Apolipoprotein C1 (APOC1) promotes tumor progression via MAPK signaling pathways in colorectal cancer
Received 28 October 2018
Accepted for publication 28 February 2019
Published 29 May 2019 Volume 2019:11 Pages 4917—4930
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Beicheng Sun
Hui Ren,1,2,* Zhihui Chen,1,* Liang Yang,1,* Weixin Xiong,1 Hong Yang,3 Kaiwu Xu,1 Ertao Zhai,1 Li Ding,4 Yulong He,1,2 Xingming Song1
1Department of Gastrointestinal Surgery Centre, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Center for Digestive Disease, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Department of Operating Room, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Pathology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
*These authors contributed equally to this work
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.
Keywords: apolipoprotein C1, APOC1, colorectal cancer, prognosis, MAPK signaling
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