PWRN1 Suppressed Cancer Cell Proliferation and Migration in Glioblastoma by Inversely Regulating hsa-miR-21-5p

Cancer Manag Res. 2020 Jul 2:12:5313-5322. doi: 10.2147/CMAR.S250166. eCollection 2020.

Abstract

Objective: To evaluate the expression and function of long noncoding RNA (lncRNA) Prader-Willi region non-protein coding RNA 1 (PWRN1) in human glioblastoma (GBM).

Materials and methods: QRT-PCR was applied to assess PWRN1 expression in human GBM tumors and GBM cell lines. PWRN1 was overexpressed by lentiviral infection in LN-229 and U-251 cells to evaluate its effect on GBM cell proliferation and migration in vitro, and xenograft in vivo. The endogenously competing target of PWRN1, human microRNA-21-5p (hsa-miR-21-5p) was evaluated by dual-luciferase activity assay and qRT-PCR. Also, hsa-miR-21-5p was upregulated in PWRN1-overexpressed GBM cells to evaluate the functional involvement of hsa-miR-21-5p in PWRN1-mediated GBM cell proliferation and migration.

Results: PWRN1 was downregulated in both human GBM tumors and GBM cell lines. In LN-229 and U-251, PWRN1 overexpression suppressed cancer cell proliferation and migration in vitro, and xenograft growth in vivo. Hsa-miR-21-5p was demonstrated to be the downstream competing target of PWRN1 in GBM. Conversely, upregulating hsa-miR-21-5p in LN-229 and U-251 cells reversed the tumor-suppressing effects of PWRN1 overexpression.

Conclusion: PWRN1 is markedly downregulated in GBM. Overexpressing PWRN1 has tumor inhibitory effect on GBM cells, likely via reversely suppressing the expression of tumor oncogenic factor of hsa-miR-21-5p.

Keywords: GBM; PWRN1; hsa-miR-21-5p; lncRNAs; microRNA; migration.