UBE2C 通过 AKT/mTOR 信号通路影响乳腺癌的增殖。
UBE2C affects breast cancer proliferation through the AKT/mTOR signaling pathway.
机构信息
Department of Mammary/Head and Neck Surgery, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, China.
Department of Institute for Cancer Research, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, China.
出版信息
Chin Med J (Engl). 2021 Oct 7;134(20):2465-2474. doi: 10.1097/CM9.0000000000001708.
BACKGROUND
Ubiquitin-conjugating enzyme E2C (UBE2C) has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes. This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer (BC) proliferation.
METHODS
BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Then differentially expressed genes (DEGs) were identified using Venn diagram analysis. By using DEGs, we conducted the following analyses including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and survival analysis, and then validated the function of the hub gene UBE2C using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, transwell assay, and Western blot assay.
RESULTS
In total, 151 DEGs were identified from the GEO and TCGA databases. The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division, lipid droplet, and organic acid-binding. KEGG analysis showed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category. The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. The results of survival analysis showed a close relationship between UBE2C and BC. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P < 0.050). The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10 (p-PTEN) was obviously increased (P < 0.050), whereas the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and hypoxia-inducible factor-1 alpha (HIF-1α) were dramatically decreased (P < 0.050) in the UBE2C knockdown cell.
CONCLUSION
UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.
背景
泛素结合酶 E2C（UBE2C）已被证明与各种癌症的发生有关，并参与许多肿瘤发生过程。本研究旨在探讨 UBE2C 影响乳腺癌（BC）增殖的具体分子机制。
方法
根据基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库中的筛选标准筛选与 BC 相关的数据集。然后使用 Venn 图分析鉴定差异表达基因（DEGs）。利用 DEGs，我们进行了基因本体论（GO）、京都基因与基因组百科全书（KEGG）、蛋白质-蛋白质相互作用（PPI）和生存分析等分析，然后使用定量逆转录-聚合酶链反应（RT-qPCR）、细胞计数试剂盒-8（CCK-8）测定、Transwell 测定和 Western blot 测定验证了枢纽基因 UBE2C 的功能。
结果
从 GEO 和 TCGA 数据库中总共鉴定出 151 个 DEGs。GO 分析的结果表明，DEGs 显著富集于有丝分裂核分裂、脂滴和有机酸结合。KEGG 分析显示，过氧化物酶体增殖物激活受体（PPAR）信号通路、脂肪细胞脂解调节和近端肾小管碳酸氢盐回收在信号转导途径类别中显著富集。PPI 网络中排名前三的枢纽基因是 FOXM1、UBE2C 和 CDKN3。生存分析的结果表明，UBE2C 与 BC 密切相关。CCK-8 和 Transwell 测定的结果表明，UBE2C 敲低细胞的增殖和侵袭能力明显受到抑制（P<0.050）。Western blot 测定的结果表明，磷酸化磷酸酶和张力蛋白同源物缺失的染色体 10（p-PTEN）的水平明显升高（P<0.050），而磷酸化蛋白激酶 B（p-AKT）、磷酸化哺乳动物雷帕霉素靶蛋白（p-mTOR）和缺氧诱导因子-1α（HIF-1α）的水平显著降低（P<0.050）在 UBE2C 敲低细胞中。
结论
UBE2C 通过激活 AKT/mTOR 信号通路促进 BC 的增殖。
Zotero 插件