PITX1 inhbits melanoma proliferation by regulation of SOX10 transcription

• Project/Area Number: 18K16030
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Tottori University
• Principal Investigator: OHIRA Takahito 鳥取大学, 医学部, 助教 (60757665)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: メラノーマ / がん遺伝子 / がん抑制遺伝子 / 腫瘍生物学 / 薬剤耐性 / PITX1 / ChIP-seq / BRAF

Outline of Final Research Achievements

Melanoma is one of the most aggressive types of cancer in which resistance to treatments. Therefore, it is important to discover novel molecular targets of melanoma progression as potential treatments. Here we show that paired-like homeodomain transcription factor 1 (PITX1) plays a crucial role in the inhibition of melanoma progression thorough regulation of SRY-box transcription factors (SOX) gene family mRNA transcription.
The findings in this study indicate that PITX1 may act as a negative regulatory factor in the development and progression of melanoma via direct targeting of the SOX signaling pathway.

Academic Significance and Societal Importance of the Research Achievements

本研究では、がん抑制遺伝子であるPITX1の詳細な機能解析を通して、メラノーマにおける新規のがん抑制シグナル伝達経路の存在を明らかにした。具体的には、メラノーマのドライバー遺伝子(発がんのカギとなるがん遺伝子)として知られるSOX10遺伝子の発現を、PITX1はSOX9遺伝子を介して抑制することを見出した。したがって、本研究成果はメラノーマの発がん機構におけるその分子機序の新規知見を与えるだけでなく、同時に新たな分子標的薬の開発に向けた糸口になることが期待される。

Research Products

• [Journal Article] A novel Xist RNA-mediated chromosome inactivation model using a mouse artificial chromosome (2020)
  • Author(s): Inaoka, D. Sunamura, N. Ohira, T. Nakayama, Y. Kugoh, H.
  • Journal Title: Biotechnology letters Volume: 42 Issue: 5 Pages: 697-705
  • DOI: 10.1007/s10529-020-02826-z
  • Peer Reviewed / Open Access
• [Journal Article] An efficient protein production system via gene amplification on a human artificial chromosome and the chromosome transfer to CHO cells. (2019)
  • Author(s): Ohira T, Miyauchi K, Uno N, Shimizu N, Kazuki Y, Oshimura M, Kugoh H.
  • Journal Title: Scientific Reports Volume: 18 Issue: 1
  • DOI: 10.1038/s41598-019-53116-2
  • Peer Reviewed / Open Access
• [Journal Article] PITX1 protein interacts with ZCCHC10 to regulate hTERT mRNA transcription. (2019)
  • Author(s): Ohira T, Kojima H, Kuroda Y, Aoki S, Inaoka D, Osaki M, Wanibuchi H, Okada F, Oshimura M, Kugoh H.
  • Journal Title: Plos one Volume: 12 Issue: 8 Pages: e0217605-e0217605
  • DOI: 10.1371/journal.pone.0217605
  • Peer Reviewed / Open Access
• [Journal Article] Possible Relationship Between <i>MYBL1</i> Alterations and Specific Primary Sites in Adenoid Cystic Carcinoma: A Clinicopathological and Molecular Study of 36 Cases (2019)
  • Author(s): Endo Yukari、Kuwamoto Satoshi、Ohira Takahito、Matsushita Michiko、Matsushige Takahiro、Fukuhara Takahiro、Nakamoto Shu、Hayashi Kazuhiko、Kugoh Hiroyuki、Hirooka Yasuaki
  • Journal Title: Yonago Acta Medica Volume: 62 Issue: 1 Pages: 067-076
  • DOI: 10.33160/yam.2019.03.010
  • NAID: 130007626300
  • ISSN: 0513-5710, 1346-8049
  • Peer Reviewed
• [Presentation] PITX1 is a novel suppressor of SOX10 and inhibit melanoma growth. (2020)
  • Author(s): T. Ohira, H. Kugoh.
  • Organizer: 第79回 日本癌学会学術総会
• [Presentation] An efficient protein production system via gene amplification on a human artificial chromosome and the chromosome transfer to CHO cells. (2019)
  • Author(s): T. Ohira, K. Miyauchi, N. UNO, N. Shimizu, K. Kazuki, M. Oshimura, H. Kugoh.
  • Organizer: 第41回 日本分子生物学会年会
• [Presentation] X染色体不活化機構解明に向けた人工染色体の活用 (2018)
  • Author(s): 稲岡大悟, 大平崇人,押村光雄, 中山祐二, 久郷裕之
  • Organizer: 第41回日本分子生物学会
• [Remarks] 鳥取大学 医学部 生命科学科細胞ゲノム機能学 HP
  • URL: https://saiboukougaku.jimdo.c
• [Remarks] 研究室 ホームページ
  • URL: https://saiboukougaku.jimdofree.com/
• [Remarks] 研究室 ホームページ
  • URL: https://saiboukougaku.jimdo.com/