인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
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
Radiotherapy (RT) is a crucial treatment for hepatocellular carcinoma (HCC); however, resistance to radiation remains a major challenge to its effectiveness. Circular RNAs (circRNAs), traditionally considered stable non-coding RNAs, have recently gained attention for their potential to encode proteins or peptides that play crucial roles in HCC radioresistance. In this study, circSNX25 (has_circ_0004874) was identified as a novel circRNA with coding potential related to radiation resistance in HCC through circRNA sequencing, Northern blotting, and mass spectrometry (MS). We demonstrated that SNX25-215, a novel protein encoded by circSNX25, rather than the parental circSNX25 itself, promotes resistance to radiotherapy in HCC cells both in vitro and in vivo. Co-immunoprecipitation (co-IP) and molecular docking revealed that amino acids H207 and E214 of SNX25-215 are critical for binding to Golgi to ER traffic protein 4 homolog (GET4). This interaction inhibits the binding of BCL2-associated athanogene 6 (BAG6) to GET4, thereby exposing the nuclear localization sequence (NLS) of BAG6 and facilitating its nuclear translocation. This, in turn, enhances DNA damage repair, ultimately increasing resistance to ionizing radiation (IR) in HCC cells. Importantly, elevated levels of SNX25-215 lead to nuclear localization of BAG6, endowing HCC cells with radioresistant activity, which is further supported by clinical evidence. Our findings highlight the potential of circSNX25 as a prognostic biomarker and a therapeutic target for overcoming radioresistance in HCC. This study provides deeper insights into the roles that circRNA-encoded proteins play in HCC radioresistance.
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.