MiR-1471 protects the aggravation of non-small-cell lung carcinoma by targeting FOXL1

Biofactors. 2020 Sep;46(5):734-742. doi: 10.1002/biof.1661. Epub 2020 Oct 12.

Abstract

This study detected the expression pattern of miR-1471 in non-small-cell lung cancer (NSCLC) tissues, and analyzed the prognostic significance of miR-1471 in NSCLC. Subsequently, potential targets of miR-1471 were screened for assessing the potential molecular mechanism in NSCLC. A total of 47 primary NSCLC cases treated by radical resection and systematic lymphadenectomy in the department of thoracic surgery were collected, as well as their clinical data. MiR-1471 levels in NSCLC tissues were detected by quantitative real-time polymerase chain reaction. The prognostic potential of miR-1471 in NSCLC was assessed by Kaplan-Meier method, followed by log-rank test. Potential target genes of miR-1471 and the binding sites were predicted by bioinformatics analysis, and screened for the optimal one. The binding relationship between miR-1471 and the target FOXL1 was examined by dual-luciferase reporter assay. Subsequently, biological functions of miR-1471 and FOXL1 in NSCLC cell functions were explored by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) assay and flow cytometry. MiR-1471 was downregulated in NSCLC tissues and its level was correlated to TNM staging in NSCLC patients. Overall survival was poor in NSCLC patients expressing low level of miR-1471. Overexpression of miR-1471 attenuated proliferative ability and arrested cell cycle progression in G1/S phase. FOXL1 was confirmed to be the target gene binding miR-1471. Its expression pattern and biological functions in NSCLC cells were contrary to those of miR-1471. MiR-1471 is downregulated in NSCLC samples, which is related to TNM staging and prognosis in NSCLC patients. Therefore, miR-1471 suppresses the malignant aggravation of NSCLC via inhibiting the translation of FOXL1 mRNA. In addition, it could be used as an effective biomarker for predicting the prognosis in NSCLC.

Keywords: FOXL1; NSCLC; malignant progression; miR-1471.

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Forkhead Transcription Factors / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics*
  • Middle Aged

Substances

  • FOXL1 protein, human
  • Forkhead Transcription Factors
  • MicroRNAs