MARCH2对卵巢癌HO-8910细胞自噬及生长的影响
Effect of MARCH2 on Autophagy and Growth of Ovarian Cancer HO-8910 Cells
DOI: 10.12677/ACM.2019.910180, PDF,    国家自然科学基金支持
作者: 夏 丹：山东医学高等专科学校病理教研室，山东 临沂
关键词: MARCH2；自噬；HO-8910细胞；卵巢癌；MARCH2； Autophagy； HO-8910 Cells； Ovarian Cancer
摘要: Membrane-associated RING-CH protein 2 (MARCH2)是MARCH家族成员之一，主要负责囊泡运输，本研究构建了过表达MARCH2和沉默MARCH2的HO-8910细胞系，目的是为了研究MARCH2对卵巢癌细胞自噬及生长的影响。研究发现，沉默MARCH2可以促进自噬体的形成和自噬流，相反，过表达MARCH2会抑制自噬体的形成和自噬流，进一步研究发现，MARCH2缺失介导的自噬作用在ULK1和PIK3C3-BECN1复合物的上游。此外，沉默MARCH2可以抑制体外细胞增殖，亦会抑制体外裸鼠移植瘤的生长。这些效应与自噬信号的活化有关系。
Abstract: MARCH2 is a member of MARCH family, which is mainly responsible for vesicle transport. In this study, we constructed an over-expressed MARCH2 and silenced MARCH2 HO-8910 cell line to study the effect of MARCH2 on the autophagy level of ovarian cancer cells. It was found that knockout of MARCH2 could promote the formation of autophagosome and autophagic flow. On the contrary, overexpression of MARCH2 could inhibit the formation of autophagosome and autophagic flow. Further studies showed that the absence of MARCH2 mediated autophagy upstream of ULK1 and PIK3C3 complexes. In addition, MARCH2 deficiency can inhibit cell proliferation in vitro and the growth of xenografts in nude mice. These effects are related to the activation of autophagic signals.
文章引用：夏丹. MARCH2对卵巢癌HO-8910细胞自噬及生长的影响[J]. 临床医学进展, 2019, 9(10): 1163-1173. https://doi.org/10.12677/ACM.2019.910180

参考文献

[1] He, C. and Klionsky, D.J. (2009) Regulation Mechanisms and Signaling Pathways of Autophagy. Annual Review of Genetics, 43, 67-93. [Google Scholar] [CrossRef] [PubMed]
[2] Levine, B., Mizushima, N. and Virgin, H.W. (2011) Autophagy in Immunity and Inflammation. Nature, 469, 323-335. [Google Scholar] [CrossRef] [PubMed]
[3] Mizushima, N., Levine, B., Cuervo, A.M. and Klionsky, D.J. (2008) Autophagy Fights Disease through Cellular Self-Digestion. Nature, 451, 1069-1075. [Google Scholar] [CrossRef] [PubMed]
[4] Dunlop, E.A. and Tee, A.R. (2014) mTOR and Autophagy: A Dynamic Relationship Governed by Nutrients and Energy. Seminars in Cell & Developmental Biology, 36, 121-129. [Google Scholar] [CrossRef] [PubMed]
[5] Heras-Sandoval, D., Perez-Rojas, J.M., Hernandez-Damian, J. and Pedraza-Chaverri, J. (2014) The Role of PI3K/AKT/mTOR Pathway in the Modulation of Autophagy and the Clearance of Protein Aggregates in Neurodegeneration. Cellular Signalling, 26, 2694-2701. [Google Scholar] [CrossRef] [PubMed]
[6] Bartee, E., Mansouri, M., Hovey, N.B., Gouveia, K. and Fruh, K. (2004) Downregulation of Major Histocompatibility Complex Class I Byhuman Ubiquitin Ligases Related Toviral Immune Evasion Proteins. Journal of Virology, 78, 1109-1120. [Google Scholar] [CrossRef] [PubMed]
[7] Boutell, C., Sadis, S. and Everett, R.D. (2002) Herpes Simplex Virus Type 1 Immediate-Early Protein ICP0 and Is Isolated RING Finger Domain Act as Ubiquitin E3 Ligases in Vitro. Journal of Virology, 76, 841-850. [Google Scholar] [CrossRef] 
[8] Nakamura, N., Fukuda, H., Kato, A. and Hirose, S. (2005) MARCH-Iiisasyntaxin-6-Binding Protein Involved in Endosomal Trafficking. Molecular Biology of the Cell, 16, 1696-1710. [Google Scholar] [CrossRef] [PubMed]
[9] Cao, Z., Huett, A., Kuballa, P., Giallourakis, C. and Xavier, R.J. (2008) DLG1 Is an Anchor for the E3 Ligase MARCH2 at Sites of Cell-Cell Contact. Cellular Signalling, 20, 73-82. [Google Scholar] [CrossRef] [PubMed]
[10] Han, S.O., Xiao, K., Kim, J., Wu, J.H., Wisler, J.W., Nakamura, N., et al. (2012) MARCH2 Promotes Endocytosis and Lysosomal Sorting of Carvedilol-Bound Beta(2)-Adrenergic Receptors. The Journal of Cell Biology, 199, 817-830. [Google Scholar] [CrossRef] [PubMed]
[11] Cheng, J. and Guggino, W. (2013) Ubiquitination and Degradation of CFTR by the E3 Ubiquitin Ligase MARCH2 through Its Association with Adaptor Proteins CAL and STX6. PLoS ONE, 8, e68001. [Google Scholar] [CrossRef] [PubMed]
[12] Xia, D., Qu, L., Li, G., Hongdu, B., Xu, C., Lin, X., et al. (2016) MARCH2 Regulates Autophagy by Promoting CFTR Ubiquitination and Degradation and PIK3CA-AKT-MTOR Signaling. Autophagy, 12, 1614-1630. [Google Scholar] [CrossRef] [PubMed]
[13] Kugimiya, N., Nishimoto, A., Hosoyama, T., Ueno, K., Enoki, T., Li, T.S., et al. (2015) The c-MYC-ABCB5axis Plays a Pivotal Role in 5-Fluorouracil Resistance in Human Colon Cancer Cells. Journal of Cellular and Molecular Medicine, 19, 1569-1581. [Google Scholar] [CrossRef] [PubMed]
[14] Kimmelman, A.C. (2011) The Dynamic Nature of Autophagy in Cancer. Genes & Development, 25, 1999-2010. [Google Scholar] [CrossRef] [PubMed]
[15] Takamura, A., Komatsu, M., Hara, T., et al. (2011) Autopha-gy-Deficient Mice Develop Multiple Liver Tumors. Genes & Development, 25, 795-800. [Google Scholar] [CrossRef] [PubMed]
[16] Inami, Y., Waguri, S., Sakamoto, A., et al. (2011) Persistent Activation of Nrf2 through p62 in Hepatocellular Carcinoma Cells. The Journal of Cell Biology, 193, 275-284. [Google Scholar] [CrossRef] [PubMed]
[17] White, E. (2015) The Role for Autophagy in Cancer. Journal of Clinical Investigation, 125, 42-46. [Google Scholar] [CrossRef] 
[18] Mathew, R., Karp, C.M., Beaudoin, B., et al. (2009) Autophagy Sup-presses Tumorigenesis through Elimination of p62. Cell, 137, 1062-1075.
[19] Li, L., Shen, C., Nakamura, E., et al. (2013) SQSTM1 Is a Pathogenic Target of 5q Copy Number Gains in Kidney Cancer. Cancer Cell, 24, 738-750. [Google Scholar] [CrossRef] [PubMed]
[20] Duran, A., Linares, J.F., Galvez, A.S., et al. (2008) The Signaling Adaptor p62 Is an Important NF-kappaB Mediator in Tumorigenesis. Cancer Cell, 13, 343-354. [Google Scholar] [CrossRef] [PubMed]

为你推荐