MicroRNA‑718 serves a tumor‑suppressive role in non‑small cell lung cancer by directly targeting CCNB1

Int J Mol Med. 2020 Jan;45(1):33-44. doi: 10.3892/ijmm.2019.4396. Epub 2019 Nov 4.

Abstract

MicroRNA‑718 (miR‑718) serves crucial roles in tumorigenesis and in the progression of a number of cancers. However, the expression profile, specific functions and mechanisms of action of miR‑718 in non‑small cell lung cancer (NSCLC) are still elusive. The aims of the present study were to quantify the expression of miR‑718, determine its biological roles and elucidate the molecular mechanisms responsible for its activities in NSCLC cells. Reverse transcription‑quantitative PCR was carried out to assess miR‑718 expression in NSCLC tissue samples and cell lines. The Cell Counting Kit‑8 assay, flow cytometry, cell migration and invasion assays, and a tumor xenograft experiment were performed to evaluate the effects of miR‑718 overexpression on the malignant biological behaviors of NSCLC cells. miR‑718 expression was demonstrated to be significantly decreased in NSCLC tissue samples and cell lines. This reduced expression was significantly associated with tumor, node, metastasis stage, tumor size, lymph node metastasis and poor overall survival among patients with NSCLC. Exogenous miR‑718 expression suppressed NSCLC cell proliferation, migration and invasion, and promoted apoptosis in vitro; whereas it hindered tumor growth in vivo. Experiments to elucidate the mechanisms involved revealed that miR‑718 functions by directly targeting cyclin B1 (CCNB1) mRNA. CCNB1 expression was found to be upregulated in NSCLC and inversely correlated with miR‑718 levels. CCNB1 depletion had effects similar to those of miR‑718 overexpression in NSCLC cells. Furthermore, restoration of CCNB1 expression attenuated the tumor‑suppressive effects of miR‑718 overexpression in NSCLC cells. These results indicated that miR‑718 suppressed NSCLC progression in vitro and in vivo by directly targeting CCNB1 mRNA, which may indicate a potential target for the diagnosis and treatment of this fatal disease.

Publication types

  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Cyclin B1 / genetics*
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Genes, Tumor Suppressor*
  • Humans
  • Immunophenotyping
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • RNA Interference*
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • CCNB1 protein, human
  • Cyclin B1
  • MIRN718 microRNA, human
  • MicroRNAs