Cui Hujun, Zhang Shengqiang, Zhou Hongbo, Guo Ling
Department of Oncology, Affiliated Hongqi Hospital, Mudanjiang Medical University, Mudanjiang, 157011, China.
Department of Thoracic Surgery, Affiliated Hongqi Hospital, Mudanjiang Medical University, Mudanjiang, 157011, China.
Dig Dis Sci. 2017 Aug;62(8):1995-2003. doi: 10.1007/s10620-017-4579-x. Epub 2017 Apr 22.
Esophageal squamous carcinoma (ESC) is one of the most fatal malignancies worldwide with increasing occurrences yet poor outcome. MicroRNAs were reported to play roles in ESC.
We aimed to understand how miRNAs affect the radiotherapy resistance of ESC.
MicroRNA assays, real-time PCR, and Western blot were performed for expression analysis of miR-93 and BTG3. Luciferase activity assay was conducted with mutated B-cell translocation gene 3 (BTG3) 3'-UTR sequence in the 3' end of luciferase sequence with miR-93 inhibitor. ESC cells were treated with irradiation (IR) and clonogenic assay was utilized to detect the cell viability. Human ESC xenograft mouse model was established and subjected to target IR treatment followed by tumor size analysis.
MiR-93 was decreased and BTG3 was increased in ESC cells, with negative correlation of their expression in ESC tissues. MiR-93 directly targeted BTG3 3'-UTR by luciferase activity assay. Either miR-93 inhibition or BTG3 overexpression decreased radiation resistance. Furthermore, miR-93 inhibition suppressed radiation resistance through BTG3.
Direct downregulation of BTG3 by miR-93 is able to render ESC resistant to radiotherapy, and both BTG3 and miR-93 may potentially serve as clinical markers for ESC and contribute to the treatment of ESC.
食管鳞状细胞癌（ESC）是全球最致命的恶性肿瘤之一，其发病率不断上升但预后较差。据报道，微小RNA在食管鳞状细胞癌中发挥作用。
我们旨在了解微小RNA如何影响食管鳞状细胞癌的放疗抵抗性。
进行微小RNA检测、实时定量聚合酶链反应和蛋白质免疫印迹法以分析miR-93和BTG3的表达。用miR-93抑制剂对荧光素酶序列3'端的突变B细胞易位基因3（BTG3）3'-非翻译区序列进行荧光素酶活性检测。用辐射（IR）处理食管鳞状细胞癌细胞，并采用克隆形成试验检测细胞活力。建立人食管鳞状细胞癌异种移植小鼠模型，进行靶向IR治疗，随后分析肿瘤大小。
食管鳞状细胞癌细胞中miR-93表达降低，BTG3表达升高，它们在食管鳞状细胞癌组织中的表达呈负相关。通过荧光素酶活性检测发现miR-93直接靶向BTG3 3'-非翻译区。抑制miR-93或过表达BTG3均可降低放疗抵抗性。此外，抑制miR-93通过BTG3抑制放疗抵抗性。
miR-93直接下调BTG3可使食管鳞状细胞癌对放疗产生抵抗，BTG3和miR-93都可能作为食管鳞状细胞癌的临床标志物，并有助于食管鳞状细胞癌的治疗。
