Liu Tianyu, Chen Jian, Du Qiqiao, Liu Junxiu, Chen Ming, Ooi Shiyin, Huang Jiaming, Wang Wei, Yao Shuzhong
Department of Obstetrics and Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China.
Department of Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China.
Pathol Res Pract. 2021 Jun;222:153450. doi: 10.1016/j.prp.2021.153450. Epub 2021 Apr 15.
Family with sequence similarity 83 member A (FAM83A) is a member of the FAM83 family and is proven to have oncogenic properties in several cancers. However, the mechanisms of FAM83A in human cervical cancer (CC) progression are unknown. Here, we found that FAM83A is highly expressed in CC tissues and cell lines through western blot and qRT-PCR. We utilized GEO datasets to assess FAM83A expression in CC in comparison to the normal cervical tissue (NCT) (GSE6791), and similarly, in lymph node positive CC compared to the lymph node negative CC (GSE26511). Immunohistochemistry (IHC) was used to quantify FAM83A expression in 20 NCT and 105 CC patient samples. FAM83A expression is upregulated in early-stage CC and correlates with aggressive clinicopathologic features. Moreover, both our hospital's and TCGA datasets revealed that patients of early-stage CC with higher FAM83A expression had a poorer prognosis. Subsequently, CCK-8 and transwell assays verified that FAM83A promotes proliferation, migration, and invasion of CC cells. Additionally, Gene Set Enrichment Analysis (GSEA) revealed that FAM83A is not only involved in cell development, differentiation, and proliferation but is also correlated with cell junction assembly and cell matrix adhesion. It might also be affiliated with the regulation of tumor necrosis factor-mediated signaling pathway and the regulation of the ErbB signaling pathway in CC. These results indicate that FAM83A promotes tumor cell proliferation, migration, and metastasis. Our study provides novel evidence FAM83A may act as a promising therapeutic target for CC.
序列相似性家族83成员A（FAM83A）是FAM83家族的一员，已被证实在多种癌症中具有致癌特性。然而，FAM83A在人类宫颈癌（CC）进展中的机制尚不清楚。在这里，我们通过蛋白质免疫印迹和定量逆转录聚合酶链反应发现FAM83A在CC组织和细胞系中高表达。我们利用基因表达综合数据库（GEO）数据集评估与正常宫颈组织（NCT）相比CC中FAM83A的表达（GSE6791），同样地，评估淋巴结阳性CC与淋巴结阴性CC相比FAM83A的表达（GSE26511）。免疫组织化学（IHC）用于量化20份NCT和105份CC患者样本中FAM83A的表达。FAM83A表达在早期CC中上调，并与侵袭性临床病理特征相关。此外，我们医院和癌症基因组图谱（TCGA）数据集均显示，FAM83A表达较高的早期CC患者预后较差。随后，细胞计数试剂盒-8（CCK-8）和Transwell实验证实FAM83A促进CC细胞的增殖、迁移和侵袭。此外，基因集富集分析（GSEA）显示FAM83A不仅参与细胞发育、分化和增殖，还与细胞连接组装和细胞基质黏附相关。它可能还与CC中肿瘤坏死因子介导的信号通路调控以及表皮生长因子受体（ErbB）信号通路调控有关。这些结果表明FAM83A促进肿瘤细胞增殖、迁移和转移。我们的研究提供了新的证据，表明FAM83A可能是CC一个有前景的治疗靶点。
