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Inhibitory effect of microRNA-129-2 on xenografted human nasopharyngeal carcinoma development and its possible mechanism
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Abstract:
Objective: To investigate the inhibitory effect of microRNA-129-2(miR-129-2) on xenografted human nasopharyngeal carcinoma development and SRY-related HMG-box transcription factor (SOX4) expression in nude mice. Methods: Nude mice were injected with human nasopharyngeal carcinoma CNE1 cells. Animals with confirmed tumor lesions were randomized into 4 treatment groups (n=8): saline control (subcutaneous injection of saline 0.2 ml/d), blank plasmid control (50 μg each mice in 0.2 ml daily), cisplatin (DDP) (1 mg/kg in 0.2 ml daily ) and miR-129-2 (50 μg each mice in 0.2 ml daily). At 5 weeks after treatment, body weight and tumor volume and weight were measured, the proportion of cells at S/G2-M arrest in xenografted tumor cells was assessed by flow cytometry, and SOX4 protein content in xenograft tumors was assessed by immunohistochemical analysis and Western blotting. Results: In nude mice that developed nasopharyngeal carcinoma lesions after grafting of CNE1 cells, miR-129-2 led a significant decrease, comparable to that resulted from DDP treatment, in tumor volume and weight (P<0.01) whereas the control plasmid showed no effect (P>005), as compared with the non-treatment control 22 days after treatment. Mice in the miR-129-2 group were significantly heavier than all other three groups of animals (P<0.01). The proportion of cells at S/G2-M arrest was (37.95±151)% in the non-treatment group, which was not different from the control plasmid group (36.75±1.48)% but significantly decreased (P<0.01) in the miR-129-2 group (31.81±1.45)% and the DDP treatment group (32.34±1.67)%. SOX4 protein content was significantly higher in tumors than in peritumoral tissues (P<0.05). Both miR-129-2 and DDP significantly lowered SOX4 protein content in tumors (P<0.01), but the effect of miR-129-2 was more pronounced. Conclusion: The small non-coding RNA molecule miR-129-2 is capable of suppressing the growth of xenografted human nasopharyngeal carcinoma through down-regulation of SOX4 expression in nude mice, thus possessing a therapeutic potential for nasopharyngeal carcinoma.
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Project Supported:
Project supported by the National Natural Science Foundation of China（No.81373403），the Graduate Research and Innovation Project of Guangxi Province（No.YCSZ2013031），the Research Foundation from the Regional Health Department of Guangxi Province（No.Z202066），and the Youth Foundation of Guangxi Medical University （No.02604001020）
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