miR-200家族及侵袭相关基因ZEB1、ZEB2和CTNNB1在颅咽管瘤组织中的表达及意义

Expression and significance of miR-200 family and invasion-related genes ZEB1,ZEB2 and CTNB1 in craniopharyngioma

目的检测miR-200家族及侵袭相关基因ZEB1、ZEB2和CTNNB1在颅咽管瘤组织中的表达并初步探讨其在颅咽管瘤侵袭性生长中的作用。方法收集四川大学华西医院自2017年6月—2018年12月经手术切除的造釉细胞型颅咽管瘤(ACP)30例和鳞状上皮乳头型颅咽管瘤(PCP)30例的新鲜标本,手术切除的失活脑组织作为对照组。HE染色观察病理变化。免疫组化检测E-cadherin和β-catenin的表达。qRT-PCR测定miR-200家族成员及与侵袭相关基因ZEB1、ZEB2和CTNNB1的表达水平。结果HE染色见ACP呈“指样”或“岛样”深入周围脑组织,呈浸润性生长,侵袭性明显。免疫组化示,ACP的β-catenin的表达升高,且分布在细胞质或者细胞核,PCP中β-catenin主要分布在细胞膜上;ACP相对于鳞状细胞型E-cadherin的表达下降。qRT-PCR示,与PCP相比,ACP中miRNA-200家族表达整体下降,组织中mRNA(ZEB1/ZEB2,CTNNB1)表达整体上调。结论miRNA-200家族在颅咽管瘤中可能起到类似于抑癌基因的作用。

Objective To detect the expression of miR-200 family and invasion-related genes ZEB1,ZEB2 and CTNNB1 in craniopharyngioma,and to explore their roles in the invasive growth of craniopharyngioma.Methods Fresh specimens of 30 cases of adamantinomatous craniopharyngiomas(ACP)and 30 cases of papillary craniopharyngiomas(PCP)were collected in West China Hospital of Sichuan University from June 2017 to December 2018.Inactivated brain tissue removed by craniotomy were collected as the control group.The pathological changes were observed by HE staining.The expression of E-cadherin andβ-catenin was detected by immunohistochemistry.The expression levels of miR-200 family members and invasion-related genes ZEB1,ZEB2 and CTNNB1 were determined by qRT-PCR.Results HE staining showed that the ACP was“finger-like”or“island-like”deep into the surrounding brain tissue,showing infiltrating growth and obvious invasiveness.Immunohistochemistry showed that the expression ofβ-catenin in ACP was elevated and distributed in the cytoplasm or nucleus.In PCP,β-catenin was mainly distributed on the cell membrane.Compared with squamous cell type E-cadherin,the expression of ACP decreased.qRT-PCR showed that compared with PCP,the expression of miRNA-200 family in ACP decreased overall.The expression of mRNA(ZEB1/ZEB2,CTNNB1)in the tissues was overall increased.Conclusion The miRNA-200 family may play a role similar to tumor suppressor genes in craniopharyngiomas.