Liu Yao, Zhang Bing, Shi Tiefeng, Qin Huadong
The Fourth Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
Onco Targets Ther. 2017 Feb 24;10:1115-1122. doi: 10.2147/OTT.S110468. eCollection 2017.
Chemotherapy is one of the most effective forms of cancer treatment and has been used in the treatment of various malignant tumors. We have gained significant insight into the mechanisms of chemoresistance but the details of the molecular mechanisms remain unclear. In the present study, we found that tripartite motif 8 (TRIM8) expression was downregulated in anaplastic thyroid cancer (ATC) tissues and cell lines. This downregulation of TRIM8 was significantly correlated with the upregulation of miR-182 in human ATC tissues. Bioinformatic analysis and luciferase reporter assays identified TRIM8 as a direct target of miR-182 in ATC. A functional assay using an MTT assay and colony formation showed that miR-182 induced cellular growth by repressing TRIM8 expression. Additionally, overexpressed miR-182 contributed to the chemoresistance of ATC cells by the repression of TRIM8 expression. In conclusion, these results demonstrate that miR-182/TRIM8 may be a therapeutic target for the treatment of chemoresistant human thyroid papillary cancer.
化疗是最有效的癌症治疗方式之一,已被用于各种恶性肿瘤的治疗。我们对化疗耐药机制有了重要认识,但分子机制的细节仍不清楚。在本研究中,我们发现三方基序8(TRIM8)在间变性甲状腺癌(ATC)组织和细胞系中的表达下调。TRIM8的这种下调与人类ATC组织中miR-182的上调显著相关。生物信息学分析和荧光素酶报告基因检测确定TRIM8是ATC中miR-182的直接靶点。使用MTT法和集落形成的功能分析表明,miR-182通过抑制TRIM8表达诱导细胞生长。此外,过表达的miR-182通过抑制TRIM8表达促进了ATC细胞的化疗耐药性。总之,这些结果表明miR-182/TRIM8可能是治疗化疗耐药性人类甲状腺乳头状癌的治疗靶点。