miR-4326 promotes lung cancer cell proliferation through targeting tumor suppressor APC2

Mol Cell Biochem. 2018 Jun;443(1-2):151-157. doi: 10.1007/s11010-017-3219-2. Epub 2017 Nov 3.

Abstract

microRNAs have been reported to play vital role in lung cancer proliferation and metastasis; the role of miR-4326 in tumor progression has not been studied. Here, we studied the effect of miR-4326 on lung cancer cell proliferation; we found that miR-4326 was significantly upregulated in lung cancer tissues determined using TCGA dataset and clinical specimens, meanwhile it was also upregulated in lung cancer cells. Overexpression of miR-4326 promoted lung cancer cell proliferation analyzed by MTT, soft agar growth, and BrdU incorporation assay, while miR-4326 knockdown suppressed lung cancer cell proliferation. We found miR-4326 targets tumor suppressor adenomatous polyposis coli 2 (APC2), which is a negative regulator of Wnt pathway, by binding to the 3'UTR of APC2. Wnt pathway could increase Cyclin D1 and c-MYC expression, we also found that miR-4326 could increase their expression, suggesting that APC2 was the target of miR-4326. Moreover, double knockdown of APC2 and miR-4326 promoted lung cancer cell proliferation, confirming that miR-4326 promoted lung cancer cell proliferation by inhibiting APC2.

Keywords: APC2; Lung cancer; Proliferation; miR-4326.

MeSH terms

  • 3' Untranslated Regions
  • A549 Cells
  • Cell Proliferation*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Wnt Signaling Pathway*

Substances

  • 3' Untranslated Regions
  • APC2 protein, human
  • Cytoskeletal Proteins
  • MicroRNAs
  • RNA, Neoplasm
  • Tumor Suppressor Proteins