lncRNA CCAT2 promotes radiotherapy resistance for human esophageal carcinoma cells via the miR‑145/p70S6K1 and p53 pathway
| Autor: | Zhongcheng Zhu, Xiang He, Xingde Li, Liang Wang, Mingyun Zhang, Jinhua Zhang, Ming Wang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Cancer Research Esophageal Neoplasms Cell Caspase 3 P70-S6 Kinase 1 Apoptosis Biology Radiation Tolerance 03 medical and health sciences 0302 clinical medicine medicine Biomarkers Tumor Tumor Cells Cultured Humans Radiosensitivity Protein kinase B Cell Proliferation Oncogene Ribosomal Protein S6 Kinases 70-kDa Cell cycle Middle Aged Prognosis Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic Survival Rate MicroRNAs 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Ribosomal protein s6 Cancer research Female RNA Long Noncoding Esophageal Squamous Cell Carcinoma Tumor Suppressor Protein p53 Follow-Up Studies |
| Zdroj: | International journal of oncology. 56(1) |
| ISSN: | 1791-2423 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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