Between 1981 and 1988, 234 cases of cancerof the esophagus or gastric cardia were treatedby resection and intraluminal elastic circularligation for esophagogastric anastomosis. Thispresent study advances the results d...Between 1981 and 1988, 234 cases of cancerof the esophagus or gastric cardia were treatedby resection and intraluminal elastic circularligation for esophagogastric anastomosis. Thispresent study advances the results described inour earlier study. The details of technicalrefinements are here reported, based on the展开更多
Triple-negative breast cancer(TNBC)is currently the worst prognostic subtype of breast cancer,and there is no effective treatment other than chemotherapy.Processing of precursors 1(POP1)is the most substantially up-re...Triple-negative breast cancer(TNBC)is currently the worst prognostic subtype of breast cancer,and there is no effective treatment other than chemotherapy.Processing of precursors 1(POP1)is the most substantially up-regulated RNA-binding protein(RBP)in TNBC.However,the role of POP1 in TNBC remains clarified.A series of molecular biological experiments in vitro and invivo and clinical correlation analyses were conducted to clarify the biological function and regulatory mechanism of POP1 in TNBC.Here,we identified that POP1 is significantly up-regulated in TNBC and associated with poor prognosis.We further demonstrate that POP1 promotes the cell cycle and proliferation of TNBC in vitro and vivo.Mechanistically,POP1 directly binds to the coding sequence(CDS)region of CDKN1AmRNA and degrades it.The degradation process depends on the N6-methyladenosine(m6A)modification at the 497th site of CDKN1A and the recognition of this modification by YTH N6-methyladenosine RNA binding protein 2(YTHDF2).Moreover,the m6A inhibitor STM2457 potently impaired the proliferation of POP1-overexpressed TNBC cells and improved the sensitivity to paclitaxel.In summary,our findings reveal the pivotal role of POP1in promoting TNBC proliferation by degrading the mRNA of CDKN1A and that inhibition of m6A with STM2457 is a promising therapeutic strategy for TNBC.展开更多
文摘Between 1981 and 1988, 234 cases of cancerof the esophagus or gastric cardia were treatedby resection and intraluminal elastic circularligation for esophagogastric anastomosis. Thispresent study advances the results described inour earlier study. The details of technicalrefinements are here reported, based on the
基金supported by the National Natural Science Foundation of China(no.82273399,H.T.).
文摘Triple-negative breast cancer(TNBC)is currently the worst prognostic subtype of breast cancer,and there is no effective treatment other than chemotherapy.Processing of precursors 1(POP1)is the most substantially up-regulated RNA-binding protein(RBP)in TNBC.However,the role of POP1 in TNBC remains clarified.A series of molecular biological experiments in vitro and invivo and clinical correlation analyses were conducted to clarify the biological function and regulatory mechanism of POP1 in TNBC.Here,we identified that POP1 is significantly up-regulated in TNBC and associated with poor prognosis.We further demonstrate that POP1 promotes the cell cycle and proliferation of TNBC in vitro and vivo.Mechanistically,POP1 directly binds to the coding sequence(CDS)region of CDKN1AmRNA and degrades it.The degradation process depends on the N6-methyladenosine(m6A)modification at the 497th site of CDKN1A and the recognition of this modification by YTH N6-methyladenosine RNA binding protein 2(YTHDF2).Moreover,the m6A inhibitor STM2457 potently impaired the proliferation of POP1-overexpressed TNBC cells and improved the sensitivity to paclitaxel.In summary,our findings reveal the pivotal role of POP1in promoting TNBC proliferation by degrading the mRNA of CDKN1A and that inhibition of m6A with STM2457 is a promising therapeutic strategy for TNBC.
