인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
크롬 서지관리 다운로드
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
The modification of histone H3, particularly at the 27th lysine residue, plays a pivotal role in regulating gene expression. Methylation or acetylation of H3K27 significantly impacts the compaction of DNA around histones, thereby affecting gene accessibility to transcriptional machinery. Dysregulation or mutation of enzymes modulating H3K27 in pediatric cancer implies a link between these modifications and cancer development. Understanding these modifications on gene expression could lead to targeted therapies or specific diagnostic tools for pediatric tumors. Our project investigated tumor growth trends in high-grade gliomas, which constitute 20% of aggressive pediatric brain tumors. This project studied the effect of p53 and PDGFRA genes on tumorigenesis and proliferation regulation in the brain. p53, a tumor suppressor, is the most frequently altered gene in tumors, and missense mutations of p53 boost cancer cell proliferation and survival. Conversely, PDGFRA overexpression enhances tumor growth. Our hypothesis suggested that p53 knockout alongside PDGFRA activation would promote tumor growth. Hence, we designed the LCL mouse model with PDGFRA overexpression and p53 knockout to examine tumor progression. Another project focus was the Smad nuclear-interacting protein 1 (SNIP1) which is involved in gene regulation and transcriptional control. SNIP1 interacts with the Polycomb repressive complex 2 (PRC2), which methylates histone H3 at lysine 27 (H3K27me3). Therefore, SNIP1 involvement with PRC2 modulates chromatin structure via histone modifications, potentially impacting cell cycle regulation genes and influencing cancer development. To assess SNIP1's role in altering tumor development, we designed the TBH mouse model with PDGFRA overexpression, p53 knockout, and SNIP1 knockout. Cre activity to knock out p53 and SNIP1 in mice was induced through intraperitoneal injection of 3 mg tamoxifen solution per kg of body weight at postnatal days 0 and 1, with a 24-hour interval between injections. Following this, mice were monitored for symptoms like weight loss and motor impairments. Subsequently, mouse brains were harvested, fixed in PFA, and cryosectioned. Immunofluorescence staining was conducted with specific antibodies Ki67 (a cell proliferation marker), Olig 2 (a glioma marker), PH3 (a marker for phosphorylated histone H3), and Neun (a neuronal marker). We detected immunofluorescence signals for Ki67, Olig 2, and PH3 in LCL and TBH mouse lines confirming that p53 loss and PDGFRA activation are modifications of H3K27 that promote pediatric glioma development. Neun was undetected in both lines, confirming neuronal cell replacement by tumor cells. The uniform immunofluorescent signals for Ki67, Olig 2, and PH3 in LCL and TBH lines indicated that SNIP1 knockout has no significant effect on tumor growth. Furthermore, the uniform survival curve for both lines affirmed that SNIP1 had no significant effect on the tumor development timeframe. This study contributes significantly to understanding the molecular mechanisms underlying pediatric glioma development and identifies potential therapeutic targets for future biomedical advancements aimed at gliomas. We thank Sharon King, DNB imaging core, the ARC animal facility staff, and Alfonso Lavado in the histology core at St. Jude Children's Research Hospital. We thank Eric Rivera-Peraza and Logan Rayburn for experimental assistance. This work is funded by St. Jude Children's Research Hospital and the American Lebanese Syrian Associated Charities.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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