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Positive feedback regulation of lncRNA PVT1 and HIF2α contributes to clear cell renal cell carcinoma tumorigenesis and metastasis
- Source :
- Oncogene
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Long noncoding RNAs (lncRNAs) have been reported to exert important roles in tumors, including clear cell renal cell carcinoma (ccRCC). PVT1 is an important oncogenic lncRNA which has critical effects on onset and development of various cancers, however, the underlying mechanism of PVT1 functioning in ccRCC remains largely unknown. VHL deficiency-induced HIF2α accumulation is one of the major factors for ccRCC. Here, we identified the potential molecular mechanism of PVT1 in promoting ccRCC development by stabilizing HIF2α. PVT1 was significantly upregulated in ccRCC tissues and high PVT1 expression was associated with poor prognosis of ccRCC patients. Both gain-of-function and loss-of function experiments revealed that PVT1 enhanced ccRCC cells proliferation, migration, and invasion and induced tumor angiogenesis in vitro and in vivo. Mechanistically, PVT1 interacted with HIF2α protein and enhanced its stability by protecting it from ubiquitination-dependent degradation, thereby exerting its biological significance. Meanwhile, HIF2α bound to the enhancer of PVT1 to transactivate its expression. Furthermore, HIF2α specific inhibitor could repress PVT1 expression and its oncogenic functions. Therefore, our study demonstrates that the PVT1/ HIF2α positive feedback loop involves in tumorigenesis and progression of ccRCC, which may be exploited for anticancer therapy.
- Subjects :
- 0301 basic medicine
Cancer Research
Carcinogenesis
Biology
medicine.disease_cause
Article
Metastasis
Prognostic markers
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Genetics
medicine
Humans
Enhancer
Carcinoma, Renal Cell
Molecular Biology
Mechanism (biology)
Ubiquitination
medicine.disease
Renal cell carcinoma
Kidney Neoplasms
Up-Regulation
PVT1
Clear cell renal cell carcinoma
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
RNA, Long Noncoding
Function (biology)
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....cd77e9acfb1cbb3e59f28806bff84fa8