An RNA binding protein, RBM5 modulates chemotherapeutic efficacy via the expression of p62.

• Project/Area Number: 24590910
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hokkaido University
• Principal Investigator: SHIMIZU Yuich 北海道大学, 医学(系)研究科(研究院), 准教授 (90333608)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Takahiko 北海道大学, 大学院医学研究科, 客員研究員 (80333607)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 薬剤耐性 / 抗癌剤耐性

Outline of Final Research Achievements

The molecular mechanisms of drug resistance against cancer chemotherapy have not been yet fully elucidated. Several studies have shown that the acquisition of drug resistance is tightly regulated by post-transcriptional regulators such as RNA binding proteins, which change the stability and translation of mRNAs encoding factors involved in drug metabolism. RBM5 (RNA-binding motif protein 5) is known to modulate apoptosis and cell cycle arrest but the molecular mechanisms of RBM5 function remains to be examined. We show here that RBM5 modulates the expression of p62, which is a scaffold protein that has multiple functions, such as cell survival, oxidative stress response, and autophagy. Recent reports suggest that autophagy is one of the processes contributing to drug resistance. We suggest that RBM5 plays important roles in the post-transcriptional regulation of mRNAs that are involved in the chemotherapeutic cellular response.

Research Products

• [Journal Article] Human intestinal spirochetosis is significantly associated with sessile serrated adenomas/polyps. (2014)
  • Author(s): Omori S, Mabe K, Hatanaka K, Ono M, Matsumoto M, Takahashi M, Yoshida T, Ono S, Shimizu Y, Sugai N, Suzuki A, Katsuki S, Fujii T, Kato M, Asaka M, Sakamoto N
  • Journal Title: Pathol Res Pract. Volume: 210 Issue: 7 Pages: 440-443
  • DOI: 10.1016/j.prp.2014.03.007
  • NAID: 120005462415
• [Journal Article] Endoscopic in vivo cellular imaging of superficial squamous cell carcinoma of the head and neck by using an integrated endocytoscopy system. (2013)
  • Author(s): Shimizu Y, Takahashi M, Yoshida T, Ono S, Mabe K, Kato M, Asaka M, Hatanaka K, Sakamoto N.
  • Journal Title: Gastrointest Endosc Volume: 78 Issue: 2 Pages: 351-358
  • DOI: 10.1016/j.gie.2013.03.1336
  • Peer Reviewed
• [Journal Article] What is an adequate management strategy for pharyngeal low-grade dysplasia? (2013)
  • Author(s): Shimizu Y, Takahashi M, Yoshida T, Ono S, Mabe K, Kato M, Asaka M, Sakamoto N.
  • Journal Title: Gastrointest Endosc Volume: 77 Issue: 6 Pages: 972-973
  • DOI: 10.1016/j.gie.2012.12.012
  • Peer Reviewed
• [Journal Article] Identification of a high risk gastric cancer group using serum pepsinogen after successful eradication of Helicobacter pylori. (2013)
  • Author(s): Haneda M, Kato M, Ishigaki S, Suzuki M, Takahashi M, Nakagawa M, Ono S, Mori Y, Mabe K, Kudo T, Nakagawa S, Shimizu Y, Asaka M.
  • Journal Title: J Gastroenterol Hepatol. Volume: 28 Issue: 1 Pages: 78-83
  • DOI: 10.1111/j.1440-1746.2012.07285.x
  • Peer Reviewed