microRNA‑577 inhibits cell proliferation and invasion in non‑small cell lung cancer by directly targeting homeobox A1

Mol Med Rep. 2019 Mar;19(3):1875-1882. doi: 10.3892/mmr.2019.9804. Epub 2019 Jan 2.

Abstract

An increasing number of studies have indicated that the dysregulation of microRNAs (miRNAs/miR) is closely associated with non‑small cell lung cancer (NSCLC) development and progression by acting as tumor suppressors or oncogenes. Therefore, an in‑depth understanding of the biological roles of miRNAs in NSCLC may provide novel therapeutic methods for the treatment of patients with this disease. In the present study, reverse transcription‑quantitative polymerase chain reaction was used to detect miR‑577 expression in NSCLC tissues and cell lines. Cell Counting Kit‑8 and Transwell invasion assays were performed to determine the effects of miR‑577 on NSCLC cell proliferation and invasion. Luciferase reporter assays were used to demonstrate the relationship between miR‑577 and homeobox A1 (HOXA1) in NSCLC cells. The results revealed that miR‑577 was markedly downregulated in NSCLC tissues and cell lines. Additionally, restoration of miR‑577 expression significantly decreased the proliferation and invasion of NSCLC cells. Furthermore, miR‑577 negatively regulated HOXA1 expression in NSCLC cells by directly binding to its 3'‑untranslated region. HOXA1 was significantly upregulated in NSCLC tissues, and its upregulation was inversely correlated with miR‑577. Notably, restored HOXA1 expression abrogated the reduced proliferation and invasion of NSCLC cells caused by miR‑577 overexpression. Taken together, these results indicated that miR‑577 may have served tumor suppressive roles in NSCLC by directly targeting HOXA1. Therefore, this miRNA may be developed as a potential therapeutic target for the therapy of patients with NSCLC.

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / metabolism*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Transcription Factors / metabolism*
  • Up-Regulation / genetics

Substances

  • Homeodomain Proteins
  • MIRN577 microRNA, human
  • MicroRNAs
  • Transcription Factors
  • homeobox A1 protein