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
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.
