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 RON receptor tyrosine kinase is critical in the pathogenesis of various cancer types, however, its role in bladder cancer invasive growth is still largely unknown. Here, we found that over 90% of bladder cancer samples exhibit elevated levels of RON expression, with significantly higher expression levels observed in invasive bladder cancer compared to non-invasive bladder cancer. In vitro, RON activation resulted in increased bladder cancer cell migration and invasiveness. Results from mRNA sequencing and transcriptome analysis further demonstrated that MMP12, a downstream molecule of RON, is functionally involved in regulating RON-mediated bladder cancer cell migration and invasiveness. The underlying mechanism appeared to be the RON-mediated inhibition of HIF-2α ubiquitination, which is channeled through the activation of the JNK signaling pathway. Consequently, the activated JNK pathway increased MMP12 expression, ultimately driving bladder cancer cell migration and invasion. As evident in bioinformatics and dual-luciferase reporter assays, the RON mRNA at its 3'-untranslated regions specifically interacted with hsa-miR-659-3p. The binding of hsa-miR-659-3p downregulated the RON gene expression, attenuating the receptor-mediated tumorigenic activities of bladder cancer cells in vitro and in vivo. In conclusion, aberrant RON expression in bladder cancer cells and MMP12 and HIF-2α activities form a functional axis that causes increased bladder cancer cell migration and invasion. The fact that hsa-miR-659-3p downregulates RON expression indicates its critical role in attenuating RON-mediated tumorigenic effect on bladder cancer cells. These findings highlight the importance of RON targeting as a therapeutic means for potential bladder cancer therapy.
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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