Department of Otolaryngology and Stomatology, Shouguang People's Hospital, Shouguang, Shandong 262700, P.R. China.
Department of Otolaryngology and Maxillofacial Surgery, Wuwei People's Hospital, Wuwei, Gansu 733000, P.R. China.
Mol Med Rep. 2021 Sep;24(3). doi: 10.3892/mmr.2021.12290. Epub 2021 Jul 19.
Forkhead‑box gene 1 (FOXG1) has been reported to serve an important role in various malignancies, but its effects on nasopharyngeal cancer (NPC) remain unknown. Thus, the present study aimed to investigate the specific regulatory relationship between FOXG1 and NPC progression. Tumor tissues and matching para‑carcinoma tissues were obtained from patients with NPC. Small interfering (si)RNA‑FOXG1 and pcDNA3.1‑FOXG1 were transfected into SUNE‑1 and C666‑1 cells to knockdown and overexpress FOXG1 expression, respectively. FOXG1 expression was detected using reverse transcription‑quantitative PCR and immunohistochemistry. Cell proliferation was detected using MTT and 5‑ethynyl‑20‑deoxyuridine assays. Transwell invasion assay, wound healing assay and flow cytometry were used to detect cell invasion, migration and apoptosis, respectively. Western blotting was conducted to detect the expression levels of mitochondrial markers (succinate dehydrogenase complex flavoprotein subunit A, heat shock protein 60 and pyruvate dehydrogenase), epithelial‑mesenchymal transition (EMT) related proteins (N‑cadherin, Snail and E‑cadherin) and apoptosis‑related proteins [Bax, Bcl‑2, poly(ADP‑ribose) polymerase 1 (PARP), cleaved PARP, cleaved caspase‑3, cleaved caspase‑8, cleaved caspase‑9, caspase‑3, caspase‑8 and caspase‑9]. The mitochondrial membrane potential was detected via flow cytometry, while the ATP/ADP ratio was determined using the ADP/ATP ratio assay kit. The present results demonstrated that FOXG1 expression was upregulated in NPC tissues and cells, and was associated with distant metastasis and TNM stage. Moreover, knockdown of FOXG1 inhibited the proliferation, migration, invasion, EMT and mitochondrial function of SUNE‑1 cells, as well as promoted cell apoptosis, while the opposite results were observed in C666‑1 cells. In conclusion, FOXG1 enhanced proliferation, migration and invasion, induced EMT and improved mitochondrial function in NPC cells. The current findings provide an adequate theoretical basis for the treatment of NPC.
叉头框基因 1（FOXG1）已被报道在多种恶性肿瘤中发挥重要作用，但它在鼻咽癌（NPC）中的作用尚不清楚。因此，本研究旨在探讨 FOXG1 与 NPC 进展之间的特定调控关系。从 NPC 患者中获得肿瘤组织和匹配的癌旁组织。将小干扰 RNA（siRNA）-FOXG1 和 pcDNA3.1-FOXG1 转染到 SUNE-1 和 C666-1 细胞中，分别下调和过表达 FOXG1 表达。采用逆转录-定量 PCR 和免疫组织化学检测 FOXG1 表达。采用 MTT 和 5-乙炔基-20-脱氧尿苷检测细胞增殖。采用 Transwell 侵袭实验、划痕愈合实验和流式细胞术分别检测细胞侵袭、迁移和凋亡。采用 Western blot 检测线粒体标志物（琥珀酸脱氢酶复合物黄素蛋白亚单位 A、热休克蛋白 60 和丙酮酸脱氢酶）、上皮-间质转化（EMT）相关蛋白（N-钙粘蛋白、Snail 和 E-钙粘蛋白）和凋亡相关蛋白[Bax、Bcl-2、多聚（ADP-核糖）聚合酶 1（PARP）、裂解 PARP、裂解 caspase-3、裂解 caspase-8、裂解 caspase-9、caspase-3、caspase-8 和 caspase-9]的表达水平。采用流式细胞术检测线粒体膜电位，采用 ADP/ATP 比测定试剂盒检测 ATP/ADP 比值。结果表明，FOXG1 在 NPC 组织和细胞中表达上调，与远处转移和 TNM 分期有关。此外，下调 FOXG1 抑制了 SUNE-1 细胞的增殖、迁移、侵袭、EMT 和线粒体功能，并促进了细胞凋亡，而在 C666-1 细胞中则观察到相反的结果。综上所述，FOXG1 增强了 NPC 细胞的增殖、迁移和侵袭能力，诱导 EMT 并改善了线粒体功能。本研究结果为 NPC 的治疗提供了充分的理论依据。
