TRF/miR-1280 suppresses stem cell-like cells and metastasis in colorectal cancer

Bingqing Huang, Huipeng Yang, Xixi Cheng, Dan Wang, Shuyu Fu, Wencui Shen, Qi Zhang, Lijuan Zhang, Zhenyi Xue, Yan Li, Yurong Da, Qing Yang, Zesong Li, Li Liu, Liang Qiao, Ying Kong, Zhi Yao, Peng Zhao, Min Li, Rongxin Zhang

Research output: Contribution to journalArticle

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3194-3206
Number of pages13
JournalCancer Research
Volume77
Issue number12
DOIs
StatePublished - Jun 15 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Huang, B., Yang, H., Cheng, X., Wang, D., Fu, S., Shen, W., Zhang, Q., Zhang, L., Xue, Z., Li, Y., Da, Y., Yang, Q., Li, Z., Liu, L., Qiao, L., Kong, Y., Yao, Z., Zhao, P., Li, M., & Zhang, R. (2017). TRF/miR-1280 suppresses stem cell-like cells and metastasis in colorectal cancer. Cancer Research, 77(12), 3194-3206. https://doi.org/10.1158/0008-5472.CAN-16-3146