miR-181b及其关键靶基因PTEN和TIMP-3在肝细胞肝癌中的表达和意义

MiR-181b and its key target gene PTEN and TIMP-3 expression in hepatocellular carcinoma and significance

目的:研究miR-181b对PTEN和TIMP3基因表达的影响,探讨其在肝细胞肝癌(HCC)发生、发展中的作用及意义。方法:应用免疫组化和实时荧光定量PCR检测30例HCC及相应癌旁组织,10例正常肝脏组织中miR-181b、PTEN、TIMP-3表达情况,分析miR-181b、PTEN和TIMP-3的表达水平与HCC临床病理特征之间的关系。探讨miR-181b水平与PTEN、TIMP3表达的相关性。结果:在HCC组织中PTEN和TIMP-3的m RNA和蛋白的表达水平均明显低于癌旁组织及正常肝组织(P<0.01),调控二者表达的miR-181b在HCC组织中的的表达明显增高。miR-181b、PTEN和TIMP-3的表达水平与HCC细胞的分化程度、血清中AFP表达水平、HBV感染明显有关,与患者年龄、性别、肿瘤大小等因素无关。结论:miR-181b在HCC中的表达量显著高于癌旁和正常肝组织,其表达水平与肿瘤组织细胞的分化程度、血清AFP水平及是否合并HBV感染明显相关;在HCC组织中,miR-181b的表达水平与PTEN、TIMP3的水平呈负相关。miR-181b可能通过靶向调控PTEN和TIMP3的表达来发挥其促进HCC侵袭转移的生物学作用。

Objective： Explore the Effect of miR- 181b in regulating the TIMP3 and PTEN ex- pression, and determine the expression of development and significance of its occurrence in HCC. Methods： Immunohistochemistry （SP method） and SYBR Green real-time fluorescence quantita- tive polymerase chain reaction detected in 30 cases of HCC and corresponding adjacent tissues, 10 normal tissue of PTEN protein and TIMP-3 protein and miR-181b, PTEN, TIMP-3 mRNA expres- sion, analysis of miR-181b. PTEN and TIMP-3 expression in HCC clinical pathologic parameters. And the use of rank correlation miR-181b, respectively, the correlation between PTEN and TIMP3. Results： PTEN and TIMP-3 mRNA and protein expression in the expression levels in HCC were significantly lower than the adjacent normal liver tissue and liver tissue of expression, the difference was statistically significant, P〈O.01, miR-181b in tumor tissues and normal liver tissues was signifi- cantly lower than the expression in HCC. Statistical analysis showed that in HCC miR-181bRNA, PTEN and TIMP-3 gene expression and tumor abnormal tumor differentiation, serum alpha-fetopro- tein expression, a merger of HBV infection and so on, P 〈0.05, with patients age, gender, tumor size and other factors unrelated. Conclusion： miR-181b in hepatocellular carcinoma was significantly higher than in adjacent and normal liver tissue, and miR-181bRNA high expression of the tumor with tumor differentiation, serum alpha-fetoprotein expression, a merger of the HBV infection-related, miR-181b expression of PTEN and TIMP3 negative correlation. Therefore, we hypothesized that miR-181b may exert their biological effects By expression of PTEN and TIMP3 targeted regulation to play a biological role in the promotion of its invasion and metastasis of HCC.