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J. Gastroenterol. Hepatol. · Apr 2017
The long noncoding RNA-ROR promotes the resistance of radiotherapy for human colorectal cancer cells by targeting the p53/miR-145 pathway.
- Pengxiang Yang, Yue Yang, Weiwei An, Jianyu Xu, Gan Zhang, Jing Jie, and Qingyuan Zhang.
- Department of Cancer Molecular and Biology, Cancer Research Institute of Harbin Medical University, Harbin, China.
- J. Gastroenterol. Hepatol. 2017 Apr 1; 32 (4): 837-845.
Background And AimLong intergenic noncoding RNAs (lincRNAs) have critical roles in elevating efficacy of anticancer therapy and tumor progression. Recent studies show that Regulator of Reprogramming (ROR) is aberrantly expressed in several types of cancer, including colorectal cancer (CRC). Radiotherapy is considered as a standard preoperative treatment. However, a considerable number of CRCs are resistant to radiotherapy. In this study, we evaluated the role of lincRNA-ROR in radiotherapy for CRC and detected the underlying molecular mechanism.MethodsReal-time polymerase chain reaction was employed to quantify the expression level of lincRNA-ROR in different CRC cell lines and tissue samples. Cell viability and apoptosis assays were used to confirm the radiotherapy-mediated effects by lincRNA-ROR altered expression. The direct impact of lincRNA-ROR on the expression of p53/miR-145 by loss-of-function and gain-of-function strategy was also analyzed. A xenograft mouse model was used to evaluate the role of linc-ROR in CRC treatment.ResultsWe discovered that lincRNA-ROR was upregulated in CRC cell lines and tissue samples. We further showed that knockdown of lincRNA-ROR enhanced the sensitivity to radiotherapy for CRC by inhibiting cell viability and promoting apoptosis. Activity of the p53/miR-145 pathway may help explain the role of lincRNA-ROR for stress-induced regulation in CRC therapy. Combined specific knockdown of lincRNA-ROR and radiotherapy treatment in xenograft model resulted in a significant reduction in the tumor growth.ConclusionLincRNA-ROR decreases sensitivity to radiotherapy via the negative regulation of p53/miR-145 and may represent a potential target for the treatment of CRC.© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
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