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The tumor suppressor NOR1 suppresses cell growth, invasiveness, and tumorigenicity in glioma
1Hunan Provincial Cancer Hospital and Cancer Hospital Affiliated to Xiangya Medical School, Central South University, Changsha, China.
Abstract:
Oxidored-nitro domain-containing protein 1 (NOR1) is a tumor suppressor downregulated in various human cancers, including nasopharyngeal carcinoma (NPC), lung cancer, and testicular cancer. NOR1 protein is highly expressed in the normal brain; however, its role in brain tumors remains unknown. In this study, we demonstrated that the NOR1 protein level was decreased in glioma tissue samples as compared to its normal counterpart. Exogenously expressed NOR1 protein in glioma U251 cells inhibits tumor cell proliferation, migration, and invasion. Re-expression of NOR1 induced cell cycle S to G2 phase arrest and suppressed its tumorigenicity in nude mice. Overexpression of NOR1 in U251 cells also led to a decrease of Ki67 expression in xenografts. Transcriptomic analysis revealed that NOR1 expression altered the expression of genes favored cell proliferation. Among the differentially expressed genes, FOXR2, a member of the FOX gene family, which promotes glioma progression, was decreased in NOR1 expressing cells. The downregulation of FOXR2 by NOR1 was validated in vitro and in vivo. Our findings suggest for the first time that NOR1 suppresses glioma progression via modulating the FOXR2 expression.
Insights
Oxidored-nitro domain-containing protein 1 (NOR1) is downregulated in glioma. NOR1 re-expression inhibits glioma progression by reducing cell proliferation and downregulating FOXR2, a key glioma-promoting gene.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Oxidored-nitro domain-containing protein 1 (NOR1) functions as a tumor suppressor in various cancers.
- NOR1 is highly expressed in the normal brain, but its role in glioma is unexplored.
Purpose of the Study:
- To investigate the role of NOR1 in glioma.
- To determine the molecular mechanisms by which NOR1 affects glioma progression.
Main Methods:
- NOR1 protein levels were assessed in glioma tissues and cell lines.
- NOR1 was exogenously expressed in U251 glioma cells.
- Cell proliferation, migration, invasion, and cell cycle were analyzed.
- Tumorigenicity was evaluated in nude mice xenografts.
- Transcriptomic analysis was performed to identify NOR1-regulated genes.
- FOXR2 expression was validated in vitro and in vivo.
Main Results:
- NOR1 protein levels were decreased in glioma tissues compared to normal brain.
- Exogenous NOR1 expression inhibited glioma cell proliferation, migration, and invasion.
- NOR1 re-expression induced S to G2 cell cycle arrest and suppressed tumor growth in vivo.
- NOR1 overexpression decreased Ki67 expression in xenografts.
- Transcriptomic analysis revealed NOR1 altered genes promoting proliferation, including downregulation of FOXR2.
- NOR1-mediated downregulation of FOXR2 was confirmed.
Conclusions:
- NOR1 acts as a tumor suppressor in glioma.
- NOR1 suppresses glioma progression by inhibiting cell proliferation and invasion.
- NOR1 modulates glioma progression, at least partly, through the downregulation of FOXR2.
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