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
  • [1] [Anonymous], PLOS ONE
  • [2] Glycation of Apolipoprotein C1 Impairs Its CETP Inhibitory Property: Pathophysiological Relevance in Patients With Type 1 and Type 2 Diabetes
    Bouillet, Benjamin
    Gautier, Thomas
    Blache, Denis
    de Barros, Jean-Paul Pais
    Duvillard, Laurence
    Petit, Jean-Michel
    Lagrost, Laurent
    Verges, Bruno
    [J]. DIABETES CARE, 2014, 37 (04) : 1148 - 1156
  • [3] Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer
    Budinska, Eva
    Popovici, Vlad
    Tejpar, Sabine
    D'Ario, Giovanni
    Lapique, Nicolas
    Sikora, Katarzyna Otylia
    Di Narzo, Antonio Fabio
    Yan, Pu
    Hodgson, John Graeme
    Weinrich, Scott
    Bosman, Fred
    Roth, Arnaud
    Delorenzi, Mauro
    [J]. JOURNAL OF PATHOLOGY, 2013, 231 (01) : 63 - 76
  • [4] Apolipoprotein C-I plays a role in the pathogenesis of glomerulosclerosis
    Bus, Pascal
    Pierneef, Louise
    Bor, Rosalie
    Wolterbeek, Ron
    van Es, Leendert A.
    Rensen, Patrick C. N.
    de Heer, Emile
    Havekes, Louis M.
    Bruijn, Jan A.
    Berbee, Jimmy F.
    Baelde, Hans J.
    [J]. JOURNAL OF PATHOLOGY, 2017, 241 (05) : 589 - 599
  • [5] Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases
    Cargnello, Marie
    Roux, Philippe P.
    [J]. MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 2011, 75 (01) : 50 - 83
  • [6] Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2
    Chen, Z
    Cobb, MH
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (19) : 16070 - 16075
  • [7] Identification of serum proteins discriminating colorectal cancer patients and healthy controls using surface-enhanced laser desorption ionisation-time of flight mass spectrometry
    Engwegen, Judith Y. M. N.
    Helgason, Helgi H.
    Cats, Annemieke
    Harris, Nathan
    Bonfrer, Johannes M. G.
    Schellens, Jan H. M.
    Beijnen, Jos H.
    [J]. WORLD JOURNAL OF GASTROENTEROLOGY, 2006, 12 (10) : 1536 - 1544
  • [8] Discovery and identification of potential biomarkers of papillary thyroid carcinoma
    Fan, Yuxia
    Shi, Linan
    Liu, Qiuliang
    Dong, Rui
    Zhang, Qian
    Yang, Shaobo
    Fan, Yingzhong
    Yang, Heying
    Wu, Peng
    Yu, Jiekai
    Zheng, Shu
    Yang, Fuquan
    Wang, Jiaxiang
    [J]. MOLECULAR CANCER, 2009, 8 : 79
  • [9] Fitzmaurice C, 2017, JAMA ONCOL, V3, P524, DOI [10.1001/jamaoncol.2016.5688, 10.1001/jamaoncol.2018.2706]
  • [10] Forman D., 2014, World Cancer Report 2014, P16