Hu Xiang, Han Tong, Bian Yiding, Tong Huan, Wen Xiaoli, Li Yiran, Wan Xiaoping
Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, P.R. China.
Oncol Rep. 2020 Mar;43(3):919-929. doi: 10.3892/or.2020.7478. Epub 2020 Jan 23.
Endometrial cancer (EC) is the second leading type of cancer among women, and its progression is dependent on several factors. The aim of the present study was to examine the effect of solute carrier organic anion transporter family member 4C1 (SLCO4C1) on human EC and determine the underlying molecular mechanism. A total of 57 differentially expressed genes associated with advanced stage and survival were identified in The Cancer Genome Atlas database. In addition, gene ontology analysis indicated that SLCO4C1 was highly expressed in cell differentiation and integral component of plasma membrane. High SLCO4C1 expression in EC tissues was verified by immunohistochemistry. The results demonstrated that the downregulation of SLCO4C1 could significantly suppress the viability, sphere formation, migration and invasion abilities of cells, but enhance apoptosis in EC cell lines. Furthermore, the present results demonstrated that SLCO4C1 had effects on the epithelial‑mesenchymal transition (EMT) phenotype in EC cells and regulated the expression of EMT‑related proteins. Mechanistically, the present study revealed that SLCO4C1 regulated the biological functions of EC cells by inactivating the PI3K/Akt signaling pathway. Collectively, it was demonstrated that the SLCO4C1/PI3K/Akt pathway may play an important role in EC progression and metastasis and serve as a potential biomarker and target for EC diagnosis and treatment.
子宫内膜癌（EC）是女性中第二大常见癌症类型，其进展取决于多种因素。本研究的目的是检测溶质载体有机阴离子转运蛋白家族成员4C1（SLCO4C1）对人子宫内膜癌的影响，并确定其潜在的分子机制。在癌症基因组图谱数据库中总共鉴定出57个与晚期和生存相关的差异表达基因。此外，基因本体分析表明，SLCO4C1在细胞分化和质膜整合成分中高表达。通过免疫组织化学验证了子宫内膜癌组织中SLCO4C1的高表达。结果表明，SLCO4C1的下调可显著抑制细胞的活力、成球能力、迁移和侵袭能力，但可增强子宫内膜癌细胞系的凋亡。此外，本研究结果表明，SLCO4C1对子宫内膜癌细胞的上皮-间质转化（EMT）表型有影响，并调节EMT相关蛋白的表达。机制上，本研究表明，SLCO4C1通过使PI3K/Akt信号通路失活来调节子宫内膜癌细胞的生物学功能。总的来说，证明了SLCO4C1/PI3K/Akt通路可能在子宫内膜癌的进展和转移中起重要作用，并作为子宫内膜癌诊断和治疗的潜在生物标志物和靶点。
