Journal
JOURNAL OF CANCER
Volume 10, Issue 19, Pages 4603-4613Publisher
IVYSPRING INT PUBL
DOI: 10.7150/jca.32065
Keywords
Colorectal cancer; TUG1; miR-197-3p; TYMS; ceRNA
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Funding
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2016I2M-1-001]
- Beijing Science and Technology Program [D17110002617004]
- University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province [UNPYSCT-2017072]
- Heilongjiang Health and Family Planning Commission Research project [2017-064]
- Fundamental Research Funds for the Provincial Universities
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One major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to fluoropyrimidine (Fu)-based chemotherapy. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in cancerous processes as either oncogenes or tumor suppressor genes. Here, we observed lncRNA TUG1 was associated to the 5-Fu resistance in colorectal cancer. Firstly, quantitative analysis indicated that TUG1 was significantly increased in recurrence CRC patient samples. Kaplan-Meier survival analysis indicated that high TUG1 expression in CRC tissues was significantly associated with a higher rate of disease progression. TUG1 knockdown re-sensitized the 5-Fu resistance in colorectal cancer cells, which were 5-Fu-resistant colorectal cell line. Furthermore, bioinformatics analysis showed that miR-197-3p could directly bind to TUG1 suggesting TUG1 might work as a ceRNA to sponge miR-197-3p. Extensively, our study also showed that TYMS was the direct target of miR-197-3p in CRC cells. Taken together, our study suggests that TUG1 mediates 5-Fu resistance in CRC via miR-197-3p/TYMS axis.
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