A novel regulatory mechanism of TGF-beta pathway via long non-coding RNA

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H04696
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Kitagawa Masatoshi 浜松医科大学, 医学部, 教授 (50294971)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: TGF-beta / 長鎖ncRNA / がん細胞 / 上皮間葉転換

Outline of Final Research Achievements

We identified a novel lncRNA ELIT-1 (EMT-associated lncRNA induced by TGFbeta-1) involved in TGFbeta-signaling. ELIT-1 is transcriptionally and rapidly induced via TGFbeta-Smad-pathway and promotes EMT and cell migration via expression of EMT-associated genes such as Snail and N-cadherin. A positive correlation between high expression of ELIT-1 and poor prognosis in lung adenocarcinoma cancer patients. ELIT-1 bound to Smad3 but not Smad2 and facilitated recruitment of Smad3 to promoter regions of the target genes. These results suggest that ELIT-1 binds to Smad3 and recruits to the Smad3-target genes such as Snail as a novel mediator of TGFbeta-Smad pathway and thereby it is involved in promotion of EMT.

Free Research Field

分子生物学、腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

我々が見出した新規lncRNA ELIT-1は、Smad3と結合することによりvimentin、Snail等の上皮間葉転換(EMT)関連遺伝子の発現制御に関与して、EMTの誘導を正に制御して浸潤能の増強に関与する。さらにELIT-1の高発現は肺腺がんの予後不良と相関することも判明した。よってELIT-1はがんの予後マーカーとなる可能性がある。さらにELIT-1の発現や機能の阻害する化合物はがん転移抑制薬となる可能性がある。