Downregulation o fserine/arginine-rich splicing factor 3 induces G1 cell cycle arrest and apoptosis in colon cancer cells

• Project/Area Number: 23590943
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kobe Pharmaceutical University (2012-2013); Kobe University (2011)
• Principal Investigator: TANAHASHI Toshihito 神戸薬科大学, 薬学部, 准教授 (30380067)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
• Keywords: 選択的スプライシング / RNA結合タンパク質 / 大腸がん / マイクロアレイ / ＲＮＡ結合タンパク質 / 細胞周期 / アポトーシス / p53 / RIP-Chip / 大腸癌

Research Abstract

Serine/arginine-rich splicing factor 3 (SRSF3) is a member of the SRSF family that plays wide-ranging roles in gene expression. SRSF3 knockdown induced G1 arrest and apoptosis in colon cancer cells (HCT116). Pathway analysis of differentially expressed transcripts in SRSF3-silenced cells and mRNAs immunoprecipitated with overexpressed SRSF3 suggested that SRSF3 preferentially associated with G1/S checkpoint regulator mRNAs and regulated their expression. SRSF3 knockdown decreased mRNA and protein levels of cyclins (D1, D3, and E1), E2F1, and E2F7. SRSF3 knockdown caused skipping of 81 nucleotides of the hipk2 exon 8. Resultant HIPK2 isoform partially lacking the E3 ubiquitin ligase-binding site became resistant to proteasome digestion. Predominant expression of the splice variant by selective decomposition of full-length hipk2 mRNA as well as by SERF3 knockdown induced apoptosis in a variety of colon cancer cells expressing wild-type or mutated p53.

Research Products

• [Journal Article] Downregulation of serine/arginine-rich splicing factor 3 induces G1 cell cycle arrest and apoptosis in colon cancer cells. (2014)
  • Author(s): Kurokawa K, Akaike Y, Masuda K, Kuwano Y, Nishida K, Yamagishi N, Kajita K, Tanahashi T, Rokutan K.
  • Journal Title: Oncogene. Volume: 33 Issue: 11 Pages: 1407-17
  • DOI: 10.1038/onc.2013.86
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of miR-19b and its target mRNAs in 5-fluorouracil resistance in colon cancer cells (2012)
  • Author(s): Kurokawa K, Tanahashi T, Iima T, Yamamoto Y, Akaike Y, Nishida K, Masuda K, Kuwano Y, Murakami Y, Fukushima M, Rokutan K
  • Journal Title: J Gastroenterol Volume: 47(8) Pages: 883-95
  • NAID: 10031051201
• [Journal Article] Role of miR-19b and its target mRNAs in 5-fluorouracil resistance in colon cancer cells (2012)
  • Author(s): Kurokawa K, Tanahashi T, Iima T, Yamamoto Y, Akaike Y, Nishida K, Masuda K, Kuwano Y, Murakami Y, Fukushima M, Rokutan
  • Journal Title: J Gastroenterol Volume: 47 Issue: 8 Pages: 883-895
  • DOI: 10.1007/s00535-012-0547-6
  • NAID: 10031051201
  • Peer Reviewed
• [Presentation] 酸化ストレスと選択的スプライシングのクロストーク (2011)
  • Author(s): 棚橋俊仁, 黒川憲, 六反一仁
  • Organizer: 日本消化器病学会第53回大会
  • Place of Presentation: 福岡国際センター、福岡
  • Year and Date: 2011-10-20
• [Presentation] Serine/arginine-rich splicing factor 3 (SRSF3) regulates G1/S checkpoint and p53-dependent apoptosis (2011)
  • Author(s): Kurokawa K, Akaike Y, Kajita K, Yamagishi N, Satake Y, Honda M, Nishida K, Kuwano Y, Masuda K, Tanahashi T, Rokutan K
  • Organizer: EMBO Meeting 2011
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2011-09-03
• [Presentation] 選択的スプライシング調節因子SRp20が制御する細胞周期とアポトーシス (2011)
  • Author(s): 黒川憲, 棚橋俊仁, 六反一仁
  • Organizer: 日本消化器病学会第97回総会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-13
• [Presentation] 酸化ストレスと選択的スプライシングのクロストーク (2011)
  • Author(s): 棚橋俊仁、黒川憲、六反一仁
  • Organizer: 日本消化器病学会第53回大会
  • Place of Presentation: 福岡国際センター（福岡）
• [Presentation] 選択的スプライシング調節因子SRp20が制御する細胞周期とアポトーシス (2011)
  • Author(s): 黒川憲、棚橋俊仁、六反一仁
  • Organizer: 日本消化器病学会第97回総会
  • Place of Presentation: 京王プラザホテル（東京）
• [Presentation] Serine/arginine-rich splicing factor 3 (SRSF3) regulates G1/S checkpoint and p53-dependent apoptosis (2011)
  • Author(s): Kurokawa K, Akaike Y, Kajita K, Yamagishi N, Satake Y, Honda M, Nishida K, Kuwano Y, Masuda K, Tanahashi T, Rokutan K
  • Organizer: 3rd EMBO Meeting
  • Place of Presentation: Vienna, Austria
• [Presentation] Premature stop codon-containing tra2beta4 mRNA isoform regulates cellular senescence (2011)
  • Author(s): Kajita K, Kuwano Y, Masuda K, Yamagishi N, Kurokawa K, Satake Y, Akaike Y, Honda M, Tanahashi T, Rokutan K
  • Organizer: 3rd EMBO Meeting
  • Place of Presentation: Vienna, Austria
• [Presentation] Transfomer-2beta regulates apoptosis through post-transcriptional regulation of bcl-2 (2011)
  • Author(s): Kuwano Y, Kajita K, Satake Y, Kurokawa K, Yamagishi N, Akaike Y, Honda M, Nishida K, Masuda K, Tanahashi T, Rokutan K
  • Organizer: Cell Symposia Regulatory RNAs
  • Place of Presentation: Chicago, USA
• [Presentation] Hu antigen R (huR) functions as an alternative pre-mRNA splicing enhancer of transformer 2-beta (Tra2beta) on exon definition under oxidative stress (2011)
  • Author(s): Masuda K, Yamagishi N, Kurokawa K, Satake Y, Kajita K, Akaike Y, Honda M, Nishida K, Kuwano Y, Tanahashi T, Rokutan K.
  • Organizer: Cell Symposia Regulatory RNAs
  • Place of Presentation: Chicago, USA
• [Presentation] The Mechanism of Transformer 2-βGene Expression in Response to Oxidative Stress in Human Colon Epithelial Cells (2010)
  • Author(s): Kuwano Y, Satake Y, Nishida K, Masuda K, Kurokawa K, Teshima-kondo S, Tanahashi T, Rokutan K
  • Organizer: 2010 Digestive Disease Week
  • Place of Presentation: New Orleans, LA, USA
• [Remarks]
  • URL: http://www.kobepharma-u.ac.jp/rsch/rsch_04r.html