MicroRNA-155-5p suppresses PD-L1 expression in lung adenocarcinoma

FEBS Open Bio. 2020 Jun;10(6):1065-1071. doi: 10.1002/2211-5463.12853. Epub 2020 Apr 22.

Abstract

MiR-155-5p is a key oncogenic microRNA that maintains immune homeostasis and mediates cross-talk between inflammation and tumorigenesis. High expression of programmed death ligand-1 (PD-L1) also plays an important role in immune tolerance in tumors. The present study aimed to explore the relationship between miR-155-5p and PD-L1 in lung adenocarcinoma (LUAD) cells A549 and H1650. The expression levels of miR-155-5p and PD-L1 in LUAD patients were detected by a quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and mimics of miR-155-5p were used to model increased expression in A549 or H1650 cells. After 24 h, we measured levels of PD-L1 by qRT-PCR, western blotting and flow cytometry. In addition, we identified two sites in the PD-L1 3'-UTR (5'-AGCAUUA-3' and 5'-GCAUUAA-3') that can be bound by miR-155-5p using TargetScan (http://www.targetscan.org). Compared to normal tissue, miR-155-5p was overexpressed in tumor tissue (P = 0.0456), whereas the expression of PD-L1 was not significantly different (P = 0.1349). The expression levels of miR-155-5p and PD-L1 were negatively correlated (r = -0.6409, P = 0.0459 and r = -0.7544, P = 0.0117). Exogenous overexpression of miR-155-5p decreased the mRNA, total protein and membrane protein expression levels of PD-L1 both in A549 and H1650 cells (P < 0.05). Taken together, our data suggest that miR-155-5p may suppress the expression of PD-L1 in LUAD.

Keywords: MiR-155-5p; PD-L1; lung adenocarcinoma; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / immunology
  • Adenocarcinoma of Lung / pathology
  • B7-H1 Antigen / genetics*
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Lung / pathology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • MicroRNAs / metabolism*
  • Tumor Escape / genetics

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • MIRN155 microRNA, human
  • MicroRNAs