口腔鳞癌中let-7a、miR-21和miR-27a的表达及其作用

Expression and effect of let-7a,miR-21 and miR-27a in oral squamous cell carcinomas

目的探讨let-7a、miR-21和miR-27a在口腔鳞状细胞癌(OSCCs)中的表达及其作用。方法采用地高辛标记的锁定核酸修饰的miRNA探针进行原位杂交,对5例正常口腔黏膜组织和30例口腔鳞癌及其癌旁组织中let-7a、miR-21、miR-27a的表达进行定性、定位研究,通过图像分析对实验结果进行了半定量分析。结果let-7a、miR-21和miR-27a分别在40%(2/5)、80%(4/5)、40%(2/5)的正常口腔黏膜组织中有微弱表达,而在肿瘤组织和癌旁组织均有不同程度的表达。这3种miRNAs在口腔鳞癌组织中的表达均明显高于其癌旁组织和正常组织(P<0.01),let-7a和miR-27a在癌旁组织中的表达明显高于正常组织(P<0.01),但miR-21在癌旁组织和正常组织中的表达差异无显著性(P>0.05)。这3种miRNAs的表达在不同年龄、不同性别及有无淋巴结转移的口腔鳞癌患者之间的差异均无显著性(P>0.05)。miR-27a在中低分化口腔鳞癌组织中的表达明显高于其在高分化肿瘤组织中的表达(P<0.05),而let-7a和miR-21的表达与肿瘤分化程度无关(P>0.05)。相关分析发现,OSCCs中let-7a与miR-21的表达之间具有相关性,而miR-27a与let-7a和miR-21表达之间均无相关性。结论 Let-7a、miR-21和miR-27a过度表达在口腔鳞癌发生发展中具有一定作用,miR-27a可能是与口腔鳞癌分化程度有关的一个分子标志。在OSCCs中let-7a和miR-21之间可能存在一定联系。

Objective To explore the expression and function of let-7a,miR-21 and miR-27 a in oral squamous cell carcinomas（ OSCCs）. Methods Using in situ hybridization by dig-marked miRCURY LNATMmicroRNA detection probes,the expressions levels of let-7a,miR-21 and miR-27 a were studied on nature and localization in 5 normal oral mucous tissues,30 OSCCs and their paired pericarcinomatous tissues. The results of microRNAs expression were semiquantitatively analyzed by image analysis. Results The expressions of let-7a,miR-21 and miR-27 a were weak,and only found in 40%（ 2 /5）,80%（ 4 /5） and 40%（ 2 /5） normal oral mucous tissues,respectively. But all the tumor tissues and their pericarcinomatous tissues expressed the three miRNAs in different extent. The expression levels of three miRNAs in OSCCs were much higher than that in pericarcinomatous tissues and normal tissues（ P〈0. 01）. The expression of let-7a and miR-27 a in pericarcinomatous tissues was obviously higher than that in normal tissues（ P〈0. 01）,however,no obvious difference was observed between the expression of miR-21 in pericarcinomatous tissues and in normal tissues（ P〉0. 05）. No significant difference was detected in OSCC patients with different age and sex,and lymphatic metastasis or not（ P〉0. 05）. The expression of miR-27 a in moderate/low differentiated OSCCs was higher than its expression in high differentiated OSCCs（ P〈0. 05）. No statistical difference of miR-21 and let-7a expression was found in differentiation-different OSCCs（ P〉0. 05）. Correlation analysis showed that there was positive correlation between expression of let-7a and miR-21 in OSCCs,but no correlation was found between expression of miR-27 a and let-7a / miR-21. Conclusion The overexpression patterns of let-7a,miR-21 and miR-27 a play a certain role in tumorgenesis and development of OSCCs.miR-27 a is an expected molecular marker associated with differentiated degree of OSCCs. There is a certain relation between let-7a and miR-21 in OSCCs.