长链非编码RNA MAGI2-AS3在喉鳞状细胞癌中的表达及临床意义

Expression of long noncoding RNA MAGI2-AS3 in laryngeal squamous cell carcinoma and their clinical significance

目的探究长链非编码MAGI2反义链RNA3(MAGI2-AS3)在喉鳞状细胞癌中的表达情况及临床意义。方法采用实时荧光定量聚合酶链反应(qRT-PCR)技术检测喉鳞状细胞癌组织及相应癌旁正常黏膜组织中MAGI2-AS3表达情况,分析MAGI2-AS3表达与患者临床特征的关系;同时在喉鳞癌细胞Hep-2中过表达MAGI2-AS3,体外检测细胞的迁移及侵袭能力的变化。结果与癌旁正常黏膜组织相比,喉鳞状细胞癌组织中MAGI2-AS3的相对表达量明显降低,差异有统计学意义(P﹤0.01);声门上型、声门型、声门下型喉鳞状细胞癌患者的MAGI2-AS3表达水平比较,差异无统计学意义(P﹥0.05);低分化喉鳞状细胞癌患者与高、中分化喉鳞状细胞癌患者的MAGI2-AS3表达水平比较,差异无统计学意义(P﹥0.05);T_1+T_2期、无淋巴结转移的喉鳞状细胞癌患者的MAGI2-AS3相对表达量均高于T_3+T_4期、有淋巴结转移的患者,差异均有统计学意义(P﹤0.05)。Hep-2细胞过表达MAGI2-AS3后的迁移、侵袭能力是空载Hep-2细胞的(0.403±0.181)倍和(0.502±0.090)倍,差异均有统计学意义(P﹤0.01)。TCGA公共数据库分析发现MAGI2-AS3在头颈部鳞癌组织中的相对转录水平低于癌旁正常黏膜组织,差异有统计学意义(P﹤0.05);MAGI2-AS3高表达患者的中位生存时间略长于MAGI2-AS3低表达患者,但差异无统计学意义(P﹥0.05)。结论 MAGI2-AS3表达与喉鳞状细胞癌的发生发展相关;体外过表达MAGI2-AS3不仅可明显抑制Hep-2迁移及侵袭能力,还可明显改变上皮细胞-间充质转化(EMT)相关标志物的表达水平,在喉鳞状细胞癌侵袭转移过程中可能发挥重要的生物学作用,有望成为新的分子治疗靶点。

Objective To investigate the expression and clinical significance of long non-coding MAGI2-antisense strand 3 (MAGI2-AS3) in laryngeal squamous cell carcinoma and to discuss their clinical significance. Method The expressions of MAGI2-AS3 in laryngeal squamous cell carcinoma tissues and adjacent normal tissues were determined by real- time quantitative-polymerase chain reaction (qRT-PCR). The relationship between the expressions of MAGI2-AS3 and the clinical characteristics was analyzed;furthermore, the cell migration and invasion abilities laryngeal squamous cell Hep-2 with MAGI2-AS3 overexpression were evaluated. Result The expression of MAGI2-AS3 was significantly decreased in the laryngeal squamous cell carcinoma tissues compared with the normal laryngeal tissues (P<0.01). There were no statistical differences regarding the expression of MAGI2-AS3 among supraglottic, glottic and subglottic laryngeal squamous cell carcinoma (P>0.05). In histological differentiation grouping, no evident differences of MAGI2-AS3 expression were observed between poorly differentiated laryngeal squamous cell carcinoma compared with the well and moderately differentiated laryngeal squamous cell carcinoma (P>0.05). In histological grade grouping, the expression of MAGI2-AS3 in T1+T2 stage diseases was significantly higher than that in T3+T4 stage diseases (P<0.05);moreover, the expression of MAGI2-AS3 in laryngeal squamous cell carcinoma with lymph node metastasis was significantly lower than that without lymph node metastasis (P<0.05). The migration or invasion abilities of the Hep- 2 cells were declined to (0.403±0.181) and (0.502±0.090) times as compared with Hep-2 controls after overexpression of MAGI2-AS3, and the difference was statistically significant (P<0.01). It was found that MAGI2-AS3 was relatively lower in head and neck squamous cell carcinoma than normal adjacent mucosal tissues (P<0.05), and the median survival time of patients with high expression of MAGI2-AS3 was slightly longer than those with low expression, but the difference was not statistically significant (P>0.05), from the analysis of TCGA public database. Conclusion Expression of MAGI2-AS3 may contribute to the carcinogenesis and development of laryngeal squamous cell carcinoma. Overexpression of MAGI2-AS3 in vitro not only significantly inhibits the migration and invasion of Hep-2 cell line, but also alters the expression level of epithelialmesenchymal transition (EMT) related markers, MAGI2-AS3 may be involved in the process of cell invasion and migration, and might be an important therapeutic target in the future.