A domestic research team verified the action mechanism of a protein ’embryonic stem cell transcription factor (LIN28A),’ which is known to regulate the growth and differentiation of stem cells and also to play part in cancer cells. The research outcome is anticipated to serve as a new mark for the treatment of intractable and incurable diseases using stem cells and for the development of carcinogenic substances in the future.
A research team led by Professor Lee Dae-yeop and Professor Han Yong-man from the Dept. of Biological Sciences at the Korea Advanced Institute of Science and Technology of announced on the 7th that LIN28A protein methylated with ‘Cyston methylase (SET7/9)’ suppresses stem cell differentiation by obstructing the growth regulating RNAs.
LIN28 is a protein used in the production of induced pluripotent stem cells (iPSC) and the pluripotency of stem cells. Although it is known to take part in the regulation of various cancer cells, not many studies have been conducted on the detailed regulatory mechanism of LIN28.
The research team verified a new molecular mechanism of LIN 28A to ‘TUTase-independently’ suppress the maturation process of growth regulatory RNA through methylation within the cell nucleus in addition to the mechanism to ‘TUTase-dependently’ suppress maturation process of growth regulatory RNA in the cytoplasm, which had already been verified. Through this performance, the team demonstrated that LIN28A maintains pluripotency in stem cells and suppresses the cell differentiation.
A member of the research team said, “This research outcome holds great importance as it enabled us to secure a technology for wide application even to the clinical stage, such as the treatment of intractable and incurable diseases as well as cancer treatment and iPSC production in addition to embryonic stem cells.”
The research outcome was published in the ‘Cell Stem Cell,’ which is an international scientific journal for stem cell fields, on the 4th.
Kwon Geon-ho | wingh1@etnews.com
줄기세포 성장 조절 핵심 인자 기능 규명
국내 연구진이 줄기세포 성장과 분화를 조절하고, 암세포에도 관여하는 것으로 알려진 단백질 ‘배아줄기세포전사인자(LIN28A)’의 작용 메커니즘을 밝혔다. 향후 줄기세포를 통한 불치병과 난치병 치료, 항암물질 개발의 새로운 표적이 될 것으로 기대된다.
한국과학기술원 생명과학과 이대엽?한용만 교수팀은 ‘시스톤메틸화효소(SET7/9)’에 의해 메틸화된 LIN28A 단백질이 성장조절 RNA 생성을 방해해 줄기세포 분화를 억제한다고 7일 밝혔다.
LIN28은 줄기세포 전분화능과 유도만능줄기세포(iPSC) 생산에 사용되는 단백질이며, 여러 암세포의 조절과정에도 관여하는 단백질이라고 알려졌지만 구체적인 조절 기전은 많이 연구되지 않았다.
연구팀은 LIN28A가 세포질에서 ‘텃효소(TUTase)-의존적’으로 성장조절 RNA 성숙과정을 저해하는 기존에 알려진 기전 외에도, 핵 내에서 메틸화에 의해 ‘텃효소-비의존적’으로 성장조절 RNA 성숙과정을 저해한다는 분자적 기전을 새롭게 규명했다. 이를 통해 실제 줄기세포에서 전분화능을 유지하고 분화를 저해하는 사실을 입증했다.
연구팀은 “배아줄기세포 뿐만 아니라 유도만능줄기세포와 암치료, 난치병과 불치병 치료 등 임상단계까지 폭넓게 확장될 수 있는 기술을 확보한 것에서 중요한 의의를 지닌다”고 말했다.
연구결과는 줄기세포 분야 국제학술지 ‘셀 스템셀(Cell Stem Cell)’ 4일자에 게재됐다
권건호기자 | wingh1@etnews.com