TY - JOUR
T1 - TRF/miR-1280 suppresses stem cell-like cells and metastasis in colorectal cancer
AU - Huang, Bingqing
AU - Yang, Huipeng
AU - Cheng, Xixi
AU - Wang, Dan
AU - Fu, Shuyu
AU - Shen, Wencui
AU - Zhang, Qi
AU - Zhang, Lijuan
AU - Xue, Zhenyi
AU - Li, Yan
AU - Da, Yurong
AU - Yang, Qing
AU - Li, Zesong
AU - Liu, Li
AU - Qiao, Liang
AU - Kong, Ying
AU - Yao, Zhi
AU - Zhao, Peng
AU - Li, Min
AU - Zhang, Rongxin
N1 - Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017/6/15
Y1 - 2017/6/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-16-3146
DO - 10.1158/0008-5472.CAN-16-3146
M3 - Article
C2 - 28446464
AN - SCOPUS:85021115418
SN - 0008-5472
VL - 77
SP - 3194
EP - 3206
JO - Cancer research
JF - Cancer research
IS - 12
ER -