Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer (CRC) patients. The role of the differentially expressed lncRNAs in 5-Fluorouracil chemoresistance has not fully explained. Here, we observed lncRNA H19 was associated with the 5-Fu resistance in CRC. Quantitative analysis indicated that H19 was significantly increased in recurrent CRC patient samples. Kaplan–Meier survival analysis indicated that high H19 expression in CRC tissues was significantly associated with poor recurrent free survival. Our functional studies demonstrated that H19 promoted colorectal cells 5-Fu resistance. Mechanistically, H19 triggered autophagy via SIRT1 to induce cancer chemoresistance. Furthermore, bioinformatics analysis showed that miR-194–5p could directly bind to H19, suggesting H19 might work as a ceRNA to sponge miR-194–5p, which was confirmed by Dual-luciferase reporter assay and Immunoprecipitation assay. Extensively, our study also showed that SIRT1 is the novel direct target of miR-194–5p in CRC cells. Taken together, our study suggests that H19 mediates 5-Fu resistance in CRC via SIRT1 mediated autophagy. Our finding provides a novel mechanistic role of H19 in CRC chemoresistance, suggesting that H19 may function as a marker for prediction of chemotherapeutic response to 5-Fu.

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MicroRNAs (miRNAs) are deregulated in a number of cancers including colorectal cancer. MiR-30c belongs to miR-30 family, and is involved in a variety of malignant diseases. In this study, we detected the expression of miR-30c in colon cancer cell lines and clinical colon cancer specimens. MiR-30c was shown to be dramatically down-regulated both in cell lines and cancer tissues. Additionally, miR-30c could inhibit cancer cell growth, migration and invasion in vitro. Consistently, stable over-expression of miR-30c inhibited the growth and lung metastasis of colon cancer cell xenografts in vivo. Furthermore, bioinformatics algorithm and luciferase reporter assay indicated ADAM19 as a direct target of miR-30c. Of interest, further experiments demonstrated that inhibition of ADAM19 by miR-30c partially mediated the anti-tumor effect of miR-30c. Overall, our study provides the new insight that miR-30c inhibited colon cancer cells via targeting ADAM19. Thus, miR-30c might serve as a promising therapeutic strategy for colon cancer treatment.

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.