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Published on: May 14, 2016
Aberrant GIMAP2 expression affects oral squamous cell carcinoma progression by promoting cell cycle and inhibiting
Mari Komatsu1, Kengo Saito2, Isao Miyamoto3
1Department of Oral Science, Chiba University, Chiba 260-8670, Japan.
Abstract:
GTPases of immunity-associated protein 2 (GIMAP2) is a GTPase family member associated with T cell survival. However, its mechanisms of action in oral squamous cell carcinoma (OSCC) remain largely unknown. Therefore, the present study aimed to elucidate the possible role of GIMAP2 in OSCC development by investigating its expression levels and molecular mechanisms in OSCC. Reverse transcription quantitative PCR, immunoblotting and immunohistochemistry indicated that GIMAP2 expression was significantly upregulated (P<0.05) in OSCC-derived cell lines and primary OSCC specimens compared with that in their normal counterparts. GIMAP2-knockdown OSCC cells exhibited decreased cell growth, which was associated with cyclin-dependent kinase (CDK)4, CDK6 and phosphorylated Rb downregulation and p53 and p21 upregulation. In addition to cell cycle arrest, GIMAP2 affected anti-apoptotic functions in GIMAP2-knockdown cells by upregulating Bcl-2 and downregulating Bax and Bak. These findings indicated that GIMAP2 may significantly influence OSCC development and apoptosis inhibition and thus is a potential biomarker of OSCC.
Insights
GTPases of immunity-associated protein 2 (GIMAP2) is upregulated in oral squamous cell carcinoma (OSCC). GIMAP2 knockdown inhibits OSCC cell growth and promotes apoptosis, suggesting it is a potential OSCC biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- GTPases of immunity-associated protein 2 (GIMAP2) is linked to T cell survival.
- The role of GIMAP2 in oral squamous cell carcinoma (OSCC) is not well understood.
Purpose of the Study:
- To investigate the expression and molecular mechanisms of GIMAP2 in OSCC.
- To determine if GIMAP2 plays a role in OSCC development and apoptosis.
Main Methods:
- Reverse transcription quantitative PCR (RT-qPCR) to assess GIMAP2 mRNA levels.
- Immunoblotting and immunohistochemistry to evaluate GIMAP2 protein expression.
- GIMAP2 knockdown experiments in OSCC cell lines.
Main Results:
- GIMAP2 expression was significantly upregulated in OSCC cell lines and tissues compared to normal controls.
- GIMAP2 knockdown led to decreased cell growth, cell cycle arrest (downregulation of CDK4, CDK6, p-Rb; upregulation of p53, p21).
- GIMAP2 knockdown affected anti-apoptotic functions by upregulating Bcl-2 and downregulating Bax and Bak.
Conclusions:
- GIMAP2 significantly influences OSCC development by promoting cell proliferation and inhibiting apoptosis.
- GIMAP2 is a potential diagnostic biomarker for oral squamous cell carcinoma.
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