LncRNA DGCR5 contributes to CSC-like properties via modulating miR-330-5p/CD44 in NSCLC

J Cell Physiol. 2018 Sep;233(9):7447-7456. doi: 10.1002/jcp.26590. Epub 2018 Apr 16.

Abstract

Non-coding RNAs can exert significant roles various cancers, including NSCLC. Previously, we indicated that lncRNA DGCR5 can promote lung cancer progression through inhibiting hsa-mir-22-3p. In our current study, we investigated the role of DGCR5 in cancer stem cell-like properties of NSCLC. CSCs have been recognized as the frequent cause of tumor metastasis, tumor recurrence, and chemotherapy resistance. Here, lung cancer stem cells were successfully enriched from the parental NSCLC A549, H460, and H1299 cells by using tumor sphere formation assays and side population (SP) assays. We observed that DGCR5 was up-regulated in the enriched CSCs of NSCLC. DGCR5 can inhibit the stemness of NSLCL while overexpression of DGCR5 promoted CSC-like traits. In addition, miR-330-5p was predicted as target of DGCR5 and the correlation between them was validated by dual-luciferase reporter assay, RIP assay, and RNA pull-down assay. Meanwhile, it was found that miR-330-5p was decreased in CSCs of NSCLC. miR-330-5p mimics repressed the stemness while miR-330-5p inhibition enhanced CSC-like properties by targeting CD44. Taken these together, DGCR5 can act as a crucial regulator of CSCs in NSCLC by modulating miR-330-5p/CD44 axis.

Keywords: CD44; CSCs; DGCR5; NSCLC; miR-330-5p.

MeSH terms

  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • CD44 protein, human
  • Hyaluronan Receptors
  • MIRN330 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • long noncoding RNA DGCR5, human