| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Kirino, Yohei Loher, Phillipe Palazzo, Juan P. Suzuki, Ryusuke Honda, Shozo Imoto, Issei Rigoutsos, Isidore Shigematsu, Megumi |
| Description |
Author Affiliation: Honda S ( Computational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107); Loher P ( Computational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107); Shigematsu M ( Computational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107); Palazzo JP ( Department of Pathology, Anatomy, and Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107); Suzuki R ( Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048); Imoto I ( Department of Human Genetics, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8503, Japan.); Rigoutsos I ( Computational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107); Kirino Y ( Computational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107); |
| Abstract |
Sex hormones and their receptors play critical roles in the development and progression of the breast and prostate cancers. Here we report that a novel type of transfer RNA (tRNA)-derived small RNA, termed Sex HOrmone-dependent TRNA-derived RNAs (SHOT-RNAs), are specifically and abundantly expressed in estrogen receptor (ER)-positive breast cancer and androgen receptor (AR)-positive prostate cancer cell lines. SHOT-RNAs are not abundantly present in ER(-) breast cancer, AR(-) prostate cancer, or other examined cancer cell lines from other tissues. ER-dependent accumulation of SHOT-RNAs is not limited to a cell culture system, but it also occurs in luminal-type breast cancer patient tissues. SHOT-RNAs are produced from aminoacylated mature tRNAs by angiogenin-mediated anticodon cleavage, which is promoted by sex hormones and their receptors. Resultant 5'- and 3'-SHOT-RNAs, corresponding to 5'- and 3'-tRNA halves, bear a cyclic phosphate (cP) and an amino acid at the 3'-end, respectively. By devising a 'cP-RNA-seq' method that is able to exclusively amplify and sequence cP-containing RNAs, we identified the complete repertoire of 5'-SHOT-RNAs. Furthermore, 5'-SHOT-RNA, but not 3'-SHOT-RNA, has significant functional involvement in cell proliferation. These results have unveiled a novel tRNA-engaged pathway in tumorigenesis of hormone-dependent cancers and implicate SHOT-RNAs as potential candidates for biomarkers and therapeutic targets. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
29 |
| Volume Number |
112 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2015-07-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Breast Neoplasms Metabolism Pathology Gonadal Steroid Hormones Prostatic Neoplasms RNA, Transfer Amino Acids Animals Bombyx Cell Line, Tumor Cell Proliferation Epithelial Cells Gene Knockdown Techniques Hydroxylation Models, Biological Molecular Sequence Data Phosphates Chemistry Genetics Real-Time Polymerase Chain Reaction Receptors, Androgen Receptors, Estrogen Ribonuclease, Pancreatic Sequence Analysis, RNA Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
