Calbindin S100A16 Promotes Renal Cell Carcinoma Progression and Angiogenesis via the VEGF/VEGFR2 Signaling Pathway

Abstract

Purpose. Recent research has indicated that the calcium-binding protein S100A16 promotes carcinogenesis and tumor growth in several forms of cancer. e objective of this study was to examine the relationship between S100A16 and renal cell cancer. Methods. By using e Cancer Genome Atlas (TCGA) database, the differentially expressed gene S100A16 was identified, and its appearance and link to the prognosis of persons with renal cancer were confirmed. Cox regression was used in multivariate analysis, and a nomogram was developed for internal validation. e correlation between S100A16 and immune cells was analyzed in the TIMER database. Moreover, the potential mechanism of action was investigated utilizing GO and KEGG enrichment analyses. Proliferation, migration, and angiogenesis were investigated in vitro, and the involvement of S100A16 in the undesirable biological events of renal cell carcinoma (RCC) was further explored. Results. S100A16 was the differentially expressed molecule identified through database screening. Malignant tissues showed higher S100A16 expression than noncancerous tissues, and S100A16 expression was mostly localized in the cytoplasm. According to the TCGA and KM-plotter datasets, patients with RCC and low S100A16 expression had superior OS, PFI, and DSS. e C-index of the nomogram was 0.754 (0.726-0.782), and the accuracy of the prediction model was high. e TIMER database shows that the expression of S100A16 is associated with immune infiltration and may play an important role in promoting tumor cell immune escape in the RCC tumor microenvironment. S100A16 may influence the biological processes of RCC via the VEGF/VEGFR2 signaling route and PI3K-Akt signaling pathway and through P53 alteration and cell cycle according to the gene enrichment technique. In vitro cytological experiments demonstrated that S100A16 knockdown can inhibit the proliferation and migration of renal cancer cells and the expression levels of VEGF, VEGFR2, and phosphorylated AKT within renal cancer cells, thereby inhibiting angiogenesis in renal cancer cells and resulting in a poor prognosis of RCC. Conclusion. A decrease in S100A16 expression may dramatically increase the OS, PFI, and DSS of patients with RCC and may thus be used as a biomarker for predicting RCC. It may be associated with the immune infiltration of RCC and play a crucial role in the immune evasion of tumor cells within the RCC microenvironment. Intervention of s100a16 can promote the progression and angiogenesis of renal cell carcinoma through the VEGF/VEGFR2 signal transduction pathway and lead to poor prognosis of renal cell carcinoma. ese findings suggest a potential target for the development of anticancer strategies for renal cancer.

HIF-1α participates in the regulation of S100A16-HRD1-GSK3β/CK1α pathway in renal hypoxia injury

“…S100A16 is predominantly localized in the cytoplasm of cells, where S100A16 can interact with a variety of target proteins, including signaling molecules and cytoskeletal components. These interactions can modulate cellular processes and affect various signaling pathways [21][22][23]. Some studies have suggested that S100A16 was involved in promoting cell proliferation, metastasis, and tumor growth in certain cancers, including prostate cancer and esophageal squamous cell carcinoma [24].…”

Characterization of the TRPV6 calcium channel-specific phenotype by RNA-seq in castration-resistant human prostate cancer cells

“…Our data suggest that the upregulation of key gene targets under TRPV6 suppression or overexpression indicates that TRPV6 plays a crucial role via calcium signaling in angiogenesis, required for dissemination of prostate cancer cells to both adjacent and distant tissues. Indeed, several studies have reported that calcium signaling in cancer cells was linked to the angiogenic phenotype (Cui et al, 2017;Wang N. et al, 2022) via either the expression of hypoxia-inducible factor 1-alpha (HIF1ɑ) (Kim et al, 2015;Ma et al, 2018) or secretion of the vascular endothelial growth factor (VEGF), or inducing calcium oscillations in endothelial cells while binding to VEGF receptors (Wang N. et al, 2022;, or inducing cell proliferation, migration, and invasion needed to form new vessels. TRP channels, known to be environmental sensors and permeable to calcium, modulate intracellular calcium concentrations and participate in the initiation and progression of cancers Bai et al, 2023).…”

An Update on S100A16 in Human Cancer

“…The authors further demon-strated that knockdown of S100A16 suppressed cell proliferation and invasion abilities in RCC cells. These functional effects were suggested to be associated with inhibition of VEGF, VEGFR2, and pAkt in RCC cells with S100A16 knockdown [32].…”

“…Using the TCGA transcriptome dataset, Wang et al identified S100A16 mRNA to be significantly up-regulated in renal cell carcinoma (RCC) specimens as compared to noncancerous tissues [32]. High expression of S100A16 mRNA in RCC specimens was suggested to be associated with poor overall survival, progression-free interval, and diseasespecific survival.…”