Abstract
Objectives. Colorectal cancer is one of the most common malignancies. Recent studies investigated that B7-H4 is highly expressed in various cancers. We aimed at exploring the effect of B7-H4 siRNA on proliferation, invasion, and migration of LOVO cells which expressed B7-H4 notably. Design and Methods. Colon adenocarcinoma dataset was downloaded from The Cancer Genome Atlas. 35 colorectal cancer patients admitted to Shanghai Tongren Hospital were enrolled in this study. Cell proliferation and cell cycle distribution were identified by CCK8 and flow cytometry, respectively. Transwell assay was performed to detect the invasion and migration of LOVO cells. CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were determined by real-time PCR and western blot. Results. B7-H4 expressed is elevated in colorectal cancer tissues than in the adjacent normal tissues. B7-H4 siRNA effectively inhibited the proliferation at 24 h and 48 h, arrested cell cycle at G0/G1, and suppressed cell invasion and migration. Gene set enrichment analysis showed that CXCL12/CXCR4 and JAK/STAT were correlative with the B7-H4 expression. Additionally, CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were reduced. Conclusions. B7-H4 siRNA can effectively inhibit proliferation, invasion, and migration of LOVO cells by targeting CXCL12/CXCR4 and JAK2/STAT3 signaling, which can serve as a new target for colorectal carcinoma treatment.
Highlights
Colorectal cancer is one of the most common malignancies encountered in the world and is the second most common cause of cancer-related mortality [1, 2]
To gain further insight into the biological pathways involved in colorectal cancer pathogenesis through B7-H4 pathway, a gene set enrichment analysis (GSEA) was performed
The gene expression data were obtained at The Cancer Genome Atlas website (TCGA, https://tcga-data.nci.nih.gov/tcga/) for the colon adenocarcinoma (COAD) projects
Summary
Colorectal cancer is one of the most common malignancies encountered in the world and is the second most common cause of cancer-related mortality [1, 2]. B7-H4 is a newly discovered transmembrane protein of the B7-CD28 family It is expressed in human tissues in the cancers of the colon, lung, pancreas, brain, stomach, breast, ovary, esophagus, prostate, liver, and kidney [5,6,7], which is classified as coinhibitors of cell-mediated immunity [5]. It combines with surface receptors of the activated T cell, negatively regulating T cells’ growth, cell cycle, and immune function. To gain further insight into the biological pathways involved in colorectal cancer pathogenesis through B7-H4 pathway, a gene set enrichment analysis (GSEA) was performed
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