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

Oncol Rep. 2021 Jan;45(1):309-316. doi: 10.3892/or.2020.7839. Epub 2020 Nov 6.

Abstract

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.

Keywords: SLCO1B3; non‑small cell lung cancer; epithelial‑mesenchymal transition; E‑cadherin; anchorage‑independent cell growth; migration; invasion.

MeSH terms

  • A549 Cells
  • Animals
  • Carcinoma, Non-Small-Cell Lung / etiology
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Lung Neoplasms / etiology
  • Lung Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Solute Carrier Organic Anion Transporter Family Member 1B3 / physiology*

Substances

  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3