Huang Runqing, Li Jianxia, Fu Yang, Deng Yanhong
Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Guangdong Research Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Ann Transl Med. 2021 Sep;9(17):1391. doi: 10.21037/atm-21-4244.
Feminization-1 (FEM-1) is considered a substrate recognition subunit of CUL2-RING E3 ubiquitin ligase complexes, which refers to sex determination by modulating TRA-1 stability in . The function of mammalian orthologous gene of FEM-1 remains to be elucidated.
The expression of FEM1C in colorectal cancer (CRC) cells was interfered by small interference RNA (siRNA) transfection, and Cell counting kit-8 (CCK-8) assay, colony formation assay and transwell assay were performed. In order to estimate the function on metastasis, stable knockdown FEM1C cells were used to established liver and lung metastasis models. In addition, the expression of FEM1C in normal tissues, adenomas and tumor tissues were analyzed, and the relationship between FEM1C expression level and prognosis was analyzed by Kaplan-Meier method.
Here, we report that the elimination of FEM1C, one of the members of FEM-1, significantly promoted the migration and invasion of colorectal cancer (CRC) cells and promoted liver and lung metastases . It also showed that the removal of FEM1C improved the proliferation ability of CRC cells. In particular, the cell shape changed from epithelial to fibroblast-like morphology. The tight cell monolayer was transformed into a dispersed distribution. Furthermore, it was demonstrated that FEM1C is down-regulated in tissues of CRC compared to normal tissues, and the high expression of FEM1C positively correlates with a good prognosis in patients with CRC. GSEA analysis showed that EMT signatures was enriched in FEM1C knockdown groups.
Down-regulation of FEM1C promotes proliferation and metastasis, and FEM1C may be a tumor suppressor in the development of CRC.
Feminization-1（FEM-1）被认为是CUL2-RING E3泛素连接酶复合物的底物识别亚基，其通过调节TRA-1的稳定性参与性别决定。FEM-1哺乳动物直系同源基因的功能仍有待阐明。
通过小干扰RNA（siRNA）转染干扰结直肠癌（CRC）细胞中FEM1C的表达，并进行细胞计数试剂盒-8（CCK-8）检测、集落形成检测和Transwell检测。为评估其对转移的作用，使用稳定敲低FEM1C的细胞建立肝转移和肺转移模型。此外，分析了FEM1C在正常组织、腺瘤和肿瘤组织中的表达，并采用Kaplan-Meier法分析FEM1C表达水平与预后的关系。
在此，我们报道FEM-1成员之一FEM1C的缺失显著促进了结直肠癌（CRC）细胞的迁移和侵袭，并促进了肝转移和肺转移。还表明去除FEM1C提高了CRC细胞的增殖能力。特别是，细胞形态从上皮样变为成纤维细胞样形态。紧密的细胞单层转变为分散分布。此外，证明与正常组织相比，FEM1C在CRC组织中表达下调。FEM1C的高表达与CRC患者的良好预后呈正相关。基因集富集分析（GSEA）表明EMT特征在FEM1C敲低组中富集。
FEM1C的下调促进增殖和转移，FEM1C可能是CRC发生发展中的一种肿瘤抑制因子。
