Nuclear Receptor Subfamily 5 Group A Member 2

Nuclear Receptor Subfamily 5 Group A Member 2 (NR5A2, LRH-1) is an oncogene in a wide range of cancer types. Bioinformatics analysis on glioblastoma multiforme (GBM) tumors has revealed that the miR-139-5p-NR5A2 axis may be putatively regulated by the long non-coding RNA (lncRNA) RP3-439F8.1. This led Qi et al. to hypothesize the existence of a RP3-439F8.1-miR-139-5p-NR5A2 regulatory axis in GBM cells.

Gene expression analysis was performed in GBM tumor samples and normal controls from the hospital, The Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM) cohort, and the Gene Expression Omnibus (GEO) database (GSE7696). Cell proliferation, apoptosis, Matrigel Transwell, colony formation, and cell cycle assays were performed in T98 G and U251 cells in vitro. An orthotopic U251 xenograft murine model was employed to test the effects of RP3-439F8.1 knockdown in vivo.

NR5A2 was upregulated in the three independent GBM tumor cohorts. In vitro, NR5A2 overexpression enhanced GBM cell proliferation, colony formation, invasiveness, and G0-G1 cell cycle phase shift via co-activating β-catenin/TCF4 signaling, with no apparent effect upon apoptosis. In contrast, RP3-439F8.1 knockdown produced the opposite effects. RP3-439F8.1 knockdown reduced tumor progression in vivo, increasing overall survival in model mice. Further in vitro experiments revealed that RP3-439F8.1 acts as a competing endogenous RNA (ceRNA) to regulate NR5A2 by sponging the microRNA miR-139-5p. These findings were clinically validated by a positive correlation between RP3-439F8.1 and NR5A2 and a negative correlation between RP3-439F8.1 and miR-139-5p in GBM tumors.

The study supports a tumorigenic role for RP3-439F8.1 in GBM through the RP3-439F8.1/miR-139-5p/NR5A2 axis 1)

Qi J, Pan L, Yu Z, Ni W. The lncRNA RP3-439F8.1 promotes GBM cell proliferation and progression by sponging miR-139-5p to upregulate NR5A2. Pathol Res Pract. 2021 Jan 2;223:153319. doi: 10.1016/j.prp.2020.153319. Epub ahead of print. PMID: 33991848.
  • mir-139-5p.txt
  • Last modified: 2021/05/17 10:33
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