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.
Int J Oncol. 2020 Jan;56(1):327-336. doi: 10.3892/ijo.2019.4929. Epub 2019 Dec 2.
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.
长链非编码 RNA 结肠癌相关转录物 2（CCAT2）在各种类型的恶性肿瘤组织中异常表达，被认为是一种癌基因，包括食管癌（EC）。放射治疗是一种重要且广泛应用的癌症治疗方法。然而，一些 EC 患者对放射治疗没有反应。本研究旨在探讨 CCAT2 表达对 EC 细胞放射动力学的影响及其潜在的分子机制。逆转录定量 PCR 用于测量 EC 组织、正常食管黏膜、EC 细胞和正常人食管上皮细胞中 CCAT2 的表达。TUNEL 测定法用于评估 CCAT2 对 EC 细胞 X 射线诱导凋亡的影响。蛋白质表达通过 Western blot 检测。CCAT2 在 EC 组织和 EC 细胞中高表达，与 EC 患者的放射治疗疗效呈负相关。在体外，CCAT2 敲低增强了 EC 细胞的放射敏感性，并通过增加 Bax/Bcl2 和 X 射线处理后活性 caspase-3/caspase-3 促进细胞凋亡。此外，CCAT2 负调控 miR-145 和 P70 核糖体蛋白 S6 激酶 1（p70S6K1）的表达，并抑制 EC 细胞中 Akt、ERK 和 p70S6K1 的磷酸化。X 射线处理后，CCAT2 负调控 p53、P21 和 c-Myc 的蛋白水平。这些结果表明，CCAT2 通过负调控 miR-145/p70S6K1 和 p53 信号通路及其相关元件促进 EC 细胞的放射抵抗，并且相关元素可能是提高 EC 放射治疗敏感性的潜在靶点。
