SLC12A8 plays a key role in bladder cancer progression and EMT

Abstract

Bladder cancer is the most common malignant tumor of the urinary system. The intention of the present research is to explore the prognostic value and biological function of solute carrier family 12 member 8 (SLC12A8) in bladder cancer. The analysis based on the TCGA and ONCOMINE database revealed that the expression of SLC12A8 in bladder cancer was notably increased compared with the normal group. SLC12A8 expression was notably correlated with the age, pathological stage, T-stage, and lymph node metastasis of bladder cancer patients. Moreover, the patients’ overall survival was notably shorter in the high SLC12A8 group. Compared with the control, SLC12A8 upregulation enhanced the proliferative, invasive, and migratory capacities of bladder cancer cells and promoted the expression of epithelial–mesenchymal transition (EMT) protein markers including β-catenin, vimentin, snail, and slug, while reduced the expression of E-cadherin. In the case of downregulated SLC12A8 expression, the proliferative, invasive, and migratory capacities of bladder cancer cells and the expression of EMT protein markers presented the opposite trend. This study demonstrated that SLC12A8 was highly correlated with oncogenesis and progression of bladder cancer, indicating that SLC12A8 may be a meaningful biomarker for initial diagnosis and early treatment of bladder cancer.

Comprehensive Analysis of the Oncogenic, Genomic Alteration, and Immunological Landscape of Cation-Chloride Cotransporters in Pan-Cancer

“…Studies have also found that NKCC1 is related to interneurons in the brain ( 39 , 40 ) and plays a certain role in controlling epilepsy ( 38 , 41 ). The regulatory role of solute carrier family 12 members in tumor progression and immune responses has been rarely reported, and recent studies have found that SLC12A8 plays a critical role in bladder cancer progression and EMT ( 42 ). Some new studies believe that NKCC1 is an essential ion cotransporter in the progression of glioma ( 43 ).…”

Comprehensive analysis of Six2-mediated transcriptional regulatory network in ccRCC

“…SLC12A8 and SLC47A1 belong to solute carrier families which regulate the transport of metal-containing anticancer drugs. It was proved that SLC12A8 overexpression could promote cell migration and invasion and may contribute positively to EMT and tumor metastasis [42]. For SLC47A1 (MATE1), recent research found that silence of MATE1 triggered by KRAS mutation could enhance intracellular metformin concentration and improve survival in metastatic colorectal cancer patients, which indicates targeting MATE1 may improve the therapeutic effect of metformin [43].…”

Predictive Value of the Log Odds of Negative Lymph Nodes/T Stage as a Novel Prognostic Factor in Bladder Cancer Patients After Radical Cystectomy

“…There was no statistical difference in the clinical variables between the primary cohort and internal validation cohort. Among all BLCA patients receiving RC, the median ELN, NLN and LONT count (IQR) were 14 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), 13 (7-23) and 0.7 (0.5-1.0), respectively. The majority of them were between 63 and 76 years old (44.6%), male (66.7%), white (86.8%) and married (61.1%).…”

“…In fact, the T stage is a powerful risk factor for BLCA and represents the major tumor features. An increasing number of studies have suggested that T stage is closely associated with prognosis and tumor biological features (13)(14)(15). T stage can represent the biological characteristics of tumor.…”