Table_3_EXOSC5 as a Novel Prognostic Marker Promotes Proliferation of Colorectal Cancer via Activating the ERK and AKT Pathways.XLSX

Background and Objective: Exosome component 5 (EXOSC5) is a novel cancer-related gene that is aberrantly expressed in various malignances. However, the molecular mechanism and biological role of EXOSC5 have not been explored in colorectal cancer (CRC). In this study, we investigated the functions and mechanisms by which EXOSC5 promotes the progression of CRC.
Methods: EXOSC5 expressions in CRC cell lines and paired CRC and adjacent normal tissues were measured via quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry (IHC). In vitro experiments including colony formation, Cell Counting Kit-8 (CCK-8), and flow cytometry and in vivo tumorigenesis assay were performed to explore the effects of EXOSC5 on growth of CRC. The impacts of EXOSC5 on ERK and Akt signaling pathways were measured by Western blot.
Results: The mRNA and protein expression levels of EXOSC5 were up-regulated in CRC as compared to adjacent normal tissues. IHC analysis indicated that high EXOSC5 level was positively associated with poor prognosis. EXOSC5 overexpression facilitated the growth of CRC cells, while EXOSC5 knockdown led to decreased proliferation, G1/S phase transition arrest. The oncogenic functions of EXOSC5 were associated with activation of the ERK and Akt pathways in CRC.
Conclusion: EXOSC5 is overexpressed in CRC and promotes CRC growth partly through activation of ERK and Akt signaling pathways. Accordingly, EXOSC5 may be a novel oncogene, and acts as a therapeutic target, or prognostic factor for CRC.

背景与目的：外泌体组分5（Exosome component 5, EXOSC5）是一种新型癌相关基因，在多种恶性肿瘤中存在异常表达。然而，目前尚未在结直肠癌（colorectal cancer, CRC）中探究EXOSC5的分子机制与生物学功能。本研究旨在阐明EXOSC5促进结直肠癌进展的功能与作用机制。方法：通过实时荧光定量聚合酶链反应（quantitative real-time PCR, qRT-PCR）、蛋白质印迹法（Western blot）及免疫组织化学染色（immunohistochemistry, IHC），检测结直肠癌细胞系及配对结直肠癌组织与癌旁正常组织中EXOSC5的表达水平。开展体外实验（包括克隆形成实验、细胞计数试剂盒8（Cell Counting Kit-8, CCK-8）检测、流式细胞术）与体内成瘤实验，以探究EXOSC5对结直肠癌生长的影响。通过蛋白质印迹法检测EXOSC5对细胞外调节蛋白激酶（ERK）与蛋白激酶B（Akt）信号通路的调控作用。结果：与癌旁正常组织相比，结直肠癌组织中EXOSC5的mRNA与蛋白表达水平均显著上调。免疫组织化学染色分析显示，EXOSC5高表达与结直肠癌患者不良预后呈正相关。EXOSC5过表达可促进结直肠癌细胞增殖，而EXOSC5敲低则会抑制细胞增殖并诱导G1/S期周期阻滞。EXOSC5的致癌功能与其在结直肠癌中激活ERK与Akt信号通路密切相关。结论：EXOSC5在结直肠癌中呈高表达状态，可通过激活ERK与Akt信号通路部分促进结直肠癌生长。据此，EXOSC5可作为结直肠癌的新型致癌基因、治疗靶点或预后标志物。