Identification of the Effects of Chondroitin Sulfate on Inhibiting CDKs in Colorectal Cancer Based on Bioinformatic Analysis and Experimental Validation

Abstract

With a high occurrence rate and high mortality, the treatment of colorectal cancer (CRC) is increasingly attracting the attention of scholars. Hub genes that determine the phenotypes of CRC become essential for targeted therapy. In the present study, the importance of cyclin-dependent kinases (CDKs) on the occurrence of CRC was identified by data mining of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The results showed that the gene expression levels of CDK1, CDK4, and CDK6 were obviously changed in different stages of CRC. Among the CDKs, CDK4 was suggested as an independent risk factor for CRC based on Cox analysis. Furthermore, chondroitin sulfate (CS), a kind of dietary supplement to treat osteoarthritis, was predicted to treat CRC based on its chemical structure and GEO datasets. Cell assay experiments with the human CRC cell line HCT-116 also verified this prediction. CS inhibited the gene and protein expression levels of CDKs and increased the ratios of apoptotic or dead HCT-116 cells by regulating mitogen-activated protein (MAP) kinase pathways. Our data highlight the essential roles of CDKs in CRC carcinogenesis and the effects of CS on treating CRC, both of which will contribute to the future CRC treatment.

Sturgeon Chondroitin Sulfate Restores the Balance of Gut Microbiota in Colorectal Cancer Bearing Mice

“…Kantor et al (2016) found that CS supplementation may be directly associated with reducing the risk of CRC [ 12 ]. Zhou et al (2021) analyzed data from the Cancer Genome Atlas (TCGA) and gene expression synthesis (GEO), and determined that CS can increase apoptosis in HCT-116 cells [ 13 ]. Our previous studies have shown that sturgeon derived chondroitin sulfate (SCS) can inhibit the tumor growth of colorectal cancer in mice [ 14 ].…”

Sulfation of chondroitin and bile acids converges to antagonize Wnt/β-catenin signaling and inhibit APC deficiency-induced gut tumorigenesis

“…Chondroitin is a sulfation substrate 33 . CS, a widely used dietary supplement to treat osteoarthritis, was suggested to inhibit CRC based on some experimental and epidemiological evidence, but without a defined mechanism 34 , 35 . As expected, and as a result of sulfation inhibition, the content of CS was markedly reduced in the intestine and colon of tumor-bearing Apc Δgut-Het Papss2 Δgut mice ( Fig.…”

Detection and assessment of immune and stromal related risk genes to predict preeclampsia: A bioinformatics analysis with dataset

“…Growing evidence suggests that preeclampsia constitutes a severe gestational disorder characterized by pronounced inflammation within the maternal body, disrupting the functionality of the monocyte-macrophage system. [25] Immune cell infiltration analysis is a cutting-edge bioinformatic technique used to explore the diagnosis and prognosis of various diseases, including bladder, [26] breast, [27] colorectal, [28] and ovarian. [29] While numerous studies have diligently pursued molecular markers for diagnosing and treating PE through data exploration and analysis in databases like GEO, exploration of the immune and stromal cell infiltration landscape in PE and the molecular typing of immunomarkers remains unexplored.…”