Insulin-Like Growth Factor Binding Protein 5—A Probable Target of Kidney Renal Papillary Renal Cell Carcinoma

Abstract

Kidney renal papillary renal cell carcinoma (KIRP) accounts for 10–15% of renal cell carcinoma (RCC). The need to find more therapeutic targets for KIRP is urgent because most targeted drugs have limited effects on advanced KIRP. Insulin-like growth factor (IGF) binding protein 5 (IGFBP5) is a secreted protein related to cell proliferation, cell adhesion, cell migration, the inflammatory response and fibrosis; these functions are independent of IGF. In our study, we determined the expression and functions of IGFBP5 with data from the database of The Cancer Genome Atlas (TCGA). We found that IGFBP5 is down regulated in KIRP kidney tissues compared to its expression in control tissues and that the expression of IGFBP5 is negatively related to patient survival. Bioinformatic analysis showed the probable processes and pathways involved in altered IGFBP5 expression, including blood vessel development, the cellular response to growth factor stimulus, the response to transforming growth factor β (TGF-β), and extracellular matrix organization. We proposed that VEGFA and TGF-β act as upstream regulatory factors of IGFBP5 and verified this in the Caki-2 cell line. Based on our results, we suggest that IGFBP5 might be a therapeutic target of KIRP.

Downregulation of IGFBP5 contributes to replicative senescence via ERK2 activation in mouse embryonic fibroblasts

“…Upregulation of IGFBP5 in senescent HUVECs was confirmed in the present study ( Supplementary Figure 7D ). However, as in MEFs in the present study, suppression of proliferation by IGFBP5 knockdown was also observed in human tumor cells [ 50 , 51 ] and non-tumor cells [ 52 , 53 ], while the opposite was observed in several lines of cancer cells [ 54 , 55 ]. Therefore, it seems that the role of IGFBP5 in cellular senescence or cell proliferation may vary depending on the cell type, though additional work is required to clarify this issue.…”

A Dynamic Transcriptome Map of Different Tissue Microenvironment Cells Identified During Gastric Cancer Development Using Single-Cell RNA Sequencing

“…EndC4 is mainly expressed in the tumors stage the main function of MYC targeting and EMT protein secretion signatures, suggesting this cluster exhibited a high proliferation phenotype and was crucial to GC genesis and progression. IGFBP5 is a new marker gene identified in this cluster; it is a secreted protein related to cell adhesion, proliferation, migration, inflammatory mediators, and fibrosis ( 68 ). A recent study reported that IGFBP5 was highly expressed in a variety of cancers, promoted cancer occurrence and development, and was implicated in radiotherapy and chemotherapy resistance ( 69 ), but its significance in endothelial cells warrants further research.…”

Construction of a prognostic value model in papillary renal cell carcinoma by immune-related genes

“…Because of the different molecular mechanisms and the low proportion of PRCC in RCC, patients with PRCC have been excluded from large clinical trials of targeted drugs, such as sorafenib and sunitinib, and research on PRCC is always less studied than clear cell RCC and progresses slowly. [21] Although some patients with PRCC can be diagnosed by ultrasonography and receive surgery at an early stage, a significant number of advanced patients die due to postoperative recurrence, metastasis, and resistance to chemotherapeutic drugs, underscoring the importance of exploring the molecular mechanisms and prognostic factors of PRCC. [22] …”