miR‑20b promotes growth of non‑small cell lung cancer through a positive feedback loop of the Wnt/β‑catenin signaling pathway

Int J Oncol. 2020 Feb;56(2):470-479. doi: 10.3892/ijo.2019.4940. Epub 2019 Dec 13.

Abstract

microRNAs (miRNAs or miRs) are endogenous noncoding single‑stranded RNA molecules that can regulate gene expression by targeting the 3'‑untranslated region and play an important role in many biological and pathological processes, such as inflammation and cancer. In this study, we found that miR‑20b was significantly increased in human non‑small cell lung cancer (NSCLC) cell lines and patient tissues, suggesting that it may possess a carcinogenic role in lung cancer. This miRNA promoted the proliferation, migration and invasion of NSCLC cells by targeting and downregulating the expression of adenomatous polyposis coli (APC), which is a negative regulator of the canonical Wnt signaling pathway. Wnt signaling activation may increase transcription of miR‑20b. Therefore, miR‑20b and canonical Wnt signaling were coupled through a feed‑forward positive feedback loop, forming a biological regulatory circuit. Finally, an in vivo investigation further demonstrated that an increase in miR‑20b promoted the growth of cancer cells. Overall, our findings offer evidence that miR‑20b may contribute to the development of NSCLC by inhibiting APC via the canonical Wnt signaling pathway.

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics*
  • Aged
  • Animals
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Feedback, Physiological
  • Female
  • Gene Expression Regulation, Neoplastic
  • Healthy Volunteers
  • Humans
  • Lung / pathology
  • Lung / surgery
  • Lung Neoplasms / blood
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Mice
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Pneumonectomy
  • Wnt Signaling Pathway / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • MIRN20b microRNA, human
  • MicroRNAs