Chen Xiangliu, Huang Yingying, Liu Jin, Lin Wu, Chen Chuanzhi, Chen Yiran, Ding Yongfeng, Yang Yan, Chen Yanyan, Wang Haiyong, Teng Lisong
Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University.
J Cancer. 2022 Feb 28;13(5):1456-1467. doi: 10.7150/jca.69166. eCollection 2022.
Exosome component 5 (EXOSC5) is a non-catalytic component of the RNA exosome complex, which is interacted with the Zinc-finger antiviral protein to degrade the target RNA and aberrantly expressed in various malignances. We explored the molecular mechanisms and biological roles by which EXOSC5 promotes the progression of GC. We used quantitative real-time PCR, Western blotting and immunohistochemistry to analyze EXOSC5 expression in GC samples. An GC organoid-based functional model was assessed, and cancer cell CCK-8 assay, colony formation assay and flow cytometry were performed to reveal the role of EXOSC5 in GC cell proliferation and tumorigenesis. , nude mice tumorigenesis assay were performed to explore the effects of EXOSC5 knockdown on growth of GC. The roles of EXOSC5 on AKT and STAT3 signaling pathways were measured by Western blot. The expression of EXOSC5 was up-regulated in GC tissues and cell lines compared with normal group, and highly expressed EXOSC5 indicated a poorer clinical outcome for GC patients and was positively correlated with tumor size and TNM stage. EXOSC5 overexpression facilitated the growth of GC cells and organoids, while EXOSC5 downregulation inhibited proliferation and induced G1/S phase transition arrest. Moreover, mechanistic studies demonstrated that EXOSC5 increased cyclinD1 expression levels and decreasing the expression levels of p21 and p27 via regulation of the AKT and STAT3 pathway. The expression of EXOSC5 is upregulated and correlated with tumorigenesis and poor prognosis of GC. EXOSC5 increases GC proliferation partly through activating AKT and STAT3 pathways.
外泌体成分5（EXOSC5）是RNA外泌体复合物的一种非催化成分，它与锌指抗病毒蛋白相互作用以降解靶RNA，并在多种恶性肿瘤中异常表达。我们探讨了EXOSC5促进胃癌进展的分子机制和生物学作用。我们使用定量实时PCR、蛋白质免疫印迹和免疫组织化学分析胃癌样本中EXOSC5的表达。评估了基于胃癌类器官的功能模型，并进行癌细胞CCK-8检测、集落形成检测和流式细胞术以揭示EXOSC5在胃癌细胞增殖和肿瘤发生中的作用。进行裸鼠肿瘤发生检测以探究敲低EXOSC5对胃癌生长的影响。通过蛋白质免疫印迹检测EXOSC5对AKT和STAT3信号通路的作用。与正常组相比，EXOSC5在胃癌组织和细胞系中的表达上调，EXOSC5高表达表明胃癌患者的临床预后较差，且与肿瘤大小和TNM分期呈正相关。EXOSC5过表达促进胃癌细胞和类器官的生长，而EXOSC5下调则抑制增殖并诱导G1/S期转变停滞。此外，机制研究表明，EXOSC5通过调节AKT和STAT3通路增加细胞周期蛋白D1的表达水平，并降低p21和p27的表达水平。EXOSC5的表达上调，与胃癌的肿瘤发生和不良预后相关。EXOSC5部分通过激活AKT和STAT3通路增加胃癌增殖。
