An extensive study of the mechanism of prostate cancer metastasis

Abstract

The study aimed to identify the pivotal genes and pathways involved in prostate cancer metastasis. Using the expression profile dataset GSE7930, downloaded from the Gene Expression Omnibus (GEO) database, differentially expressed genes (DEGs) between primary and highly metastatic prostate cell samples were screened, followed by functional analysis and tumor associated genes (TAG) screening. Protein-protein interaction (PPI) network of DEGs was constructed and module analysis was performed. The expression of DEGs and pathway related genes were evaluated by PCR analysis and the migra- tion ability of prostate tumor cells was observed after FABP4-siRNA blocking. Upregulated FABP4 and GK were signifi- cantly enriched in the PPAR signaling pathway, whereas downregulated IGFBP3 and THBS1 were involved in p53 signaling pathway. Among the identified DEGs, 4 downregulated genes (IGFBP3, NPP4B, THBS1, and PCDH1) and 2 upregulated genes (GJA1 and TUSC3) were TAGs. The module was associated with focal adhesion, ECM-receptor interaction, p53 signaling, and gap junction pathways with the hub node GJA1. After FABP4 silencing by siRNAs in LNcap and metastatic DU-145 cells, the numbers of migrated cells were all significantly declined. The expressions of IGFBP3, TP53 and PPAR were significantly lower in DU-145 cells than in LNcap cells. In conclusion, FABP4, IGFBP3, THBS1, and GJA1 were determined to be potential markers of prostate cancer cell metastasis, and P53, PPAR and gap junction pathways were found to play important roles in prostate cancer cell metastasis. This study may provide helpful guidelines for clinical management.

FABP4 deactivates NF‐κB‐IL1α pathway by ubiquitinating ATPB in tumor‐associated macrophages and promotes neuroblastoma progression

“…However, the upregulated genes of macrophages with FABP4 overexpression was significantly enriched in the ECMreceptor interaction pathway (Figure S4A), which plays a role in cell-substrate junction and has been reported closely related to cancer metastases. 27 Moreover, RNA sequencing and flow analysis results showed that FABP4 knockdown in macrophages increased the expressions of CD80 and CCR7 (pro-inflammatory macrophage marker), but decreased the expressions of CD209 and CD36 (anti-inflammatory macrophage marker), which were all widely expressed on the surface of macrophages. Conversely, FABP4 overexpression exerted the opposite effects (Figure S4C).…”

High expression of ladinin-1 (LAD1) predicts adverse outcomes: a new candidate docetaxel resistance gene for prostatic cancer (PCa)

“…Consistent with previous studies, most of the DEGs (such as IGFBP3 [ 19 ], ITGB3 [ 21 ], ZEB1 [ 22 ], GJA1 [ 23 ], MMP14 [ 24 ], GLI2 [ 25 ], AREG [ 26 ], LCN2 [ 27 ], MACC1 [ 28 ], GALNT3 [ 29 ] and NCOA1 [ 30 ]) were involved in a wide spectrum of processes in tumorigenesis and tumor progression, such as the self-renewal of cancer stem cell, the invasion and metastasis. Interestingly, many of these DEGs (such as IGFBP3 [ 31 ], ITGB3 [ 32 ], ZEB1 [ 33 ], GJA1 [ 34 ], MMP14 [ 35 ], GLI2 [ 36 ] and NCOA1 [ 37 ]) were previously reported to contribute to PCa progression. It is worth noting that certain genes (such as IGFBP3 [ 38 ], GJA1 [ 39 ]) have been implicated in docetaxel treatment efficacy.…”

Identification of critically carcinogenesis-related genes in basal cell carcinoma

“…COL6A1, COL6A2, COL6A3, COL5A2, and COL11A1 are members of the collagen family, and these five genes are enriched in the pathway of “ECM–receptor interaction”, which leads to a direct or indirect control of cellular activities such as adhesion, migration, differentiation, proliferation, and apoptosis. Accumulating evidence indicated that the “ECM–receptor interaction” pathway served as a critical role in the carcinogenesis and metastasis of human cancers, such as prostate cancer, 33 breast cancer, 34 and colorectal cancer. 35 In this study, we also screened “ECM–receptor interaction” as an important pathway by module analysis, which indicated the potential role in the pathogenesis of BCC.…”