Apolipoprotein C1 (APOC1) promotes tumor progression via MAPK signaling pathways in colorectal cancer

被引:54
作者
Ren, Hui [1 ,2 ]
Chen, Zhihui [1 ]
Yang, Liang [1 ]
Xiong, Weixin [1 ]
Yang, Hong [3 ]
Xu, Kaiwu [1 ]
Zhai, Ertao [1 ]
Ding, Li [4 ]
He, Yulong [1 ,2 ]
Song, Xingming [1 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg Ctr, 58 Zhongshan 2nd Rd, Guangzhou 510080, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 7, Ctr Digest Dis, Shenzhen, Peoples R China
[3] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Operating Room, Guangzhou, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Pathol, Guangzhou, Guangdong, Peoples R China
来源
CANCER MANAGEMENT AND RESEARCH | 2019年 / 11卷
关键词
apolipoprotein C1; APOC1; colorectal cancer; prognosis; MAPK signaling; DENSITY-LIPOPROTEIN RECEPTOR; GENE-EXPRESSION; KINASE PATHWAYS; TRANSGENIC MICE; CELLS; IDENTIFICATION; APOPTOSIS; BIOMARKER; ACTIVATION; INVASION;
D O I
10.2147/CMAR.S192529
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Aim: Identifying high-efficiency prognostic markers for colorectal cancer (CRC) is necessary for clinical practice. Increasing evidence demonstrates that apolipoprotein C1 (APOC1) promotes carcinogenesis in some human cancers. However, the expression status and biological function of APOC1 in CRC remain unclear. Materials and methods: We detected the association between APOC1 expression and clinicopathological features in 140 CRC patients by immunohistochemistry. Small interfering RNA (siRNA) technology was used to downregulate APOC1 expression in CRC cells. Cell proliferation was estimated by CCK8 and clonogenic assays. The cell cycle and apoptosis were analyzed by flow cytometry. Cell migration and invasion were examined by a transwell assay. Gene set enrichment analysis (GSEA) and protein expression of signaling pathways were used to suggest the possible APOC1-associated pathways in CRC. Results: APOC1 was highly expressed in CRC tissues. High immunohistochemistry (IHC) expression of APOC1 was correlated with the N stage, M stage and TNM stage. High IHC APOC1 expression in CRC tissues was associated with poor prognosis. Univariate and multivariate Cox regression analyses showed that APOC1 was an independent risk factor for OS. Cell proliferation of CRC cell lines was inhibited by the downregulation of APOC1. Moreover, si-APOC1 transfection induced cell cycle arrest but low apoptosis increases by regulating the expression of related proteins. Cell migration and invasion were also inhibited by the downregulation of APOC1. The Cancer Genome Atlas Colorectal Adenocarcinoma (TCGA COAD-READ) dataset analyzed by GSEA showed that APOC1 might be involved in the mitogen-activated protein kinase (MAPK) signaling pathway, which was further preliminarily confirmed by Western blotting. Conclusion: APOC1 was overexpressed in CRC tissues, and a high level of APOC1 contributed to a poor prognosis. APOC1 expression influenced the cell proliferation ability and motility capacity of CRC via the MAPK pathway. APOC1 could act as a novel prognostic biomarker in CRC.
引用
收藏
页码:4917 / 4930
页数:14
相关论文
共 47 条
  • [31] Colorectal cancer statistics, 2017
    Siegel, Rebecca L.
    Miller, Kimberly D.
    Fedewa, Stacey A.
    Ahnen, Dennis J.
    Meester, Reinier G. S.
    Barzi, Afsaneh
    Jemal, Ahmedin
    [J]. CA-A CANCER JOURNAL FOR CLINICIANS, 2017, 67 (03) : 177 - 193
  • [32] Modeling Oncogenic Signaling in Colon Tumors by Multidirectional Analyses of Microarray Data Directed for Maximization of Analytical Reliability
    Skrzypczak, Magdalena
    Goryca, Krzysztof
    Rubel, Tymon
    Paziewska, Agnieszka
    Mikula, Michal
    Jarosz, Dorota
    Pachlewski, Jacek
    Oledzki, Janusz
    Ostrowsk, Jerzy
    [J]. PLOS ONE, 2010, 5 (10):
  • [33] Role of MAPK in apolipoprotein CIII-induced apoptosis in INS-1E cells
    Sol, E-ri M.
    Sundsten, Tea
    Bergsten, Peter
    [J]. LIPIDS IN HEALTH AND DISEASE, 2008, 8 (1)
  • [34] Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
    Subramanian, A
    Tamayo, P
    Mootha, VK
    Mukherjee, S
    Ebert, BL
    Gillette, MA
    Paulovich, A
    Pomeroy, SL
    Golub, TR
    Lander, ES
    Mesirov, JP
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (43) : 15545 - 15550
  • [35] GSEA-P:: A desktop application for Gene Set Enrichment Analysis
    Subramanian, Aravind
    Kuehn, Heidi
    Gould, Joshua
    Tamayo, Pablo
    Mesirov, Jill P.
    [J]. BIOINFORMATICS, 2007, 23 (23) : 3251 - 3253
  • [36] Identification of Apolipoprotein C-I Peptides as a Potential Biomarker and its Biological Roles in Breast Cancer
    Sun, Yadong
    Zhang, Junjie
    Guo, Fei
    Zhao, Wei
    Zhan, Yuxiao
    Liu, Chenyu
    Fan, Yuxia
    Wang, Jiaxiang
    [J]. MEDICAL SCIENCE MONITOR, 2016, 22 : 1152 - 1160
  • [37] Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells
    Takano, S.
    Yoshitomi, H.
    Togawa, A.
    Sogawa, K.
    Shida, T.
    Kimura, F.
    Shimizu, H.
    Tomonaga, T.
    Nomura, F.
    Miyazaki, M.
    [J]. ONCOGENE, 2008, 27 (20) : 2810 - 2822
  • [38] Downregulation of ZNF278 arrests the cell cycle and decreases the proliferation of colorectal cancer cells via inhibition of the ERK/MAPK pathway
    Tian, Xiao-Qing
    Guo, Fang-Fang
    Sun, Dan-Feng
    Wang, Ying-Chao
    Yang, Li
    Chen, Sheng-Liang
    Hong, Jie
    Fang, Jing-Yuan
    [J]. ONCOLOGY REPORTS, 2017, 38 (06) : 3685 - 3692
  • [39] Silencing expression of the clusterin/apolipoprotein J gene in human cancer cells using small interfering RNA induces spontaneous apoptosis, reduced growth ability, and cell sensitization to genotoxic and oxidative stress
    Trougakos, IP
    So, A
    Jansen, B
    Gleave, ME
    Gonos, ES
    [J]. CANCER RESEARCH, 2004, 64 (05) : 1834 - 1842
  • [40] Neurodegenerative and physiological actions of c-Jun N-terminal kinases in the mammalian brain
    Waetzig, V
    Herdegen, T
    [J]. NEUROSCIENCE LETTERS, 2004, 361 (1-3) : 64 - 67