한빛사논문
- 조회464
Ji Hoon Lee1,†, Juyeong Hong1,†, Zhao Zhang1,†, Bárbara de la Peña Avalos2,3, Cecilia J. Proietti4, Agustina Roldán Deamicis4, Pablo Guzmán G.5, Hung-Ming Lam6, Jose Garcia6, Martine P. Roudier6, Anthony E. Sisk7, Richard De La Rosa1, Kevin Vu8, Mei Yang1, Yiji Liao1, Jessica Scheirer1, Douglas Pechacek1, Pooja Yadav9,10, Manjeet K. Rao9,10, Siyuan Zheng10,11, Teresa L. Johnson-Pais12, Robin J. Leach3,9, Patricia V. Elizalde4, Eloïse Dray2,3 and Kexin Xu1,*
1Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
2Department of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
3Mays Cancer Center, UT Health San Antonio MD Anderson, San Antonio, TX 78229, USA.
4Laboratory of Molecular Mechanisms of Carcinogenesis and Molecular Endocrinology, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires C1428ADN, Argentina.
5Departamento de Anatomía Patológica (BIOREN), Universidad de La Frontera, Temuco Casilla 54-D, Chile.
6Department of Urology, University of Washington, Seattle, WA 98195, USA.
7Department of Pathology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
8Department of Medical Education, Joe R. and Teresa Lozano Long School of Medicine, San Antonio, TX 78229, USA.
9Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
10Greehey Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
11Department of Population Health Sciences, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
12Department of Urology, University of Texas Health Sciences Center at San Antonio, San Antonio, TX 78229, USA.
*Corresponding author.
†These authors contributed equally to this work.
Abstract
The role of RNA methylation on N6-adenosine (m6A) in cancer has been acknowledged, but the underlying mechanisms remain obscure. Here, we identified homeobox containing 1 (HMBOX1) as an authentic target mRNA of m6A machinery, which is highly methylated in malignant cells compared to the normal counterparts and subject to expedited degradation upon the modification. m6A-mediated down-regulation of HMBOX1 causes telomere dysfunction and inactivation of p53 signaling, which leads to chromosome abnormalities and aggressive phenotypes. CRISPR-based, m6A-editing tools further prove that the methyl groups on HMBOX1 per se contribute to the generation of altered cancer genome. In multiple types of human cancers, expression of the RNA methyltransferase METTL3 is negatively correlated with the telomere length but favorably with fractions of altered cancer genome, whereas HMBOX1 mRNA levels show the opposite patterns. Our work suggests that the cancer-driving genomic alterations may potentially be fixed by rectifying particular epitranscriptomic program.
논문정보
- Research article
- 2021년 07월 (BRIC 등록일 2021-08-04)
- 국외 연구진
- 생명과학 > 분자생물학
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