Yang La, Gu Yuanyuan
Department of Obstetrics and Gynaecology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, P.R. China.
Exp Ther Med. 2023 Apr 24;25(6):277. doi: 10.3892/etm.2023.11977. eCollection 2023 Jun.
Ovarian cancer is as a major contributor to gynaecologic death globally. The present study aimed to investigate the regulatory role of spectrin β non-erythrocytic 2 gene (SPTBN2) in endometroid ovarian cancer and its mechanism of action. According to the Gene Expression Profiling Interactive Analysis (GEPIA) database, SPTBN2 expression is elevated in ovarian cancer tissues and higher SPTBN2 expression indicated a worse prognosis. The present study assessed SPTBN2 mRNA and protein expression levels by reverse transcription-quantitative PCR and western blotting, respectively. Cell viability, proliferation, migration and invasion were assessed with Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine incorporation, wound healing and Transwell assays, respectively. SPTBN2 expression was notably enhanced in ovarian cancer cell lines, especially in A2780 cells compared with HOSEPiC cells (P<0.001). Following transfection with small interfering (si)RNA targeting SPTBN2, the viability, proliferation, migration and invasion of A2780 cells were decreased compared with those of A2780 cells transfected with siRNA-NC (P<0.001). Gene Set Enrichment Analysis database revealed that SPTBN2 was primarily enriched in 'focal adhesion' and 'extracellular matrix (ECM)-receptor interaction', whereas SPTBN2 was significantly associated with integrin β4 (ITGB4) in the GEPIA database. In addition, rescue experiments were performed to determine the mechanism of SPTBN2 in endometroid ovarian cancer. ITGB4 overexpression reversed the inhibitory effects of the SPTBN2 knockdown on viability, proliferation, migration and invasion of A2780 cells (P<0.05). The impacts of SPTBN2 on the expression of focal adhesion and downstream ECM receptor signalling-related proteins, including Src and p-FAK/FAK, were significantly reversed by ITGB4 overexpression (P<0.01). Collectively, SPTBN2 may regulate endometroid ovarian cancer cell proliferation, invasion and migration through the ITGB4-mediated focal adhesion and ECM receptor signalling pathway.
卵巢癌是全球妇科死亡的主要原因。本研究旨在探讨血影蛋白β非红细胞型2基因（SPTBN2）在子宫内膜样卵巢癌中的调控作用及其作用机制。根据基因表达谱交互分析（GEPIA）数据库，SPTBN2在卵巢癌组织中的表达升高，且较高的SPTBN2表达预示着更差的预后。本研究分别通过逆转录定量PCR和蛋白质印迹法评估SPTBN2 mRNA和蛋白质的表达水平。分别使用细胞计数试剂盒-8、5-乙炔基-2'-脱氧尿苷掺入、伤口愈合和Transwell实验评估细胞活力、增殖、迁移和侵袭。与HOSEPiC细胞相比，SPTBN2在卵巢癌细胞系中表达显著增强，尤其是在A2780细胞中（P<0.001）。用靶向SPTBN2的小干扰（si）RNA转染后，与转染siRNA-NC的A2780细胞相比，A2780细胞的活力、增殖、迁移和侵袭能力降低（P<0.001）。基因集富集分析数据库显示，SPTBN2主要富集于“粘着斑”和“细胞外基质（ECM）-受体相互作用”，而在GEPIA数据库中，SPTBN2与整合素β4（ITGB4）显著相关。此外还进行了挽救实验以确定SPTBN2在子宫内膜样卵巢癌中的作用机制。ITGB4过表达逆转了SPTBN2敲低对A2780细胞活力、增殖、迁移和侵袭的抑制作用（P<0.05）。ITGB4过表达显著逆转了SPTBN2对粘着斑和下游ECM受体信号相关蛋白（包括Src和p-FAK/FAK）表达的影响（P<0.01）。总的来说，SPTBN2可能通过ITGB4介导的粘着斑和ECM受体信号通路调节子宫内膜样卵巢癌细胞的增殖、侵袭和迁移。
