Vesicle Protein Sorting 35(VPS35)is a novel oncogene that promotes tumor growth through the PI3K/AKT signaling in hepatocellular carcinoma(HCC).However,the role of VPS35 in HCC metastasis and the underlying mechanisms...Vesicle Protein Sorting 35(VPS35)is a novel oncogene that promotes tumor growth through the PI3K/AKT signaling in hepatocellular carcinoma(HCC).However,the role of VPS35 in HCC metastasis and the underlying mechanisms remain largely unclear.In this study,we observed that overexpression of VPS35 enhanced hepatoma cell invasion and metastasis by inducing epithelialemesenchymal transition(EMT)-related gene expression.Conversely,knockout of VPS35 significantly inhibited hepatoma cell migration and invasion.Furthermore,depletion of VPS35 decreased the lung metastasis of HCC in nude mice.By transcriptome analysis,we determined that VPS35 promoted HCC metastasis by activating the Wnt/non-canonical planar cell polarity(PCP)pathway.Mechanistically,VPS35 activated the PCP pathway by regulating membrane sorting and trafficking of Frizzled-2(FZD2)and ROR1 in hepatoma cells.Collectively,our results indicate that VPS35 promotes HCC metastasis via enhancing the Wnt/PCP signaling,thus providing a potential prognostic marker and therapeutic target for HCC.展开更多
Schwann cells play a critical role in peripheral nerve regeneration through dedifferentiation and proliferation. In a previous study, we performed microarray analysis of the sciatic nerve after injury. Accordingly, we...Schwann cells play a critical role in peripheral nerve regeneration through dedifferentiation and proliferation. In a previous study, we performed microarray analysis of the sciatic nerve after injury. Accordingly, we predicted that long non-coding RNA NONMMUG014387 may promote Schwann cell proliferation after peripheral nerve injury, as bioinformatic analysis revealed that the target gene of NONMMUG014387 was collagen triple helix repeat containing 1（Cthrc1）. Cthrc1 may promote cell proliferation in a variety of cells by activating Wnt/PCP signaling. Nonetheless, bioinformatic analysis still needs to be verified by biological experiment. In this study, the candidate long non-coding RNA, NONMMUG014387, was overexpressed in mouse Schwann cells by recombinant adenovirus transfection. Plasmid p HBAd-MCMV-GFP-NONMMUG014387 and p HBAd-MCMV-GFP were transfected into Schwann cells. Schwann cells were divided into three groups： control（Schwann cells without intervention）, Ad-GFP（Schwann cells with GFP overexpression）, and Ad-NONMMUGO148387（Schwann cells with GFP and NONMMUGO148387 overexpression）. Cell Counting Kit-8 assay was used to evaluate proliferative capability of mouse Schwann cells after NONMMUG014387 overexpression. Polymerase chain reaction and western blot assay were performed to investigate target genes and downstream pathways of NONMMUG014387. Cell proliferation was significantly increased in Schwann cells overexpressing lnc RNA NONMMUG014387 compared with the other two groups. Further, compared with the control group, m RNA and protein levels of Cthrc1, Wnt5 a, ROR2, Rho A, Rac1, JNK, and ROCK were visibly up-regulated in the Ad-NONMMUGO148387 group. Our findings confirm that long non-coding RNA NONMMUG014387 can promote proliferation of Schwann cells surrounding the injury site through targeting Cthrc1 and activating the Wnt/PCP pathway.展开更多
The phenomenon of planar cell polarity is critically required for a myriad of morphogenetic processes in metazoan and is accurately controlled by several conserved modules.Six“core”proteins,including Friz zled,Flami...The phenomenon of planar cell polarity is critically required for a myriad of morphogenetic processes in metazoan and is accurately controlled by several conserved modules.Six“core”proteins,including Friz zled,Flamingo(Celsr),Van Gogh(Vangl),Dishevelled,Prickle,and Diego(Ankrd6),are major components of the Wnt/planar cell polarity pathway.The Fat/Dchs protocadherins and the Scrib polarity complex also function to instruct cellular polarization.In vertebrates,all these pathways are essential for tissue and organ morphogenesis,such as neural tube closure,left-right symmetry breaking,heart and gut morphogenesis,lung and kidney branching,stereociliary bundle orientation,and proximal-distal limb elongation.Mutations in planar polarity genes are closely linked to various congenital diseases.Striking advances have been made in deciphering their contribution to the establishment of spatially oriented pattern in developing or gans and the maintenance of tissue homeostasis.The challenge remains to clarify the complex interplay of different polarity pathways in organogenesis and the link of cell polarity to cell fate specification.Inter disciplinary approaches are also important to understand the roles of mechanical forces in coupling cellular polarization and differentiation.This review outlines current advances on planar polarity regulators in asymmetric organ formation,with the aim to identify questions that deserve further investigation.展开更多
基金This work was supported by National Natural Science Foundation of China(grant numbers 81872270 and 81572683 to NT),the Natural Science Foundation Project of Chongqing(cstc2019jcyj-msxmX0587 to KW),the Science and Technology Research Program of Chongqing Municipal Education Commission(Grant number KJQN201900429 to KW),the Major National S&T program(2017ZX10202203-004 to NT),Natural Science Foundation Project of CQ CSTC(cstc2018jcyjAX0254 to NT),and the Leading Talent Program of CQ CSTC(CSTCCXLJRC201719 to NT).
文摘Vesicle Protein Sorting 35(VPS35)is a novel oncogene that promotes tumor growth through the PI3K/AKT signaling in hepatocellular carcinoma(HCC).However,the role of VPS35 in HCC metastasis and the underlying mechanisms remain largely unclear.In this study,we observed that overexpression of VPS35 enhanced hepatoma cell invasion and metastasis by inducing epithelialemesenchymal transition(EMT)-related gene expression.Conversely,knockout of VPS35 significantly inhibited hepatoma cell migration and invasion.Furthermore,depletion of VPS35 decreased the lung metastasis of HCC in nude mice.By transcriptome analysis,we determined that VPS35 promoted HCC metastasis by activating the Wnt/non-canonical planar cell polarity(PCP)pathway.Mechanistically,VPS35 activated the PCP pathway by regulating membrane sorting and trafficking of Frizzled-2(FZD2)and ROR1 in hepatoma cells.Collectively,our results indicate that VPS35 promotes HCC metastasis via enhancing the Wnt/PCP signaling,thus providing a potential prognostic marker and therapeutic target for HCC.
基金supported by a grant from Student’s Platform for Innovation and Entrepreneurship Training Program in China,No.201610062009the National Natural Science Foundation of China(Key Program),No.81330042+1 种基金a grant from the Special Program for Sino-Russian Joint Research Sponsored by the Ministry of Science and Technology,China,No.2014DFR31210a grant from the Key Program Sponsored by the Tianjin Science and Technology Committee of China,No.13RCGFSY19000,14ZCZDSY00044
文摘Schwann cells play a critical role in peripheral nerve regeneration through dedifferentiation and proliferation. In a previous study, we performed microarray analysis of the sciatic nerve after injury. Accordingly, we predicted that long non-coding RNA NONMMUG014387 may promote Schwann cell proliferation after peripheral nerve injury, as bioinformatic analysis revealed that the target gene of NONMMUG014387 was collagen triple helix repeat containing 1（Cthrc1）. Cthrc1 may promote cell proliferation in a variety of cells by activating Wnt/PCP signaling. Nonetheless, bioinformatic analysis still needs to be verified by biological experiment. In this study, the candidate long non-coding RNA, NONMMUG014387, was overexpressed in mouse Schwann cells by recombinant adenovirus transfection. Plasmid p HBAd-MCMV-GFP-NONMMUG014387 and p HBAd-MCMV-GFP were transfected into Schwann cells. Schwann cells were divided into three groups： control（Schwann cells without intervention）, Ad-GFP（Schwann cells with GFP overexpression）, and Ad-NONMMUGO148387（Schwann cells with GFP and NONMMUGO148387 overexpression）. Cell Counting Kit-8 assay was used to evaluate proliferative capability of mouse Schwann cells after NONMMUG014387 overexpression. Polymerase chain reaction and western blot assay were performed to investigate target genes and downstream pathways of NONMMUG014387. Cell proliferation was significantly increased in Schwann cells overexpressing lnc RNA NONMMUG014387 compared with the other two groups. Further, compared with the control group, m RNA and protein levels of Cthrc1, Wnt5 a, ROR2, Rho A, Rac1, JNK, and ROCK were visibly up-regulated in the Ad-NONMMUGO148387 group. Our findings confirm that long non-coding RNA NONMMUG014387 can promote proliferation of Schwann cells surrounding the injury site through targeting Cthrc1 and activating the Wnt/PCP pathway.
基金supported by grants from the National Natural Science Foundation of China(grant number 32070813)the French Muscular Dystrophy Association (AFM-Telethon grant number 23545)+1 种基金the Centre National de la Recherche Scientifiquethe Sorbonne University
文摘The phenomenon of planar cell polarity is critically required for a myriad of morphogenetic processes in metazoan and is accurately controlled by several conserved modules.Six“core”proteins,including Friz zled,Flamingo(Celsr),Van Gogh(Vangl),Dishevelled,Prickle,and Diego(Ankrd6),are major components of the Wnt/planar cell polarity pathway.The Fat/Dchs protocadherins and the Scrib polarity complex also function to instruct cellular polarization.In vertebrates,all these pathways are essential for tissue and organ morphogenesis,such as neural tube closure,left-right symmetry breaking,heart and gut morphogenesis,lung and kidney branching,stereociliary bundle orientation,and proximal-distal limb elongation.Mutations in planar polarity genes are closely linked to various congenital diseases.Striking advances have been made in deciphering their contribution to the establishment of spatially oriented pattern in developing or gans and the maintenance of tissue homeostasis.The challenge remains to clarify the complex interplay of different polarity pathways in organogenesis and the link of cell polarity to cell fate specification.Inter disciplinary approaches are also important to understand the roles of mechanical forces in coupling cellular polarization and differentiation.This review outlines current advances on planar polarity regulators in asymmetric organ formation,with the aim to identify questions that deserve further investigation.
