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Cancer Res. 2017 Jun 15;77(12):3194-3206. doi: 10.1158/0008-5472.CAN-16-3146. Epub 2017 Apr 26.

tRF/miR-1280 Suppresses Stem Cell-like Cells and Metastasis in Colorectal Cancer.

Author information

1
Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China.
2
Department of Pathology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
3
Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Vision Science, Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China.
4
Department of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
5
Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
6
Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China.
7
Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, Texas.
8
Storr Liver Centre, Westmead Millennium Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia.
9
Department of Biochemistry and Molecular Biology, Liaoning Key Lab of Glycobiology and Glycoengn, Dalian Medical University, Dalian, China.
10
Department of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China. rxzhang@tmu.edu.cn 13752085215@163.com kongying@dmu.edu.cn.
11
Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
12
Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
13
Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China. rxzhang@tmu.edu.cn 13752085215@163.com kongying@dmu.edu.cn.
14
Laboratory of Immunology and Inflammation, Guangdong Pharmaceutical University, Guangzhou, China.

Abstract

Several studies have shown that tRNAs can be enzymatically cleaved to generate distinct classes of tRNA-derived fragments (tRF). Here, we report that tRF/miR-1280, a 17-bp fragment derived from tRNALeu and pre-miRNA, influences Notch signaling pathways that support the function of cancer stem-like cells (CSC) in colorectal cancer progression. tRF/miR-1280 expression was decreased in human specimens of colorectal cancer. Ectopic expression of tRF/miR-1280 reduced cell proliferation and colony formation, whereas its suppression reversed these effects. Mechanistic investigations implicated the Notch ligand JAG2 as a direct target of tRF/miR-1280 binding through which it reduced tumor formation and metastasis. Notably, tRF/miR-1280-mediated inactivation of Notch signaling suppressed CSC phenotypes, including by direct transcriptional repression of the Gata1/3 and miR-200b genes. These results were consistent with findings of decreased levels of miR-200b and elevated levels of JAG2, Gata1, Gata3, Zeb1, and Suz12 in colorectal cancer tissue specimens. Taken together, our results established that tRF/miR-1280 suppresses colorectal cancer growth and metastasis by repressing Notch signaling pathways that support CSC phenotypes. Furthermore, they provide evidence that functionally active miRNA can be derived from tRNA, offering potential biomarker and therapeutic uses. Cancer Res; 77(12); 3194-206. ©2017 AACR.

PMID:
28446464
DOI:
10.1158/0008-5472.CAN-16-3146
[Indexed for MEDLINE]
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