lncRNA CCAT2 promotes radiotherapy resistance for human esophageal carcinoma cells via the miR‑145/p70S6K1 and p53 pathway

Wang,Ming; Wang,Liang; He,Xiang; Zhang,Jinhua; Zhu,Zhongcheng; Zhang,Mingyun; Li,Xingde

doi:10.3892/ijo.2019.4929

lncRNA CCAT2 promotes radiotherapy resistance for human esophageal carcinoma cells via the miR‑145/p70S6K1 and p53 pathway

Authors:
- Ming Wang
- Liang Wang
- Xiang He
- Jinhua Zhang
- Zhongcheng Zhu
- Mingyun Zhang
- Xingde Li
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Affiliations: Department of Radiation Therapy, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China, Department of Digestive Endoscopy, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China, Department of CT Diagnosis, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China, Department of Pediatrics, Mengcun County Hospital, Cangzhou, Hebei 061400, P.R. China
Published online on: December 2, 2019 https://doi.org/10.3892/ijo.2019.4929
Pages: 327-336

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Abstract

The long non‑coding RNA colon cancer‑associated transcript 2 (CCAT2) is abnormally expressed in various types of malignant tumor tissues and considered to be an oncogene, including for esophageal cancer (EC). Radiotherapy is an important and widely used cancer treatment. However, some patients with EC do not respond to radiotherapy. This study was designed to investigate effects of CCAT2 expression on radiotherapy dynamics for EC cells and to explore underlying molecular mechanisms. Reverse transcription‑quantitative PCR was used to measure CCAT2 expression in EC tissues, normal esophageal mucosa, EC cells and normal human esophageal epithelial cells. TUNEL assays were used to assess the effect of CCAT2 on X‑ray‑induced apoptosis of EC cells. Protein expression was detected by western blot. CCAT2 was highly expressed in EC tissues and EC cells, and was negatively associated with radiotherapy efficacy in patients with EC. In vitro, knockdown of CCAT2 enhanced radiosensitivity of EC cells and promoted apoptosis by increasing Bax/Bcl2 and active‑caspase 3/caspase 3 following X‑ray treatment. In addition, CCAT2 negatively regulated miR‑145 and P70 ribosomal protein S6 kinase 1 (p70S6K1) expression, and inhibited phosphorylation of Akt, ERK and p70S6K1 in EC cells. After X‑ray treatment, CCAT2 negatively regulated protein levels of p53, P21 and c‑Myc. These results showed that CCAT2 promoted the radiotherapy resistance of EC cells via negative regulation of the miR‑145/p70S6K1 and the p53 signaling pathways and associated elements may be potential targets for improving the sensitivity of EC radiotherapy.

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