J Cancer 2019; 10(19):4603-4613. doi:10.7150/jca.32065

Research Paper

Long non-coding RNA TUG1 mediates 5-fluorouracil resistance by acting as a ceRNA of miR-197-3p in colorectal cancer

Meng Wang1#, Hanqing Hu1, Yuliuming Wang1, Quanlong Huang1, Rui Huang1, Yinggang Chen1, Tianyi Ma1, Tianyu Qiao1, Qian Zhang1, Hongyu Wu1, Qingmin Chen3, Dong Han2 ✉#, Guiyu Wang1✉, Xishan Wang1,4✉

1. Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China
2. Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150081, China
3. Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang 157011, China
4. Department of Colorectal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100000, China
# These authors contributed equally to the work and should be regarded as joint first authors.

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Citation:
Wang M, Hu H, Wang Y, Huang Q, Huang R, Chen Y, Ma T, Qiao T, Zhang Q, Wu H, Chen Q, Han D, Wang G, Wang X. Long non-coding RNA TUG1 mediates 5-fluorouracil resistance by acting as a ceRNA of miR-197-3p in colorectal cancer. J Cancer 2019; 10(19):4603-4613. doi:10.7150/jca.32065. Available from http://www.jcancer.org/v10p4603.htm

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Abstract

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.

Keywords: Colorectal cancer, TUG1, miR-197-3p, TYMS, ceRNA