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
Homeobox C8 (HOXC8) is a transcription factor preferentially overexpressed in a large percentage of non-small cell lung carcinoma (NSCLC). To investigate the function of HOXC8 in NSCLC, we showed that knockdown of HOXC8 led to massive NSCLC cell death in a mechanism of pyroptosis because both YVAD, a caspase-1 (CASP1) inhibitor, and disulfiram, which prevents gasdermin D (GSDMD) pore formation, blocked cell death caused by HOXC8 depletion. Intriguingly, ASC, a key component of canonic inflammasome, was dispensable for pyroptosis occurring in HOXC8-depleted cells. Instead, we detected greatly elevated levels of both CASP1 protein and mRNA in HOXC8-knockdown cells. As forced expression of CASP1 is sufficient to induce CASP1 activation and pyroptosis, we reason that pyroptosis led by HOXC8 depletion results from massive increase in the abundance of CASP1. To uncover the functional connection between HOXC8 and CASP1 expression, we revealed that HDAC1/2 was involved in augmented CASP1 transcription induced by HOXC8 knockdown. Moreover, we found that HOXC8 and HDAC1 were in the same immunocomplex and the presence of HOXC8 is required for the recruitment of HDAC1 to CASP1 promoter. Since HOXC8 also binds CASP1 promoter, we conclude that HOXC8 negatively regulates CASP1 expression by drafting HDAC1/2 to CASP1 gene. Finally, we demonstrated that cholesterol-conjugated HOXC8 siRNA was able to slow down NSCLC tumorigenesis. This study suggests that HOXC8 participates NSCLC development by controlling CASP1 expression and pyroptosis.
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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