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Expression and functional characterization of LRRC4, a novel brain-specific member of the LRR superfamily
Qiuhong Zhang1, Jieru Wang, Songqing Fan
1Cancer Research Institute, Central South University, Changsha 410078, Hunan, People's Republic of China.
Abstract:
LRRC4, a novel member of LRR superfamily thought to be involved in development and tumorigenesis of the nervous tissue, has the potential to suppress tumorigenesis and cell proliferation of U251MG cells. This study aimed at revealing the correlation between expression of LRRC4 and the maintenance of normal function and tumorigenesis suppression within the central nervous system. We systematically analyzed the expression and tissue distributions of the gene in tissues. Results showed that LRRC4 expression was limited to normal adult brain, both in human and in mouse, and exhibited a development-regulated pattern, but was down-regulated in brain tumor tissues and U251MG cell line. Furthermore, dynamic alterations in gene expression associated with cell cycle progression were investigated by using Tet-on system. Results showed that LRRC4 induced a cell cycle delay at the late G1 phase, probably through the alteration of the expression of different cell cycle regulating proteins responsible for mediating G1-S progression, such as p21(Waf1/Cip1) and p27(Kip1), Cdk2 and PCNA, p-ERK1/2. These findings suggest that LRRC4 may play an important role in maintaining normal function and suppressing tumorigenesis in the central nervous system.
Insights
Leucine-rich repeat-containing protein 4 (LRRC4) suppresses brain tumor growth by regulating cell cycle progression. Its down-regulation in brain tumors suggests a role in central nervous system tumor suppression.
Area of Science:
- Neuroscience
- Molecular Biology
- Oncology
Background:
- LRRC4, a member of the LRR superfamily, is implicated in nervous system development and tumorigenesis.
- LRRC4 exhibits potential for suppressing tumorigenesis and cell proliferation.
Purpose of the Study:
- To investigate the correlation between LRRC4 expression and the maintenance of normal central nervous system (CNS) function.
- To determine the role of LRRC4 in CNS tumor suppression.
Main Methods:
- Systematic analysis of LRRC4 gene expression and tissue distribution in human and mouse tissues.
- Utilizing the Tet-on system to study dynamic alterations in gene expression during cell cycle progression.
- Assessing the impact of LRRC4 on cell cycle regulators like p21(Waf1/Cip1), p27(Kip1), Cdk2, PCNA, and p-ERK1/2.
Main Results:
- LRRC4 expression is restricted to the normal adult brain in both humans and mice, showing a development-regulated pattern.
- LRRC4 expression is significantly down-regulated in brain tumor tissues and the U251MG cell line.
- LRRC4 induces a delay in the late G1 phase of the cell cycle, affecting G1-S progression regulators.
Conclusions:
- LRRC4 plays a crucial role in maintaining normal CNS function.
- LRRC4 acts as a tumor suppressor in the central nervous system, likely by modulating cell cycle progression.
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