Pan Hongda, Pan Jingxin, Song Shibo, Ji Lei, Lv Hong, Yang Zhangru
Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Department of Hematology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Front Oncol. 2019 Jul 18;9:643. doi: 10.3389/fonc.2019.00643. eCollection 2019.
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. 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). experiments including colony formation, Cell Counting Kit-8 (CCK-8), and flow cytometry and 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. 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. 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.
外泌体成分5（EXOSC5）是一种新型的癌症相关基因，在多种恶性肿瘤中异常表达。然而，EXOSC5在结直肠癌（CRC）中的分子机制和生物学作用尚未得到探索。在本研究中，我们研究了EXOSC5促进CRC进展的功能和机制。通过定量实时PCR（qRT-PCR）、蛋白质印迹法和免疫组织化学（IHC）检测了CRC细胞系以及配对的CRC组织和相邻正常组织中EXOSC5的表达。进行了包括集落形成、细胞计数试剂盒-8（CCK-8）、流式细胞术和肿瘤发生试验在内的实验，以探讨EXOSC5对CRC生长的影响。通过蛋白质印迹法检测EXOSC5对ERK和Akt信号通路的影响。与相邻正常组织相比，CRC中EXOSC5的mRNA和蛋白质表达水平上调。IHC分析表明，EXOSC5高表达与预后不良呈正相关。EXOSC5过表达促进了CRC细胞的生长，而EXOSC5敲低导致增殖减少、G1/S期转换停滞。EXOSC5的致癌功能与CRC中ERK和Akt通路的激活有关。EXOSC5在CRC中过表达，并部分通过激活ERK和Akt信号通路促进CRC生长。因此，EXOSC5可能是一种新型癌基因，并可作为CRC的治疗靶点或预后因素。
