Cancer type-SLCO1B3 promotes epithelial-mesenchymal transition resulting in the tumour progression of non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is one of the most common histologically defined subtypes of lung cancer. To identify a promising molecular target for NSCLC therapy, we performed gene expression analysis at the exon level using postoperative specimens of NSCLC patients. Exon array and real-time PCR analyses revealed that an alternative splicing variant of solute carrier organic anion transporter family member 1B3 (SLCO1B3) called cancer type-SLCO1B3 (Ct-SLCO1B3) was significantly upregulated in the NSCLC samples. SLCO1B3 expressed in the liver [liver type (Lt)-SLCO1B3] was found to be localised in the cell membrane, whereas Ct-SLCO1B3 was detected in the cytoplasm of NSCLC cells. RNAi-mediated knockdown of Ct-SLCO1B3 inhibited in vitro anchorage-independent cell growth, cell migration, and in vivo tumour growth of A549 cells. Overexpression of Ct-SLCO1B3 but not Lt-SLCO1B3 upregulated anchorage-independent cell growth and cell migration of NCI-H23 cells. Mechanistically, Ct-SLCO1B3 was found to regulate the expression of epithelial-mesenchymal transition (EMT)-related genes. The upregulation of E-cadherin was discovered to be especially pivotal to phenotypes of Ct-SLCO1B3-suppressed A549 cells. These findings suggest that Ct-SLCO1B3 functions as a tumour-promoting factor via regulating EMT-related factors in NSCLC.

Automated summary

It was found that Ct-SLCO1B3 acts as a tumour-promoting factor in NSCLC by regulating EMT-related genes, leading to upregulation of anchorage-independent cell growth and cell migration.