MiR-127-3p inhibits cell growth and invasiveness by targeting ITGA6 in human osteosarcoma

IUBMB Life. 2018 May;70(5):411-419. doi: 10.1002/iub.1710. Epub 2018 Mar 23.

Abstract

Osteosarcoma (OS) is one of the most universal malignant bone tumors that occur mostly in children and adolescents. This study aimed to investigate the roles of miR-127-3p and integrin subunit-α 6 (ITGA6) in OS proliferation, apoptosis, invasion and migration, and to explore the possible molecular mechanism and target relationship. By conducting quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, the microRNA (miRNA) and protein expressions of miR-127-3p and ITGA6 in both tissues and cells were determined. The expression of apoptosis and migration related were also detected by western blot. The target relationship between miR-127-3p and ITGA6 was predicted by TargetScan and verified by dual-luciferase reporter assay. The biological functions of miR-127-3p and ITGA6 in OS were investigated by following experiments: cell counting kit 8 (CCK-8) and colony formation assays to inspect cell proliferation, flow cytometry, and caspase 3 activity assay to examine apoptosis, and transwell and wound healing assays to analyze invasion and migration. Significant down-regulation of miR-127-3p and up-regulation of ITGA6 was found out in OS tissues and cells. ITGA6 was proved to be the downstream target gene of miR-127-3p and functioned as a tumor promotor in OS, while miR-127-3p restrained deterioration of OS by suppressing cell viability, reducing migration and invasion, and promoting apoptosis. MiR-127-3p suppressed proliferation, invasion, and migration while stimulated apoptosis of OS cells through knocking down ITGA6. © 2018 IUBMB Life, 70(5):411-419, 2018.

Keywords: ITGA6; miR-127-3p; osteosarcoma.

MeSH terms

  • 3' Untranslated Regions
  • Base Sequence
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Integrin alpha6 / genetics*
  • Integrin alpha6 / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • Osteoblasts / metabolism*
  • Osteoblasts / pathology
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Signal Transduction
  • Transcription, Genetic

Substances

  • 3' Untranslated Regions
  • ITGA6 protein, human
  • Integrin alpha6
  • MIRN127 microRNA, human
  • MicroRNAs
  • CASP3 protein, human
  • Caspase 3