An assessment of the relationship between the expression of CCR7/CCL19 axis and selected regulatory miRNAs in non-small cell lung cancer

Mol Biol Rep. 2019 Oct;46(5):5389-5396. doi: 10.1007/s11033-019-04993-3. Epub 2019 Aug 28.

Abstract

CC chemokine receptor type 7 (CCR7) and its ligands has been implicated in the occurrence and progression of NSCLC. Previous studies have revealed that the diagnostic value of CCR7/CCL19 axis in lung tumorigenesis remains controversial. The present study evaluates the relationship between the mRNA expression of CCR7/CCL19 axis and selected regulatory miRNAs in NSCLC patients. It analyzes the expression level of CCR7 mRNA and its ligand in tumor tissue in relation to expression level of two miRNAs: miR let-7a and miR-335, as transcriptional regulators of study genes. Twenty-seven patients (n = 27) were enrolled. The expression of the studied genes and miRNAs was evaluated by qPCR. Tumour tissue fragments, adjacent macroscopically-unchanged lung tissue (control) and patient serum were used as biological material for study. Elevated expression of CCR7 and CCL19 mRNA was observed in patients with metastasis to lymph nodes. We noticed upregulated miR-335 expression and downregulated miR let-7a expression in patient serum with regard to AJCC tumor staging. Higher miR-335 expression and lower miR let-7a expression level was observed in patients with metastasis to lymph node. The presence of changes observed in the expression level of miR-335 and miR let-7a in the serum of NSCLC patients in relation to lymph node metastases and tumor stage may serve as a non-invasive molecular biomarker of tumor progression; however, this observation requires further investigation.

Keywords: CCL19; CCR7; Lymph node metastasis; Non-small cell lung cancer; Real-time polymerase chain reaction; miRNAs.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Chemokine CCL19 / genetics*
  • Chemokine CCL19 / metabolism
  • Female
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, CCR7 / genetics*
  • Receptors, CCR7 / metabolism
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • CCL19 protein, human
  • CCR7 protein, human
  • Chemokine CCL19
  • MIRN335 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Receptors, CCR7
  • mirnlet7 microRNA, human