Non-Coding RNA Pvt1 Promotes Cancer Stem Cell-Like Traits in Nasopharyngeal Cancer via Inhibiting miR-1207

Pathol Oncol Res. 2019 Oct;25(4):1411-1422. doi: 10.1007/s12253-018-0453-1. Epub 2018 Aug 23.

Abstract

Nasopharyngeal carcinoma (NPC) is a kind of head-neck malignant tumor. lncRNA-PVT1 can promote the proliferation of carcinoma cells, and induce cells to have stem cell-like potentials. However, the function of PVT1 in NPC cells is not clear. The expressions of lncRNA-PVT1 and the expressions of the stem cell markers in NPC tissues or cell lines were investigated by qRT-PCR or western blot. The cell proliferation, and the ability of NPC cells to form spherical, clonal colonies were investigated by MTT assay, colony formation assay, and tumor-sphere formation assay. Cancer stem cells surface markers were detected by flow cytometry and western blot. PI3K/AKT signal activation in NPC cells was determined by western blot. PVT1 was significantly up-regulated in both NPC tissues and cell lines and associated with poor prognosis. PVT1 knockdown reduced NPC cells viability, clonogenicity, the cell surface CD44+/CD24- stem phenotype, and the expressions of the stem cell markers in NPC cells, including Oct4, c-Myc, SOX2, and ALDH. Furthermore, PVT1 negatively regulates the expression levels of miR-1207 in NPC cells and spheres cells, which is critical for NPC stemness. Knockdown of miR-1207 promoted stem phenotype and the expressions of the stem cell markers in NPC cells. Moreover, phosphor-PI3K (p-PI3K) and phosphor-AKT (p-AKT) were found to be down-regulated after PVT1 siRNAs transfection in NPC cells. And miR-1207 inhibitor transfection reversed the all the effects brought by PVT1 knockdown. Pvt1 promotes cancer stem cell-like properties in NPC cells via inhibiting miR-1207 and activating the PI3K/AKT signal pathway.

Keywords: Nasopharyngeal carcinoma; PI3K/AKT; PVT1; Tumor stem cell; miR-1207.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Phenotype
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • MIRN1207 microRNA, human
  • MicroRNAs
  • PVT1 long-non-coding RNA, human
  • RNA, Long Noncoding