Review Board of Changhai Hospital, Naval Military Medical University, China (approval No. CHEC2020-081) on June 6, 2020.Results: We performed RIP assay using primary antibodies for RPS6 and high-throughput sequencing. A total of 223 overlapping genes were captured by RPS6-RIP. Venn diagram analysis revealed that 60 overlapping genes were detected in four cancer cell lines. QRT-PCR showed that six of the candidate genes (RP11-298J20.4, RP11-4O1.2, RP11-119F7.5, RP11-448G15.3, HCP5, RP11-517B11.7) were expressed in Huh7 and Hep3B cells. Further analysis of these six candidate genes and found that five (RP11-298J20.4, RP11-4O1.2, RP11-119F7.5, RP11-448G15.3, RP11-517B11.7) displayed higher expression levels in HCC cell lines (Huh7, Hep3B) and tumor tissues than in liver cell lines (L-02, QSG-7701) and non-tumor tissues, respectively. Performed additional RIP assays and confirmed that four of the genes (RP11-4O1.2, RP11-119F7.5, RP11-448G15.3, RP11-517B11 .7) bound RPS6. We obtained the full length of the four gene sequences from the UCSC database and analyzed the open reading frames by ORF Finder;to determine the translation potential of the four candidate small open reading frames (smORFs), we subcloned a FLAG epitope tag into the C-terminal of the four selected smORFs before the stop codon, and the fusion sequences were then cloned into three different plasmid vectors (pSPT19, pcDNA3.1, and PEGFP-N1). We performed coupled transcription and translation reactions and found that the pSPT19 plasmids encoded small peptidesin vitro. After then transfected the pcDNA3.1 constructs into Huh7 cells, and a single 7.2 kDa micro-peptide was encoded from the candidate smORF of RP11.119F7.5. We transfected the recombinant pEGFP-N1 plasmids with smORFs in HCC cells, and western blot analysis revealed a band above GFP in the RP11.119F7.5 recombinant plasmid lane. The coding potential of the RP11-119F7.5 vector was also confirmed by immunofluorescence assay. Fluorescencein situ hybridization assay revealed that RP11-119F7.5 was localized in the cytoplasm and nucleoplasm of HCC cells. Gene ontology enrichment analysis showed that the micro-peptide–interacting proteins were mainly involved in extracellular exosomes. We also found the identified proteins were involved in several biological functions like protein binding, poly(A) RNA binding, translational initiation, and the nuclear-transcribed mRNA catabolic process. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed the peptide-interacting proteins might participate in several critical pathways including ribosome, biosynthesis of amino acids, carbon metabolism, biosynthesis of antibiotics, glycolysis and gluconeogenesis, pathogenicEscherichia coli infection and influenza A.Conclusion: Our study revealed a novel micro-peptide translated by ncRNA RP11-119F7.5, highlighting the coding ability and potential role of ncRNAs in HCC.展开更多
Dysregulated RNA splicing events produce transcripts that facilitate esophageal squamous cell carcinoma(ESCC)progression,but how this splicing process is abnormally regulated remains elusive.Here,we unveiled a novel a...Dysregulated RNA splicing events produce transcripts that facilitate esophageal squamous cell carcinoma(ESCC)progression,but how this splicing process is abnormally regulated remains elusive.Here,we unveiled a novel alternative splicing axis of BOLA3 transcripts and its regulator HNRNPC in ESCC.The long-form BOLA3(BOLA3-L)containing exon 3 exhibited high expression levels in ESCC and was associated with poor prognosis.Functional assays demonstrated the protumorigenic function of BOLA3-L in ESCC cells.Additionally,HNRNPC bound to BOLA3 mRNA and promoted BOLA3 exon 3 inclusion forming BOLA3-L.High HNRNPC expression was positively correlated with the presence of BOLA3-L and associated with an unfavorable prognosis.HNRNPC knockdown effectively suppressed the malignant biological behavior of ESCC cells,which were significantly rescued by BOLA3-L overexpression.Moreover,BOLA3-L played a significant role in mitochondrial structural and functional stability.E2F7 acted as a key transcription factor that promoted the upregulation of HNRNPC and inclusion of BOLA3 exon 3.Our findings provided novel insights into how alternative splicing contributes to ESCC progression.展开更多
基金supported by the China National Funds for Distinguished Young Scientists(Grant No.81425019)the Shanghai Science and Technology Committee Program(Grant No.18XD1405300)the National Natural Science Foundation of China(Grant No.32001786)。
文摘Objective:The dysregulation of ribosome biogenesis is associated with the progression of numerous tumors,including hepatocellular carcinoma(HCC).Small nucleolar RNAs(sno RNAs)regulate ribosome biogenesis by guiding the modification of ribosomal RNAs(r RNAs).However,the underlying mechanism of this process in HCC remains elusive.Methods:RNA immunoprecipitation and sequencing were used to analyze RNAs targeted by ribosome proteins.The biological functions of SNORA23 were examined in HCC cells and a xenograft mouse model.To elucidate the underlying mechanisms,the 2′-O-ribose methylation level of r RNAs was evaluated by q PCR,and the key proteins in the PI3 K/Akt/m TOR pathway were detected using Western blot.Results:Twelve sno RNAs were found to co-exist in 4 cancer cell lines using RPS6 pull-down assays.SNORA23 was downregulated in HCC and correlated with the poor prognoses of HCC patients.SNORA23 inhibited the proliferation,migration,and invasion of HCC cells both in vitro and in vivo.We also found that SNORA23 regulated ribosome biogenesis by impairing 2′-O-ribose methylation of cytidine4506 of 28 S r RNA.Furthermore,SNORA23,which is regulated by the PI3 K/Akt/m TOR signaling pathway,significantly inhibited the phosphorylation of 4 E binding protein 1.SNORA23 and rapamycin blocked the PI3 K/AKT/m TOR signaling pathway and impaired HCC growth in vivo.Conclusions:SNORA23 exhibited antitumor effects in HCC and together with rapamycin,provided a promising therapeutic strategy for HCC treatment.
基金supported by the National Natural Science Foundation of China(32371521,82300220)Special Project for Experimental Animal Research(23141900300)+3 种基金Shanghai Rising Star Program(23QA1404300)Special Project for Medical Innovation Research(22Y11909200)Greater Bay Area Institute of Precision Medicine(Guangzhou)Human Phenome Data Center of Fudan University and Shanghai Municipal Science and Technology Major Project.(2023SHZDZX02).
文摘Rapid and reliable nucleic acid detection methods are essential in clinical diagnostics and biotechnology.The clustered regularly interspaced short palindromic repeats(CRISPR)system is emerging as a next-generation nucleic acid detection technology,offering versatility,convenience and rapid detection.However,CRISPR methods are significantly limited by the protospacer adjacent motif(PAM)sequence,and achieving a one-pot reaction for detecting single nucleotide variations(SNVs)within a short time still remains challenging.Here,we developed a comprehensive method for screening PAM sequences,which significantly expands the CRISPR detection scope.Additionally,we also proposed a one-pot CRISPR method,termed"SIMPLE",capable of identifying SNVs within 30 min.We applied the SIMPLE method to the clinical diagnostics of drug-resistant bacteria and the screening of cancer hotspot mutations.The SIMPLE method successfully detected drug-resistant bacteria mediated by canonical PAM TTN sequence with a sensitivity of 10 copies per reaction and achieved 100%consistency with next-generation sequencing results.Furthermore,the SIMPLE method proved effective in detecting hotspot mutations in cancer,even at a low mutation rate of 1%in the presence of high background interference mediated by non-canonical PAM ATN sequence.Therefore,the SIMPLE method not only expands the CRISPR detection scope but also offers a one-pot reaction with high specificity for SNVs identification,making it a promising tool for next-generation molecular diagnostics.
基金supported by the National Natural Science Foundation of China(82270276)the Xinxin Heart Foundation from China Cardiovascular Association(2021-CCA-ACCESS-73).
文摘Objective:This study aimed to assess the impact of proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitor treatment immediately after percutaneous coronary intervention(PCI)on the myocardial salvage index(MSI)in patients with anterior ST-segment elevation myocardial infarction(STEMI)5-10 d after the procedure.Methods:The early PCSK9 inhibitor thERapy Following pErcutaneous Coronary inTervention(PERFECT)trial is a prospective randomized controlled trial.From January 2021 to December 2023,32 patients with anterior STEMI from Tongren Hospital,Shanghai Jiao Tong University School of Medicine,Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,and Shanghai Tenth People’s Hospital were enrolled in the PERFECT trial.Patients were randomly assigned in a 1∶1 ratio to the PCSK9 inhibitor group(n=16)or the control group(n=16),and their baseline data were collected.Patients in the PCSK9 inhibitor group(ie,alirocumab group)received a subcutaneous injection of PCSK9 inhibitor(alirocumab,75 mg)immediately after PCI based on conventional treatment.In the control group,patients received only conventional treatment.The primary endpoint was the MSI measured by cardiovascular magnetic resonance 5-10 d after PCI.The secondary endpoints included the left ventricular ejection fraction measured by cardiovascular magnetic resonance 5-10 d after PCI and the time to peak of creatine kinase isoenzyme-MB and high-sensitivity cardiac troponin T.Safety endpoints included any clinical adverse events that occurred during the 6-month follow-up period.Results:Baseline data during admission showed no intergroup significance.No significant difference in MSI(55.54%±14.80%vs.44.72%±15.42%,P=0.056)and left ventricular ejection fraction(51.24%±8.91%vs.44.99%±8.84%,P=0.060)was observed.Additional,there was no significant difference in the time to peak of creatine kinase isoenzyme-MB((12.97±5.67)h vs.(14.31±7.04)h,P=0.557)and high-sensitivity cardiac troponin T((21.03±12.46)h vs.(21.44±9.99)h,P=0.920)between the 2 groups.During the 6-month follow-up period,only 1 patient in the PCSK9 inhibitor group developed cerebral hemorrhage 6 months after PCI.Conclusions:Early treatment with alirocumab did not exhibit a significant increase in MSI at 5-10 d in patients with anterior STEMI.Larger trials are necessary to evaluate the impact of early administration of PCSK9 inhibitors after myocardial infarction.
基金supported by the National Health Commission of China, First Affiliated Hospital of Naval Medical University(No. 2019YXK006)the Science and Technology Commission of Shanghai Municipality(No. 21Y31900100)
文摘Background:Worldwide,the volume and availability of digestive endoscopy have undergone dramatic development in recent years,with increasing attention on quality assurance.We investigated the utilization and quality of digestive endoscopy in China from 2015 to 2019 and developed a quantitative quality evaluation tool for medical institutions.Methods:We invited all tertiary/secondary hospitals in Chinese mainland to participate in the survey annually.The questionnaires included the personnel,annual volume,and quality indicators of endoscopy.An endoscopy quality index(EQI)was developed based on recorded quality indicators using principal component analysis to determine the relative weight.Results:From 2015 to 2019,806,1412,2644,2468,and 2541 hospitals were respectively enrolled in this study.The average annual volume of endoscopy increased from 12,445 to 16,206(1.30-fold)and from 2938 to 4255(1.45-fold)in tertiary and secondary hospitals,respectively.The most obvious growth was observed in diagnostic colonoscopy(1.44-fold for all hospitals after standardization).The proportion of early cancer among all esophageal and gastric cancers during diagnostic esophagogastroduodenoscopy increased from 12.3%(55,210/448,861)to 17.7%(85,429/482,647)and from 11.4%(69,411/608,866)to 16.9%(107,192/634,235),respectively.The adenoma detection rate of diagnostic colonoscopy increased from 14.9%(2,118,123/14,215,592)to 19.3%(3,943,203/20,431,104).The EQI model included 12 quality indicators,incorporating 64.9%(7.792/12)of the total variance into one comprehensive index.According to the EQI measurements,the quality of endoscopy was higher in tertiary hospitals and hospitals in developed areas with higher volume or more endoscopists than that in other hospitals.Conclusions:Digestive endoscopy in China has developed considerably in recent years in terms of both volume and quality.The EQI is a promising tool to quantify the quality of endoscopy at different hospitals.
基金Key Program of National Natural Science Foundation of China(No.82030073).
文摘Objective: Emerging data have shown that non-coding RNAs (ncRNAs) can encode micro-peptides (≤100 amino acids) that play an important role in regulating physiological and pathological processes. Herein, we explored ncRNAs that may encode micro-peptides that are involved in the development of hepatocellular carcinoma (HCC).Methods: High-throughput sequencing of ribosomal protein S6 (RPS6) was performed in four cancer cell lines using RNA-immunoprecipitation (RIP). UCSC databases obtained the full length of the gene sequences and quantitative polymerase chain reaction (qPCR) was used to evaluate expression levels of ncRNAs of interest. The coding activity of ncRNA was assessedin vitro by co-immunoprecipitation, plasmid transfection, western blot, immunofluorescence and RNA fluorescencein situ hybridization. Mass spectrometry was performed to explore the potential functions of candidate micro-peptide in HCC. This study involving human tissue specimens was conducted in accordance withDeclaration of Helsinki and approved by the Institutional Review Board of Changhai Hospital, Naval Military Medical University, China (approval No. CHEC2020-081) on June 6, 2020.Results: We performed RIP assay using primary antibodies for RPS6 and high-throughput sequencing. A total of 223 overlapping genes were captured by RPS6-RIP. Venn diagram analysis revealed that 60 overlapping genes were detected in four cancer cell lines. QRT-PCR showed that six of the candidate genes (RP11-298J20.4, RP11-4O1.2, RP11-119F7.5, RP11-448G15.3, HCP5, RP11-517B11.7) were expressed in Huh7 and Hep3B cells. Further analysis of these six candidate genes and found that five (RP11-298J20.4, RP11-4O1.2, RP11-119F7.5, RP11-448G15.3, RP11-517B11.7) displayed higher expression levels in HCC cell lines (Huh7, Hep3B) and tumor tissues than in liver cell lines (L-02, QSG-7701) and non-tumor tissues, respectively. Performed additional RIP assays and confirmed that four of the genes (RP11-4O1.2, RP11-119F7.5, RP11-448G15.3, RP11-517B11 .7) bound RPS6. We obtained the full length of the four gene sequences from the UCSC database and analyzed the open reading frames by ORF Finder;to determine the translation potential of the four candidate small open reading frames (smORFs), we subcloned a FLAG epitope tag into the C-terminal of the four selected smORFs before the stop codon, and the fusion sequences were then cloned into three different plasmid vectors (pSPT19, pcDNA3.1, and PEGFP-N1). We performed coupled transcription and translation reactions and found that the pSPT19 plasmids encoded small peptidesin vitro. After then transfected the pcDNA3.1 constructs into Huh7 cells, and a single 7.2 kDa micro-peptide was encoded from the candidate smORF of RP11.119F7.5. We transfected the recombinant pEGFP-N1 plasmids with smORFs in HCC cells, and western blot analysis revealed a band above GFP in the RP11.119F7.5 recombinant plasmid lane. The coding potential of the RP11-119F7.5 vector was also confirmed by immunofluorescence assay. Fluorescencein situ hybridization assay revealed that RP11-119F7.5 was localized in the cytoplasm and nucleoplasm of HCC cells. Gene ontology enrichment analysis showed that the micro-peptide–interacting proteins were mainly involved in extracellular exosomes. We also found the identified proteins were involved in several biological functions like protein binding, poly(A) RNA binding, translational initiation, and the nuclear-transcribed mRNA catabolic process. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed the peptide-interacting proteins might participate in several critical pathways including ribosome, biosynthesis of amino acids, carbon metabolism, biosynthesis of antibiotics, glycolysis and gluconeogenesis, pathogenicEscherichia coli infection and influenza A.Conclusion: Our study revealed a novel micro-peptide translated by ncRNA RP11-119F7.5, highlighting the coding ability and potential role of ncRNAs in HCC.
基金supported by Shanghai Science and Technology Innovation Action Program(No.21Y31900100).
文摘Dysregulated RNA splicing events produce transcripts that facilitate esophageal squamous cell carcinoma(ESCC)progression,but how this splicing process is abnormally regulated remains elusive.Here,we unveiled a novel alternative splicing axis of BOLA3 transcripts and its regulator HNRNPC in ESCC.The long-form BOLA3(BOLA3-L)containing exon 3 exhibited high expression levels in ESCC and was associated with poor prognosis.Functional assays demonstrated the protumorigenic function of BOLA3-L in ESCC cells.Additionally,HNRNPC bound to BOLA3 mRNA and promoted BOLA3 exon 3 inclusion forming BOLA3-L.High HNRNPC expression was positively correlated with the presence of BOLA3-L and associated with an unfavorable prognosis.HNRNPC knockdown effectively suppressed the malignant biological behavior of ESCC cells,which were significantly rescued by BOLA3-L overexpression.Moreover,BOLA3-L played a significant role in mitochondrial structural and functional stability.E2F7 acted as a key transcription factor that promoted the upregulation of HNRNPC and inclusion of BOLA3 exon 3.Our findings provided novel insights into how alternative splicing contributes to ESCC progression.
