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| 1 | GOLPH3通过WNT信号通路调控胶质瘤细胞增殖及其机制的研究显示文摘目的探讨高尔基体磷蛋白3(GOLPH3)、WNT/β-catenin信号通路对胶质瘤细胞增殖的影响及机制。方法采用脂质体转染法将siRNA转染至胶质瘤U251细胞中,将转染negative control siRNA oligo和各siRNA oligo的细胞分别设为阴性对照组(siNC组)和下调组(siGOLPH3组、siWNT2组、siβ-catenin组)。采用蛋白质印迹法(Western blot)检测相关蛋白表达水平,EdU法检测对胶质瘤细胞增殖的影响。结果siGOLPH3组细胞中WNT2蛋白相对表达量低于siNC组,siWNT2组细胞中β-catenin蛋白相对表达量低于siNC组,差异均有统计学意义(P﹤0.05)。siWNT2组细胞中GOLPH3蛋白相对表达量与siNC组比较,差异无统计学意义(P﹥0.05)。与siNC组相比,siGOLPH3组、siWNT2组、siβ-catenin组细胞增殖率均降低,差异均有统计学意义(P﹤0.05)。结论下调GOLPH3后可以降低WNT2的蛋白表达水平,下调WNT2后可以降低其下游β-catenin蛋白的表达水平,下调GOLPH3、WNT2、β-catenin均能抑制胶质瘤细胞的增殖。GOLPH3可能通过WNT/β-catenin信号通路影响胶质瘤细胞的增殖。 | 张猛 沙林 马庆防 安刚 于如同 黎军 | 2019 | 癌症进展2019，17，16： | 6 |
| 2 | Parkinson’s disease-associated VPS35 mutant reduces mitochondrial membrane potential and impairs PINK1/Parkinmediated mitophagy显示文摘Background:Mitochondrial dysfunction plays a prominent role in the pathogenesis of Parkinson’s disease(PD),and several genes linked to familial PD,including PINK1(encoding PTEN-induced putative kinase 1[PINK1])and PARK2(encoding the E3 ubiquitin ligase Parkin),are directly involved in processes such as mitophagy that maintain mitochondrial health.The dominant p.D620N variant of vacuolar protein sorting 35 ortholog(VPS35)gene is also associated with familial PD but has not been functionally connected to PINK1 and PARK2.Methods:To better mimic and study the patient situation,we used CRISPR-Cas9 to generate heterozygous human SH-SY5Y cells carrying the PD-associated D620N variant of VPS35.These cells were treated with a protonophore carbonyl cyanide m-chlorophenylhydrazone(CCCP)to induce the PINK1/Parkin-mediated mitophagy,which was assessed using biochemical and microscopy approaches.Results:Mitochondria in the VPS35-D620N cells exhibited reduced mitochondrial membrane potential and appeared to already be damaged at steady state.As a result,the mitochondria of these cells were desensitized to the CCCPinduced collapse in mitochondrial potential,as they displayed altered fragmentation and were unable to accumulate PINK1 at their surface upon this insult.Consequently,Parkin recruitment to the cell surface was inhibited and initiation of the PINK1/Parkin-dependent mitophagy was impaired.Conclusion:Our findings extend the pool of evidence that the p.D620N mutation of VPS35 causes mitochondrial dysfunction and suggest a converging pathogenic mechanism among VPS35,PINK1 and Parkin in PD. | Kai Yu Ma Michiel R.Fokkens Fulvio Reggiori Muriel Mari Dineke S.Verbeek | 2021 | Translational Neurodegeneration2021，10，2： | 3 |
| 3 | Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway显示文摘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. | Yi Liu Haijun Deng Li Liang Guiji Zhang Jie Xia Keyue Ding Ni Tang Kai Wang | 2021 | Genes & Diseases2021，8，2： | 2 |
| 4 | Retrograde trafficking of VMAT2 and its role in protein stability in non-neuronal cells显示文摘Increasing evidence suggests that the impaired neuroprotection of vesicular monoamine transporter 2(VMAT2)contributes to the pathogenesis of Parkinson's disease.That has been linked to aberrant subcellular retrograde trafficking as strongly indicated by recent genomic studies on familial Parkinson's diseases.However,whether VMAT2 function is regulated by retrograde trafficking is unknown.By using biochemistry and cell biology approaches,we have shown that VMAT2 was stringently localized to the trans-Golgi network and underwent retrograde trafficking in non-neuronal cells.The transporter also interacted with the key component of retromer,Vps35,biochemically and subcellularly.Using specific siRNA,we further showed that Vps35 depletion altered subcellular localization of VMAT2.Moreover,siRNA-mediated Vps35 knockdown also decreased the stability of VMAT2 as demonstrated by the reduced half-life.Thus,our work suggested that altered vesicular trafficking of VMAT2 may play a vital role in neuroprotection of the transporter as well as in the pathogenesis of Parkinson's disease. | Qiuzi Wu Hongfei Xu Wei Wang Fei Chang Yu Jiang Yongjian Liu | 2016 | The Journal of Biomedical Research2016，30，6： | 1 |
| 5 | Mutations in GBA,SNCA,and VPS35 are not associated with Alzheimer's disease in a Chinese population:a case-control study显示文摘SNCA,GBA,and VPS35 are three common genes associated with Parkinson's disease.Previous studies have shown that these three genes may be associated with Alzheimer's disease(AD).However,it is unclear whether these genes increase the risk of AD in Chinese populations.In this study,we used a targeted gene sequencing panel to screen all the exon regions and the nearby sequences of GBA,SNCA,and VPS35 in a cohort including 721 AD patients and 365 healthy controls from China.The results revealed that neither common variants nor rare variants of these three genes were associated with AD in a Chinese population.These findings suggest that the mutations in GBA,SNCA,and VPS35 are not likely to play an important role in the genetic susceptibility to AD in Chinese populations.The study was approved by the Ethics Committee of Xiangya Hospital,Central South University,China on March 9,2016(approval No.201603198). | Ya-Fei Wen Xue-Wen Xiao Lu Zhou Ya-Ling Jiang Yuan Zhu Li-Na Guo Xin Wang Hui Liu Ya-Fang Zhou Jun-Ling Wang Xin-Xin Liao Lu Shen Bin Jiao | 2022 | Neural Regeneration Research2022，17，3： | 0 |
| 6 | VPS35在肿瘤发生与转移中的作用及机制研究显示文摘VPS35是Retromer复合体的重要组成部分,在内吞体蛋白分选转运过程中有重要作用.最近研究表明,VPS35作为一种新的致癌基因,在多种肿瘤中高表达,调控多种因子及通路,从而影响肿瘤的发生发展和转移.本文综述了目前VPS35调控肿瘤相关因子及通路进而促进肿瘤发生与转移的最新研究进展,总结讨论了VPS35在肿瘤发生与转移中的作用机制,为将来深入研究VPS35/Retromer组分在肿瘤发生转移中的作用及机制提供借鉴与参考. | 姚欣怡 董瑞 郝庆刚 沈俊岭 刘楠 孙建伟 | 2023 | 中国科学:生命科学2023，53，8： | 0 |
| 7 | VPS35在恶性肿瘤中的作用显示文摘囊泡分选蛋白35(vacuolar protein sorting 35,VPS35)是一种逆转运蛋白,负责货物蛋白的分选和运输,与阿尔茨海默病、帕金森病等神经退行性疾病有关。VPS35广泛参与多种信号通路,在细胞的生长、增殖、自噬和凋亡等方面具有重要的作用。VPS35在多种恶性肿瘤中高表达,并通过不同机制调节肿瘤细胞的增殖、迁移、侵袭能力。本文主要围绕VPS35的结构特征、参与的信号通路及VPS35在恶性肿瘤中发挥的作用进行综述,旨在为今后的临床研究提供理论依据。 | 高远飞 魏成 张栋岩 邓成伍 魏相相 王琛 | 2023 | 生命的化学2023，43，10： | 0 |
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