Hao Yanru, Li Junan, Zhang Hejia, Guan Guofang, Guo Yingyuan
Department of Otolaryngology Head and Neck Surgery, the Second Hospital of Jilin University, Changchun, Ji Lin, China, 130000.
J BUON. 2020 Jan-Feb;25(1):350-356.
Nasopharyngeal carcinoma is one of the lethal cancers prevalent in Southeast Asia and Southern China. The frequent relapses, development of drug resistance, the adverse effects of chemotherapy and lack of therapeutic targets form the major hurdles in nasopharyngeal carcinoma treatment. This study was undertaken to investigate the role and therapeutic potential of miR-205 in human nasopharyngeal carcinoma cells.
Expression analysis was performed by qRT-PCR. The WST-1 and colony formation assays were used for the assessment of the cell viability. Autophagy was detected by electron microscopy and apoptosis was detected by DAPI staining. Protein expression was determined by western blot analysis.
The expression of miR-205 was significantly downregulated in human nasopharyngeal carcinoma cells. Overexpression of miR-205 caused significant inhibition in the proliferation of CNE1 nasopharyngeal carcinoma cells. The miR-205-triggered growth inhibition was found to be mainly due to the induction of autophagy which was associated with increase in LC3B II and decrease in p62 expression. The miR-205 overexpression also caused apoptotic cell death of CNE1 cells which was concomitant with increase in the Bax/Bcl-2 ratio. Additionally, miR-205 enhanced the chemosensitivity of the nasopharyngeal carcinoma cells to cisplatin and suppressed their migration and invasiveness. In silico analysis showed that miR-205 exerts its effects by inhibiting human epidermal growth factor receptor 3 (HER3). The expression of HER3 was found to be significantly upregulated in nasopharyngeal carcinoma cells and overexpression of HER3 could nullify the effects of miR-205 on the proliferation of nasopharyngeal carcinoma cells.
miR-205 may exhibit therapeutic implications in the treatment of nasopharyngeal carcinoma.
鼻咽癌是东南亚和中国南方常见的致命癌症之一。频繁复发、耐药性的产生、化疗的副作用以及缺乏治疗靶点构成了鼻咽癌治疗的主要障碍。本研究旨在探讨miR-205在人鼻咽癌细胞中的作用及治疗潜力。
通过qRT-PCR进行表达分析。采用WST-1和集落形成试验评估细胞活力。通过电子显微镜检测自噬，通过DAPI染色检测凋亡。通过蛋白质印迹分析确定蛋白质表达。
miR-205在人鼻咽癌细胞中的表达显著下调。miR-205的过表达导致CNE1鼻咽癌细胞的增殖受到显著抑制。发现miR-205引发的生长抑制主要是由于自噬的诱导，这与LC3B II的增加和p62表达的降低有关。miR-205的过表达还导致CNE1细胞凋亡性死亡，这与Bax/Bcl-2比值的增加相伴。此外，miR-205增强了鼻咽癌细胞对顺铂的化疗敏感性，并抑制了它们的迁移和侵袭性。计算机分析表明，miR-205通过抑制人表皮生长因子受体3（HER3）发挥其作用。发现HER3在鼻咽癌细胞中的表达显著上调，HER3的过表达可消除miR-205对鼻咽癌细胞增殖的影响。
miR-205在鼻咽癌治疗中可能具有治疗意义。
