Novel anticancer agents targeting tumor-promoting non-coding RNA

2012 Fiscal Year Final Research Report

• Project/Area Number: 23650599
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: The University of Tokushima
• Principal Investigator: KONDO Shigetada 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 特任助教 (40304513)
• Project Period (FY): 2011 – 2012
• Keywords: ノンゴーディングRNA / 悪性腫瘍

Research Abstract

I have investigated the direct effects of antiangiogenic agents on tumor cells, and revealed that treatment of cancer cells with vascular endothelial growth factor (VEGF)-targeting agents, including avastin and VEGF receptor multi kinase inhibitor, induced novel protein-non-coding RNAs. Overexpression of these non-coding RNAs made tumor cells resistant to anticancer drug- and hypoxia-induced apoptosis. In this research project, I developed two efficient siRNAs targeting novel tumor-promoting non-conding RNAs (ncRNAs). I evaluated efficacy ofthose siRNA on tumor cells and xenograft tumors. Knockdown of ncRNAs increased apoptosis of tumor cells by cytotoxic anticancer drugs (5-FU, cisplatin, etoposide). Furthermore, knockdown of ncRNAs in xenograft tumors enhanced antitumor effects of those cytotoxic anticancer agnets.

Research Products

• [Journal Article] Chronic inhibition of tumor cell-derived VEGF enhances the malignant phenotype of colorectal cancer cells (2013)
  • Author(s): Yamagishi, N., Teshima-Kondo, S. (corresponding author), Masuda, K., Nishida, K., Kuwano, Y., Dang, D.DDang, L.H., Nikawa, T., and Rokutan, K
  • Journal Title: BMC Cancer Volume: 13 Pages: 229
  • DOI: doi: 10.1186/1471-2407-13-229
  • Peer Reviewed
• [Journal Article] Soy Glycinin Contains a Functional Inhibitory Sequence against Muscle-Atrophy-Associated Ubiquitin Ligase Cbl-b (2013)
  • Author(s): Abe T, Kohno S, Yama T, Ochi A, Suto T, Hirasaka K, Ohno A, Teshima-Kondo S, Okumura Y, Oarada M, Choi I, Mukai R, Terao J, Nikawa T
  • Journal Title: Int J Endocrinol Volume: 907565 (2013)
  • DOI: doi:10.1155/2013/907565
  • Peer Reviewed
• [Journal Article] Cbl-b Is a Critical Regulator of Macrophage Activation Associated with Obesity-Induced Insulin Resistance in Mice (2013)
  • Author(s): Abe T, Hirasaka K, Kagawa S, Kohno S, Ochi A, Utsunomiya K, Sakai A, Ohno A, Teshima-Kondo S, Okumura Y, Oarada M, Maekawa Y, Terao J, Mills EM, Nikawa T
  • Journal Title: Diabetes Volume: 62(6) Pages: 1957-69
  • DOI: doi:10.2337/db12-0677
  • Peer Reviewed
• [Journal Article] An Intracellular Fragment of Osteoactivin Formed by Ectodomain Shedding Translocated to the Nucleoplasm and Bound to RNA Binding Proteins (2012)
  • Author(s): Utsunomiya K, Owaki K, Okumura Y, Yano M, Oto T, Suzuki E, Tamura S, Abe T, Kohno S, Ohno A, Hirasaka K, Teshima-Kondoh S, Nikawa T
  • Journal Title: Biosci Biotechnol Biochem Volume: 76(12) Pages: 2225-2229
  • Peer Reviewed
• [Journal Article] Unloading stress disturbs muscle regeneration through perturbed recruitment and function of macrophages (2012)
  • Author(s): Kohno S, Yamashita Y, Abe T, Hirasaka K, Oarada M, Ohno A, Teshima-Kondo S, Higashibata A, Choi I, Mills EM, Okumura Y, Terao J, Nikawa T
  • Journal Title: J Appl Physiol Volume: 112(10) Pages: 1773-82
  • DOI: doi:10.1152/japplphysiol.00103.2012
  • Peer Reviewed
• [Presentation] 新規腫瘍促進性ノンコーディングRNAの発現制御 (2012)
  • Author(s): 近藤茂忠,山岸直子
  • Organizer: 第71回日本癌学会学術集会
  • Place of Presentation: ロイトン札幌(北海道)
  • Year and Date: 2012-09-20
• [Presentation] Vegf遺伝子にコードされた新規腫瘍促進性ノンコーディングRNAの機能解析 (2012)
  • Author(s): 山岸直子、近藤茂忠
  • Organizer: 第71回日本癌学会学術集会
  • Place of Presentation: ロイトン札幌(北海道)
  • Year and Date: 2012-09-20
• [Presentation] Identification of a novel tumor promoting non-coding RNA encoded in the Vegf gene (2011)
  • Author(s): 近藤茂忠, 山岸直子
  • Organizer: Cell Symposia: Regulatory RNAs
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2011-10-11