Examination of the mechanisms by which SOX2 promotes cell proliferation in esophageal cancer

• Project/Area Number: 15K19040
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human genetics
• Research Institution: Tokyo Medical and Dental University (2016-2017); Kyoto Prefectural University of Medicine (2015)
• Principal Investigator: GEN Yasuyuki 東京医科歯科大学, 難治疾患研究所, 助教 (80596156)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: SOX2 / esophageal cancer / miRNA / 食道扁平上皮癌 / PTEN

Outline of Final Research Achievements

Our previous study revealed that the SOX2 gene is frequently amplified and overexpressed in esophageal squamous cell carcinoma (ESCC), and that SOX2 promotes ESCC cell proliferation in vitro and in vivo via upreguation of AKT/mTOR signaling pathway. In the present study, we showed that SOX2 increased the expression of miR-19a-3p indirectly. miR-19a-3p upregulated AKT signaling pathway by repressing PTEN, a negative regulator of AKT. Furthermore, we showed that AKT/mTOR dual inhibitor suppressed the proliferation of SOX2-amplifed ESCC cells.

Research Products

• [Journal Article] miR-3140 suppresses tumor cell growth by targeting BRD4 via its coding sequence and downregulates the BRD4-NUT fusion oncoprotein (2018)
  • Author(s): Tonouchi Erina、Gen Yasuyuki、Muramatsu Tomoki、Hiramoto Hidekazu、Tanimoto Kousuke、Inoue Jun、Inazawa Johji
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 4482-4482
  • DOI: 10.1038/s41598-018-22767-y
  • Peer Reviewed / Open Access
• [Journal Article] Loss of PAR-3 protein expression is associated with invasion, lymph node metastasis, and poor survival in esophageal squamous cell carcinoma. (2017)
  • Author(s): Kitaichi T, Yasui K, Gen Y, Dohi O, Iwai N, Tomie A, Yamada N, Terasaki K, Umemura A, Nishikawa T, Yamaguchi K, Moriguchi M, Sumida Y, Mitsuyoshi H, Naito Y, Zen Y, Itoh Y.
  • Journal Title: Hum Pathol Volume: 62 Pages: 134-140
  • DOI: 10.1016/j.humpath.2017.01.009
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] p62, Upregulated during Preneoplasia, Induces Hepatocellular Carcinogenesis by Maintaining Survival of Stressed HCC-Initiating Cells. (2016)
  • Author(s): Umemura A, He F, Taniguchi K, Nakagawa H, Yamachika S, Font-Burgada J, Zhong Z, Subramaniam S, Raghunandan S, Duran A, Linares JF, Reina-Campos M, Umemura S, Valasek MA, Seki E, Yamaguchi K, Koike K, Itoh Y, Diaz-Meco MT, Moscat J, Karin M.
  • Journal Title: Cancer Cell Volume: 29 Pages: 935-948
  • DOI: 10.1016/j.canlet.2017.04.002
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] The exploration of miRNAs that induce cell death in p53 inactive cancer cells using functional-miRNA screening (2017)
  • Author(s): Yasuyuki Gen, Jun Inoue1, Johji Inazawa,
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 機能的miRNAスクリーニングを用いたp53不活性型癌に細胞死を誘 導するmiRNAの探索 (2017)
  • Author(s): 玄泰行、井上純、稲澤譲治
  • Organizer: 日本人類遺伝学会第62回大会
• [Patent(Industrial Property Rights)] マイクロRNA及びその誘導体を有効成分とするがん治療剤 (2017)
  • Inventor(s): 稲澤譲治、玄泰行、村松智輝、外内えり奈
  • Industrial Property Rights Holder: 稲澤譲治、玄泰行、村松智輝、外内えり奈
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-229046
  • Filing Date: 2017