| Peer-Reviewed

Effect of AGO2 Depletion on Cell Migration of A172 Brain Cancer Cell

Received: 7 September 2020    Accepted: 29 September 2020    Published: 16 October 2020
Views:       Downloads:
Abstract

AGO2, a protein-coding and miRNA regulating gene, has recently been identified as a phenomenal biomarker in cancer development research. Its role varies in different cancers, acting as either a tumor suppressor or an oncogene. However, no research has been conducted on the correlation between AGO2 and brain cancer yet. The aim of this study was to define the association of AGO2 amplification and brain cancer patient’s survival and to investigate the functional role of AGO2 in brain cancer cell migration. 20 brain cancer studies with a total of 6164 patient samples via cBioPortal were analyzed. After the patients were divided into two groups: AGO2 amplified group and AGO2 non-amplified group, the overall patients’ survival rate was analyzed by Kaplan-Meier. The positive correlation between the AGO2 amplified group and survival rates was discovered. To find out how AGO2 amplification increased patients’ survival rates, we performed an in vitro assay to silence AGO2 expression using two siRNAs targeting AGO2 in A172 brain cancer cell line. The wound-healing assay was performed to show that both siRNAs targeting AGO2 promoted cell migration of A172. Therefore, AGO2 may function as a tumor suppressor and enhances survival rates of brain cancer patients by inhibiting cancer cell migration. Further investigation of the mechanisms affecting AGO2 dysregulation will provide insights into the molecular differences underpinning brain cancer patient’s survival rate.

Published in Cancer Research Journal (Volume 8, Issue 3)
DOI 10.11648/j.crj.20200803.12
Page(s) 51-56
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

AGO2, Brain Cancer, siRNA, RT-PCR, Cell Migration

References
[1] Barnholtz-Sloan JS, Ostrom QT, Cote D. Epidemiology of brain tumors. Neurol Clin. 2018; 36: 395–419.
[2] Miranda-Filho A, Piñeros M, Soerjomataram I, Deltour I, Bray F. Cancers of the brain and CNS: global patterns and trends in incidence. Neuro Oncol. 2017; 19: 270–280.
[3] Bondy ML, Scheurer ME, Malmer B, Barnholtz-Sloan JS, Davis FG, Il’yasova D, et al. Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium. Cancer. 2008; 113: 1953–1968. doi: 10.1002/cncr.23741.
[4] Höck J, Meister G. The Argonaute protein family. Genome Biol. 2008; 9: 210.
[5] Rand TA, Petersen S, Du F, Wang X. Argonaute2 cleaves the anti-guide strand of siRNA during RISC activation. Cell. 2005; 123: 621–629.
[6] Shekar PC, Naim A, Sarathi DP, Kumar S. Argonaute-2-null embryonic stem cells are retarded in self-renewal and differentiation. J Biosci. 2011; 36: 649–657.
[7] Wu S, Yu W, Qu X, Wang R, Xu J, Zhang Q, et al. Argonaute 2 promotes myeloma angiogenesis via microRNA dysregulation. J Hematol Oncol. 2014; 7: 40.
[8] Zhang X, Zhao H, Gao S, Wang W-C, Katiyar-Agarwal S, Huang H-D, et al. Arabidopsis Argonaute 2 regulates innate immunity via miRNA393 (∗)-mediated silencing of a Golgi-localized SNARE gene, MEMB12. Mol Cell. 2011; 42: 356–366.
[9] Bellissimo T, Tito C, Ganci F, Sacconi A, Masciarelli S, Di Martino G, et al. Argonaute 2 drives miR-145-5p-dependent gene expression program in breast cancer cells. Cell Death Dis. 2019; 10: 17.
[10] Zhang J, Fan X, Wang C, Liu B, Li Q, Zhou X. Up-regulation of Ago2 expression in gastric carcinoma. Med Oncol. 2013; 30: 628.
[11] Yoo NJ, Hur SY, Kim MS, Lee JY, Lee SH. Immunohistochemical analysis of RNA-induced silencing complex-related proteins AGO2 and TNRC6A in prostate and esophageal cancers. APMIS. 2010; 118: 271–276.
[12] Guo J, Lv J, Liu M, Tang H. miR-346 Up-regulates Argonaute 2 (AGO2) Protein Expression to Augment the Activity of Other MicroRNAs (miRNAs) and Contributes to Cervical Cancer Cell Malignancy. J Biol Chem. 2015; 290: 30342–30350.
[13] Yang F-Q, Huang J-H, Liu M, Yang F-P, Li W, Wang G-C, et al. Argonaute 2 is up-regulated in tissues of urothelial carcinoma of bladder. Int J Clin Exp Pathol. 2014; 7: 340–347.
[14] Laudadio I, Orso F, Azzalin G, Calabrò C, Berardinelli F, Coluzzi E, et al. AGO2 promotes telomerase activity and interaction between the telomerase components TERT and TERC. EMBO Rep. 2019; 20.
[15] Ye Z, Jin H, Qian Q. Argonaute 2: A novel rising star in cancer research. J Cancer. 2015; 6: 877–882.
[16] Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013; 6: pl1.
[17] Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012; 2: 401–404.
[18] Wang S, Sun X, Yi C, Zhang D, Lin X, Sun X, et al. AGO2 Negatively Regulates Type I Interferon Signaling Pathway by Competition Binding IRF3 with CBP/p300. Front Cell Infect Microbiol. 2017; 7: 195.
[19] Matsui A, Ihara T, Suda H, Mikami H, Semba K. Gene amplification: mechanisms and involvement in cancer. Biomol Concepts. 2013; 4: 567–582.
[20] Lockwood WW, Chari R, Coe BP, Girard L, Macaulay C, Lam S, et al. DNA amplification is a ubiquitous mechanism of oncogene activation in lung and other cancers. Oncogene. 2008; 27: 4615–4624.
[21] Jia Y, Chen L, Jia Q, Dou X, Xu N, Liao DJ. The well-accepted notion that gene amplification contributes to increased expression still remains, after all these years, a reasonable but unproven assumption. J Carcinog. 2016; 15: 3.
[22] Zhou Y, Chen L, Barlogie B, Stephens O, Wu X, Williams DR, et al. High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2. Proc Natl Acad Sci USA. 2010; 107: 7904–7909.
[23] Jackson AL, Burchard J, Schelter J, Chau BN, Cleary M, Lim L, et al. Widespread siRNA “off-target” transcript silencing mediated by seed region sequence complementarity. RNA. 2006; 12: 1179–1187.
[24] Seyfried TN, Huysentruyt LC. On the origin of cancer metastasis. Crit Rev Oncog. 2013; 18: 43–73.
[25] Yang Y, Zheng H, Zhan Y, Fan S. An emerging tumor invasion mechanism about the collective cell migration. Am J Transl Res. 2019; 11: 5301–5312.
[26] Nair NU, Das A, Rogkoti V-M, Fokkelman M, Marcotte R, de Jong CG, et al. Migration rather than proliferation transcriptomic signatures are strongly associated with breast cancer patient survival. Sci Rep. 2019; 9: 10989.
[27] Kojima S, Enokida H, Yoshino H, Itesako T, Chiyomaru T, Kinoshita T, et al. The tumor-suppressive microRNA-143/145 cluster inhibits cell migration and invasion by targeting GOLM1 in prostate cancer. J Hum Genet. 2013; 59: 78–87.
[28] Götte M, Mohr C, Koo CY, Stock C, Vaske AK, Viola M, et al. miR-145-dependent targeting of junctional adhesion molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness. Oncogene. 2010; 29: 6569–6580.
[29] El Gammal AT, Brüchmann M, Zustin J, Isbarn H, Hellwinkel OJC, Köllermann J, et al. Chromosome 8p deletions and 8q gains are associated with tumor progression and poor prognosis in prostate cancer. Clin Cancer Res. 2010; 16: 56–64.
[30] Mehrazin R, Dulaimi E, Uzzo RG, Devarjan K, Pei J, Smaldone MC, et al. The correlation between gain of chromosome 8q and survival in patients with clear and papillary renal cell carcinoma. Ther Adv Urol. 2018; 10: 3–10.
[31] Wang M, Ren D, Guo W, Wang Z, Huang S, Du H, et al. Loss of miR-100 enhances migration, invasion, epithelial-mesenchymal transition and stemness properties in prostate cancer cells through targeting Argonaute 2. Int J Oncol. 2014; 45: 362–372.
[32] Cheng N, Li Y, Han Z-G. Argonaute2 promotes tumor metastasis by way of up-regulating focal adhesion kinase expression in hepatocellular carcinoma. Hepatology. 2013; 57: 1906–1918.
[33] Zhang Y, Wang B, Chen X, Li W, Dong P. AGO2 involves the malignant phenotypes and FAK/PI3K/AKT signaling pathway in hypopharyngeal-derived FaDu cells. Oncotarget. 2017; 8: 54735–54746.
[34] Völler D, Reinders J, Meister G, Bosserhoff AK. Strong reduction of AGO2 expression in melanoma and cellular consequences. Br J Cancer. 2013; 109: 3116–3124.
[35] Huang W, Huang F, Lei Z, Luo H. LncRNA SNHG11 Promotes Proliferation, Migration, Apoptosis, and Autophagy by Regulating hsa-miR-184/AGO2 in HCC. Onco Targets Ther. 2020; 13: 413–421.
[36] Huttenlocher A, Sandborg RR, Horwitz AF. Adhesion in cell migration. Curr Opin Cell Biol. 1995; 7: 697–706.
[37] Adams BD, Claffey KP, White BA. Argonaute-2 expression is regulated by epidermal growth factor receptor and mitogen-activated protein kinase signaling and correlates with a transformed phenotype in breast cancer cells. Endocrinology. 2009; 150: 14–23.
[38] Voss G, Haflidadóttir BS, Järemo H, Persson M, Catela Ivkovic T, Wikström P, et al. Regulation of cell-cell adhesion in prostate cancer cells by microRNA-96 through upregulation of E-Cadherin and EpCAM. Carcinogenesis. 2020; 41: 865–874.
Cite This Article
  • APA Style

    Sujin Kim, Yoonseo Kim, Wonse Kim, Woo Rin Lee. (2020). Effect of AGO2 Depletion on Cell Migration of A172 Brain Cancer Cell. Cancer Research Journal, 8(3), 51-56. https://doi.org/10.11648/j.crj.20200803.12

    Copy | Download

    ACS Style

    Sujin Kim; Yoonseo Kim; Wonse Kim; Woo Rin Lee. Effect of AGO2 Depletion on Cell Migration of A172 Brain Cancer Cell. Cancer Res. J. 2020, 8(3), 51-56. doi: 10.11648/j.crj.20200803.12

    Copy | Download

    AMA Style

    Sujin Kim, Yoonseo Kim, Wonse Kim, Woo Rin Lee. Effect of AGO2 Depletion on Cell Migration of A172 Brain Cancer Cell. Cancer Res J. 2020;8(3):51-56. doi: 10.11648/j.crj.20200803.12

    Copy | Download

  • @article{10.11648/j.crj.20200803.12,
      author = {Sujin Kim and Yoonseo Kim and Wonse Kim and Woo Rin Lee},
      title = {Effect of AGO2 Depletion on Cell Migration of A172 Brain Cancer Cell},
      journal = {Cancer Research Journal},
      volume = {8},
      number = {3},
      pages = {51-56},
      doi = {10.11648/j.crj.20200803.12},
      url = {https://doi.org/10.11648/j.crj.20200803.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20200803.12},
      abstract = {AGO2, a protein-coding and miRNA regulating gene, has recently been identified as a phenomenal biomarker in cancer development research. Its role varies in different cancers, acting as either a tumor suppressor or an oncogene. However, no research has been conducted on the correlation between AGO2 and brain cancer yet. The aim of this study was to define the association of AGO2 amplification and brain cancer patient’s survival and to investigate the functional role of AGO2 in brain cancer cell migration. 20 brain cancer studies with a total of 6164 patient samples via cBioPortal were analyzed. After the patients were divided into two groups: AGO2 amplified group and AGO2 non-amplified group, the overall patients’ survival rate was analyzed by Kaplan-Meier. The positive correlation between the AGO2 amplified group and survival rates was discovered. To find out how AGO2 amplification increased patients’ survival rates, we performed an in vitro assay to silence AGO2 expression using two siRNAs targeting AGO2 in A172 brain cancer cell line. The wound-healing assay was performed to show that both siRNAs targeting AGO2 promoted cell migration of A172. Therefore, AGO2 may function as a tumor suppressor and enhances survival rates of brain cancer patients by inhibiting cancer cell migration. Further investigation of the mechanisms affecting AGO2 dysregulation will provide insights into the molecular differences underpinning brain cancer patient’s survival rate.},
     year = {2020}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Effect of AGO2 Depletion on Cell Migration of A172 Brain Cancer Cell
    AU  - Sujin Kim
    AU  - Yoonseo Kim
    AU  - Wonse Kim
    AU  - Woo Rin Lee
    Y1  - 2020/10/16
    PY  - 2020
    N1  - https://doi.org/10.11648/j.crj.20200803.12
    DO  - 10.11648/j.crj.20200803.12
    T2  - Cancer Research Journal
    JF  - Cancer Research Journal
    JO  - Cancer Research Journal
    SP  - 51
    EP  - 56
    PB  - Science Publishing Group
    SN  - 2330-8214
    UR  - https://doi.org/10.11648/j.crj.20200803.12
    AB  - AGO2, a protein-coding and miRNA regulating gene, has recently been identified as a phenomenal biomarker in cancer development research. Its role varies in different cancers, acting as either a tumor suppressor or an oncogene. However, no research has been conducted on the correlation between AGO2 and brain cancer yet. The aim of this study was to define the association of AGO2 amplification and brain cancer patient’s survival and to investigate the functional role of AGO2 in brain cancer cell migration. 20 brain cancer studies with a total of 6164 patient samples via cBioPortal were analyzed. After the patients were divided into two groups: AGO2 amplified group and AGO2 non-amplified group, the overall patients’ survival rate was analyzed by Kaplan-Meier. The positive correlation between the AGO2 amplified group and survival rates was discovered. To find out how AGO2 amplification increased patients’ survival rates, we performed an in vitro assay to silence AGO2 expression using two siRNAs targeting AGO2 in A172 brain cancer cell line. The wound-healing assay was performed to show that both siRNAs targeting AGO2 promoted cell migration of A172. Therefore, AGO2 may function as a tumor suppressor and enhances survival rates of brain cancer patients by inhibiting cancer cell migration. Further investigation of the mechanisms affecting AGO2 dysregulation will provide insights into the molecular differences underpinning brain cancer patient’s survival rate.
    VL  - 8
    IS  - 3
    ER  - 

    Copy | Download

Author Information
  • Loomis Chaffee School, Connecticut, United States

  • Saint Stephen's Episcopal School, Texas, United States

  • Saint Paul's School, New Hampshire, United States

  • Department Biological Science, University of Suwon, Hwaseong, Republic of Korea

  • Sections