Expression and significance of tumor suppressor SUFU in ovarian cancer
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摘要:
目的：探讨卵巢癌中抑癌因子SUFU（suppressor of Fused）表达变化及其意义。方法：通过免疫组化检测人卵巢癌和癌旁组织样本中SUFU的表达量，并在数据库大样本和细胞水平上进行验证。同时在人正常卵巢上皮细胞系IOSE80和卵巢癌细胞系SKOV3分别抑制和过表达SUFU后，运用MTT、EdU、流式细胞术、Western blot、Transwell、平板克隆形成实验等方法分别检测细胞的增殖、凋亡、上皮间充质转化（epithelial-mesenchymal transition，EMT）、迁移与侵袭的情况，并随后用Western blot和实时定量PCR（quantitative real-time PCR，qPCR）检测Sonic Hedgehog（SHH）信号通路的下游靶基因GLI1蛋白和mRNA水平。结果：在3例卵巢癌组织样本中，相比于癌旁组织，癌组织中SUFU蛋白表达有一定下调，而这个结果在TCGA数据库大样本中也得到验证；此外在细胞水平上，人正常卵巢上皮细胞IOSE80中SUFU蛋白和mRNA表达水平明显高于卵巢癌细胞SKOV3。进一步在SKOV3细胞中过表达SUFU能够有效抑制其增殖、EMT、克隆形成、迁移和侵袭，促进凋亡；相反，在IOSE80细胞中下调SUFU则能够促进细胞EMT、迁移和侵袭能力。同时，相比正常卵巢上皮细胞，卵巢癌细胞中GLI1 mRNA和蛋白水平明显上升；当在卵巢癌细胞中上调SUFU时，SHH信号通路的下游靶基因GLI1的表达则明显下调。结论：SUFU能够抑制卵巢癌的发生发展，其作用机制与SHH信号通路相关。
Abstract:
Objective：This study aims to investigate the expression and significance of tumor suppressor SUFU（Suppressor of Fused）in ovarian cancer. Methods：We detected the expression of SUFU in human ovarian cancer and adjacent tissues by immunohistochemistry，and verified the results in large samples and at the cellular level. Then MTT，EdU，flow cytometry，Western blot，Transwell，cloning formation experiments were used to detect cell proliferation，apoptosis，epithelial-mesenchymal transition（EMT），migration and invasion after regulating the expression of SUFU in the human normal ovarian epithelial cell line IOSE80 and the ovarian cancer cell line SKOV3 respectively. Meanwhile，the protein and mRNA levels of target gene GLI1 in the Sonic Hedgehog（SHH）signaling pathway were detected by Western blot and quantitative real-time PCR（qPCR）. Results：In three ovarian cancer tissue samples，SUFU in cancer tissues was downregulated compared to adjacent tissues，and this result was also confirmed in large samples of the TCGA database. In addition，at the cellular level，SUFU was higher in the human normal ovarian epithelial cell line IOSE80 than in the ovarian cancer cell line SKOV3. Further overexpression of SUFU in SKOV3 cells can effectively inhibit proliferation，EMT，colony formation，migration and invasion，and promote apoptosis；on the contrary，downregulation of SUFU in IOSE80 cells can promote cell EMT，migration and invasion. At the same time，GLI1 mRNA and protein levels were significantly
