Yi Guan, Fei Xiao, Ting Liu, Yan Zeng, Hengcheng Zhu, Kang Yang
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引用次数: 0
Abstract
Objective: SPON2 is an extracellular matrix constituent belonging to the Mindin-F-spondin protein family. Our previous study proved that SPON2 emerges as a novel biomarker in renal fibrogenesis. However, the role of SPON2 in regulation and its impact on RCC progression remains uncertain.
Methods: The TCGA and GEO databases were used to explore the expression of SPON2 in RCC. Western blot was used to detect the expression of SPON2 between RCC and normal samples. Survival analysis and gene set variation analysis were performed to discover the prognostic significance and underlying mechanism of SPON2 in RCC. The role of SPON2 was detected by CCK8, wound healing, invasion, and xenograft model assays. Autophagy-related experiments verified the bioinformatic findings.
Results: Bioinformatic analysis revealed significantly higher SPON2 expression in RCC, which was found to be associated with improved overall survival in patients with high SPON2 levels. Detection of clinical samples revealed an increase in SPON2 expression within the context of ccRCC tissues. In addition, data from in vitro assays revealed that SPON2 overexpression significantly enhanced the proliferative and migratory capacity of cell lines. Xeno-graft experiments demonstrated the accelerated tumor growth effect of SPON2. Mechanistic investigation showed that the PI3K/AKT/mTOR pathway was inhibited by SPON2.
Conclusion: Our data illustrated that SPON2 functions as an oncogene in the tumorigenesis of RCC tumorigenesis, which is accompanied by an inverse relationship between SPON2 expression levels and patient prognosis. The underlying mechanism likely involves the promotion of autophagy by modulating the PI3K/AKT/mTOR pathway.
期刊介绍：
Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes.
Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer.
As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
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