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The RNA-binding protein QKI suppresses tumorigenesis of clear cell renal cell carcinoma by regulating the expression of HIF-1α

Backgrounds: A number of genetic and biological phenomena imply that tumorigenesis of clear cell renal cell carcinoma (ccRCC) is highly correlated with hypoxia-induced factor-1a (HIF-1α). Recently, research focusing on the post-transcriptional regulation of HIF-1α has provided a new perspective for...

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Detalles Bibliográficos
Autores principales: Shi, Fei, Wei, Di, Zhu, Zheng, Yan, Fei, Wang, Fuli, Zhang, Keke, Li, Xi'an, Zheng, Yu, Yuan, Jiarui, Lu, Zifan, Yuan, Jianlin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995368/
https://www.ncbi.nlm.nih.gov/pubmed/32047543
http://dx.doi.org/10.7150/jca.36083
Descripción
Sumario:Backgrounds: A number of genetic and biological phenomena imply that tumorigenesis of clear cell renal cell carcinoma (ccRCC) is highly correlated with hypoxia-induced factor-1a (HIF-1α). Recently, research focusing on the post-transcriptional regulation of HIF-1α has provided a new perspective for ccRCC therapy. In this study, we observed the expression pattern of the RNA-binding protein QKI, which could regulate HIF expression in ccRCC both in vitro and in vivo. Methods: Tissue microarraywas subjected to immunohistochemistry and tumour cell lines and nude mice were used for in vitro and in vivo assays. QKI overexpression or knockdown was assessed in renal cancer cells. Results: The overexpression of QKI inhibited the proliferation of the 786-0 and caki-1 cells, blocked the cells' entry into the S phase, and promoted apoptosis. In ectopic-implantation nude mice model, QKI depletion significantly increased tumor sizes and initiation rates. Tissue microarrays showed that the expression of QKI genes, and especially QKI-6, was significantly decreased in tumor tissues compared with these in normal kidney tissues. Moreover, decreased QKI expression was closely correlated with high tumor grade, poor differentiation, and poor survival. Conclusions: QKI may be useful as a novel, independent diagnostic and biological marker for ccRCC.