Xu Weihua, Hu Junjie, Ma Zhichao, Feng Wanyi, Gong Wei, Fu Shengmiao, Chen Xinping
Department of Medical Laboratory, Hainan Cancer Hospital, Affiliated Cancer Hospital of Hainan Medical University, Hainan Tropical Cancer Research Institute, Haikou, Hainan, 570312, China.
School of Life Sciences, Hainan University, Haikou, Hainan, 570228, China.
Open Med (Wars). 2024 Sep 17;19(1):20241007. doi: 10.1515/med-2024-1007. eCollection 2024.
Metastasis significantly contributes to the poor prognosis of advanced nasopharyngeal carcinoma (NPC). Our prior studies have demonstrated a decrease in BIRC5-206 expression in NPC, which promotes disease progression. However, the role of BIRC5-206 in the invasion and metastasis of NPC has not been fully elucidated. In this study, our objective was to explore the biological function and underlying mechanisms of BIRC5-206 in NPC. Additionally, we established an NPC mouse model of lung invasiveness using C666 cells to assess the impact of BIRC5-206 on NPC metastasis. Our results revealed that silencing BIRC5-206 inhibited apoptosis and enhanced the invasion of NPC cells, whereas its overexpression reversed these effects. Moreover, decreased BIRC5-206 expression significantly increased N-cadherin and Vimentin expression while reducing E-cadherin and occludin levels, both and . Additionally, silencing BIRC5-206 markedly augmented the formation of invasive foci in lung tissues. Rescue experiments further confirmed that decreased BIRC5-206 expression facilitates NPC metastasis via modulation of the miR-145-5p/CD40 signaling pathway. In summary, our study suggests that BIRC5-206 may serve as a potential prognostic biomarker and therapeutic target in the diagnosis and treatment of NPC.
转移是导致晚期鼻咽癌(NPC)预后不良的重要因素。我们之前的研究表明,NPC中BIRC5-206的表达降低,这促进了疾病进展。然而,BIRC5-206在NPC侵袭和转移中的作用尚未完全阐明。在本研究中,我们的目的是探讨BIRC5-206在NPC中的生物学功能及其潜在机制。此外,我们使用C666细胞建立了具有肺侵袭性的NPC小鼠模型,以评估BIRC5-206对NPC转移的影响。我们的结果显示,沉默BIRC5-206可抑制NPC细胞凋亡并增强其侵袭能力,而其过表达则可逆转这些作用。此外,BIRC5-206表达降低显著增加了N-钙黏蛋白和波形蛋白的表达,同时降低了E-钙黏蛋白和闭合蛋白的水平。此外,沉默BIRC5-206显著增加了肺组织中侵袭灶的形成。挽救实验进一步证实,BIRC5-206表达降低通过调节miR-145-5p/CD40信号通路促进NPC转移。总之,我们的研究表明,BIRC5-206可能作为NPC诊断和治疗中的潜在预后生物标志物和治疗靶点。