BACKGROUND Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy(PHx).At present,there is a lack of recognized safe,effective,and stable drugs to promote liver regen...BACKGROUND Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy(PHx).At present,there is a lack of recognized safe,effective,and stable drugs to promote liver regeneration.It has been reported that vagus nerve signaling is beneficial to liver regeneration,but the potential mechanism at play here is not fully understood.AIM To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx.METHODS A PHx plus hepatic vagotomy(Hv)mouse model was established.The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice.In order to further investigate the role of interleukin(IL)-22 in liver regeneration inhibition mediated by Hv,the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured.The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx.RESULTS Compared to control-group mice,Hv mice showed severe liver injury and weakened liver regeneration after PHx.Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3(STAT3)pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx.Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury,while treatment with IL-22 binding protein(an inhibitor of IL-22 signaling)reduce the concentration of IL-22 induced by PHx,inhibits the activation of the STAT3 signaling pathway in the liver after PHx,thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice.CONCLUSION Hv attenuates liver regeneration after hepatectomy,and the mechanism may be related to the fact that Hv downregulates the production of IL-22,then blocks activation of the STAT3 pathway.展开更多
Background Considerable evidence suggests that phosphatase of regenerating liver-3 （PRL-3） plays multiple roles in cancer metastasis; however, the molecular mechanisms remain largely unknown. The aim of this study w...Background Considerable evidence suggests that phosphatase of regenerating liver-3 （PRL-3） plays multiple roles in cancer metastasis; however, the molecular mechanisms remain largely unknown. The aim of this study was to identify proteins associated with PRL-3-promoted colon cancer metastasis, by comparative proteomic analysis. Methods Proteomes of human colon cancer LoVo cells transfected with PRL-3 gene （LoVo-PRL-3） or empty vector PAcGFP-C3 （LoVo-control） were compared using 2D gel electrophoresis. Proteins that varied significantly in concentration were selected and identified using mass spectrometry. Expression of translationally controlled tumor protein （TCTP） mRNA and protein in LoVo-PRL-3 and LoVo-control cells was detected by real-time PCR and Western blotting. Small interfering RNA （siRNA） targeting TCTP was used for silencing TCTP expression in LoVo-PRL-3 cells. Functional significance of TCTP in PRL-3-promoted colon cancer cell proliferation, migration and invasion was investigated by Cell Counting Kit-8 assay and transwell chamber. Results Seventeen proteins displaying significant and reproducible differences between LoVo-PRL-3 and LoVo-control cells were identified. Ten proteins were upregulated and seven were downregulated in LoVo-PRL-3 cells when compared with LoVo-control cells. Eight identified proteins are associated with distinct steps of tumor metastasis： ubiquitin-like protein ISG15, interleukin-18, TCTP, serpin B5, annexin A3, macrophage-capping protein, ATP-dependent RNA helicase DDX3X, and cathepsin D. Real-time PCR and Western blotting results showed that both TCTP mRNA and protein were significantly increased in LoVo-PRL-3 cells compared to LoVo-control cells. Transfection with TCTP siRNA significantly reduced the expression of both mRNA and protein levels of TCTP in LoVo-PRL-3 cells. Knockdown of TCTP by siRNA inhibited PRL-3-promoted proliferation, migration and invasion of LoVo-PRL-3 cells. Conclusion Our results imply that TCTP might be a mediator of PRL-3-promoted proliferation, migration and invasion of human colon cancer cells.展开更多
目的:检测肝再生磷酸酶3(PRL-3)mRNA在胃癌、癌旁正常组织及其转移灶中的表达,探讨其与胃癌发生发展以及侵袭转移的生物学行为之间的关系。方法:半定量PCR测定22例胃癌组织及其相对应的癌旁正常组织、6例远处转移灶PRL-3 mRNA相对表达水...目的:检测肝再生磷酸酶3(PRL-3)mRNA在胃癌、癌旁正常组织及其转移灶中的表达,探讨其与胃癌发生发展以及侵袭转移的生物学行为之间的关系。方法:半定量PCR测定22例胃癌组织及其相对应的癌旁正常组织、6例远处转移灶PRL-3 mRNA相对表达水平,并分析其表达水平与临床病理学指标的关系。结果:22例胃癌组织中PRL-3基因表达量较相应癌旁正常组织中高,但差异无统计学意义(0.95±0.24 vs 0.85±0.27,P>0.05)。6例转移灶PRL-3基因表达量(2.04±0.44)显著高于原发肿瘤(1.26±0.26)(P<0.05)。PRL-3基因表达水平与肿瘤远处转移有相关性(P<0.05),而与肿瘤大小、分化程度、浸润深度及性别无关(P>0.05)。结论:PRL-3基因在胃癌恶性进展中起重要作用,PRL-3可能成为判断胃癌转移高危因素的一个生物学标志物。展开更多
基金Supported by the Natural Science Foundation of Zhejiang Province,No.LQ20H310002the Scientific Technology Projects of Health and Medicine of Zhejiang Province,No.2020KY308and the Huzhou Science and Technology Fund,No.2020GY39.
文摘BACKGROUND Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy(PHx).At present,there is a lack of recognized safe,effective,and stable drugs to promote liver regeneration.It has been reported that vagus nerve signaling is beneficial to liver regeneration,but the potential mechanism at play here is not fully understood.AIM To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx.METHODS A PHx plus hepatic vagotomy(Hv)mouse model was established.The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice.In order to further investigate the role of interleukin(IL)-22 in liver regeneration inhibition mediated by Hv,the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured.The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx.RESULTS Compared to control-group mice,Hv mice showed severe liver injury and weakened liver regeneration after PHx.Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3(STAT3)pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx.Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury,while treatment with IL-22 binding protein(an inhibitor of IL-22 signaling)reduce the concentration of IL-22 induced by PHx,inhibits the activation of the STAT3 signaling pathway in the liver after PHx,thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice.CONCLUSION Hv attenuates liver regeneration after hepatectomy,and the mechanism may be related to the fact that Hv downregulates the production of IL-22,then blocks activation of the STAT3 pathway.
文摘Background Considerable evidence suggests that phosphatase of regenerating liver-3 （PRL-3） plays multiple roles in cancer metastasis; however, the molecular mechanisms remain largely unknown. The aim of this study was to identify proteins associated with PRL-3-promoted colon cancer metastasis, by comparative proteomic analysis. Methods Proteomes of human colon cancer LoVo cells transfected with PRL-3 gene （LoVo-PRL-3） or empty vector PAcGFP-C3 （LoVo-control） were compared using 2D gel electrophoresis. Proteins that varied significantly in concentration were selected and identified using mass spectrometry. Expression of translationally controlled tumor protein （TCTP） mRNA and protein in LoVo-PRL-3 and LoVo-control cells was detected by real-time PCR and Western blotting. Small interfering RNA （siRNA） targeting TCTP was used for silencing TCTP expression in LoVo-PRL-3 cells. Functional significance of TCTP in PRL-3-promoted colon cancer cell proliferation, migration and invasion was investigated by Cell Counting Kit-8 assay and transwell chamber. Results Seventeen proteins displaying significant and reproducible differences between LoVo-PRL-3 and LoVo-control cells were identified. Ten proteins were upregulated and seven were downregulated in LoVo-PRL-3 cells when compared with LoVo-control cells. Eight identified proteins are associated with distinct steps of tumor metastasis： ubiquitin-like protein ISG15, interleukin-18, TCTP, serpin B5, annexin A3, macrophage-capping protein, ATP-dependent RNA helicase DDX3X, and cathepsin D. Real-time PCR and Western blotting results showed that both TCTP mRNA and protein were significantly increased in LoVo-PRL-3 cells compared to LoVo-control cells. Transfection with TCTP siRNA significantly reduced the expression of both mRNA and protein levels of TCTP in LoVo-PRL-3 cells. Knockdown of TCTP by siRNA inhibited PRL-3-promoted proliferation, migration and invasion of LoVo-PRL-3 cells. Conclusion Our results imply that TCTP might be a mediator of PRL-3-promoted proliferation, migration and invasion of human colon cancer cells.
文摘目的:检测肝再生磷酸酶3(PRL-3)mRNA在胃癌、癌旁正常组织及其转移灶中的表达,探讨其与胃癌发生发展以及侵袭转移的生物学行为之间的关系。方法:半定量PCR测定22例胃癌组织及其相对应的癌旁正常组织、6例远处转移灶PRL-3 mRNA相对表达水平,并分析其表达水平与临床病理学指标的关系。结果:22例胃癌组织中PRL-3基因表达量较相应癌旁正常组织中高,但差异无统计学意义(0.95±0.24 vs 0.85±0.27,P>0.05)。6例转移灶PRL-3基因表达量(2.04±0.44)显著高于原发肿瘤(1.26±0.26)(P<0.05)。PRL-3基因表达水平与肿瘤远处转移有相关性(P<0.05),而与肿瘤大小、分化程度、浸润深度及性别无关(P>0.05)。结论:PRL-3基因在胃癌恶性进展中起重要作用,PRL-3可能成为判断胃癌转移高危因素的一个生物学标志物。
