MiR-23b functions as an oncogenic miRNA by downregulating Mcl-1S in lung cancer cell line A549

J Biochem Mol Toxicol. 2020 Jul;34(7):e22494. doi: 10.1002/jbt.22494. Epub 2020 Apr 13.

Abstract

It has been reported that microRNA-23b (miR-23b) plays a role in multiple cancers, while its impact on lung cancer has not been comprehensively known. Our study explored the probable impacts of miR-23b on lung cancer cells. Expression of miR-23b was assessed by reverse transcription quantitative polymerase chain reaction. After miR-23b mimic, inhibitor, and their own control were transfected into A549 cells, cell viability, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) were investigated through different experimental methods. The targeting contact between miR-23b and myeloid cell leukemia-1 (Mcl-1) was investigated applying dual-luciferase activity assay. In addition, the modulatory impacts of miR-23b on the splicing variants of Mcl-1 (Mcl-1S and Mcl-1L) were explored. MiR-23b was highly expressed in lung cancer cells compared with normal lung cells. Increased expression of miR-23b promoted A549 cell viability, migration, invasion, and EMT. However, miR-23b silencing produced the opposite results. Mcl-1 has been proven to be a specialized target of miR-23b. Compared with the reduction of Mcl-1S induced by miR-23b overexpression, Mcl-1L showed negligible interaction with miR-23b. Moreover, the antitumor activities of miR-23b silencing were alleviated by Mcl-1S silencing. The blockage of Janus kinase/signal transducer and activator of transcription protein (JAK/STAT) and Wnt/β-catenin induced by miR-23b silencing was reversed by Mcl-1S silencing. MiR-23b might be an up-and-coming biomarker of lung cancer. In addition, miR-23b was involved in the tumor-promoting effects and the mobilization of JAK/STAT and Wnt/β-catenin pathways through the reduction of Mcl-1S.

Keywords: Mcl-1; NSCLC; miR-23b.

MeSH terms

  • A549 Cells
  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis / genetics*
  • Cell Movement / genetics
  • Cell Survival / genetics
  • Down-Regulation / genetics*
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Janus Kinases / metabolism
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism*
  • Neoplasm Invasiveness / genetics
  • STAT Transcription Factors / metabolism
  • Transfection
  • Wnt Signaling Pathway / genetics

Substances

  • Biomarkers, Tumor
  • MCL1 protein, human
  • MIRN23b microRNA, human
  • MicroRNAs
  • Myeloid Cell Leukemia Sequence 1 Protein
  • STAT Transcription Factors
  • Janus Kinases