SLC7A5 Promotes Colorectal Cancer Progression by Regulating Cell Cycle and Migration

Abstract

Background: Solute carrier family 7 member 5 (SLC7A5) was identified highly expressed and as a key participant in various tumor development; however, the role it played in colorectal cancer remains unclear. Methods and Results: In the current study, the expression of SLC7A5 were systematically mined in public databases and validated by real-time PCR in colon cancer and normal tissues. And then, the co-expression and pathway analysis got from public database, which indicated the potential influence of SLC7A5 for the etiology of colorectal cancer, were evaluated in the colon cancer cell lines by loss of SLC7A5 function experiment, flow cytometry, western blot, and wound healing assay. The results showed that the mRNA expression of SLC7A5 was significantly higher in colorectal cancer tissues than that in the non-tumor controls for GEO and TCGA datasets as well as 40 pairs of Xiangya clinical samples. The functional enrichment analysis based on public database showed that the pathways enriched most were cell cycle and epithelial-to-mesenchymal transition (EMT), and Cyclin D1 (CCND1) were the only gene that had a significant positive correlation with SLC7A5. Loss of SLC7A5 function in colon cancer cell lines could arrest cell cycle at G1 phase by down-regulating CCND1 and CDK2 protein expression, and may reduce cell migration by reversing EMT though upregulation of E-Cadherin and downregulation of zonula occludens-1. Conclusion: SLC7A5 is likely associated with the progression of colon cancer.

Reanalysis of DIA Data Demonstrates the Capabilities of MS/MS-Free Proteomics to Reveal New Biological Insights in Disease-Related Samples

“…The protein Q6YN16 (hydroxysteroid dehydrogenase-like protein 2 -HSDL2) is involved in fatty acid metabolism and is well associated with the progression of various types of cancer. 45,46 For example, it has been shown that in various types of gliomas, overexpression of this protein induces proliferation and increases cell survival, while gene knockdown leads to apoptosis and cell cycle arrest. 47 In contrast to the previous study, a recent report demonstrated that knockdown of HSDL2 led to inhibition of ferroptosis in cholangiocarcinoma cells, thereby promoting cancer progression.…”

Acidic ascites inhibits ovarian cancer cell proliferation and correlates with the metabolomic, lipidomic and inflammatory phenotype of human patients

“…Glutamine is required to produce glutathione that removes ROS and rescues the cancer cells from oxidative stress-induced apoptosis since ROS is produced by cancer cells due to an increased metabolic rate, gene mutation, and relative hypoxia [39]. Moreover, BCAAs are utilized to synthesize glutamate and glutathione and lead to therapeutic resistances following overexpression of SLC7A5, a BCAA transporter observed in pancreatic, colorectal, gastric, and OC cells [40][41][42]. Therefore, OC patients with stage IV may be highly Myc-driven and then overexpressed ASCT2 and SLC7A5 to promote glutamine homeostasis.…”

SLC38A3 Promotes the Proliferation and Migration of Tumor Cells and Predicts Poor Prognosis in Colorectal Cancer

“…In addition, the role of SLC7A5 , SLC9A3 , ABCC2 , ABCG2 , etc. in the invasion and progression of CRC has been reported. − Nevertheless, current research on the molecular mechanisms by which these transporters impact CRC, as well as their potential application as drug targets in clinical treatment, remains insufficient. Here, we performed a comprehensive bioinformatics analysis to identify differentially expressed transporter protein-related genes (DE-TPRGs) in CRC and determine their potential functions involved in CRC progression.…”