J Cancer 2020; 11(6):1359-1370. doi:10.7150/jca.36083
The RNA-binding protein QKI suppresses tumorigenesis of clear cell renal cell carcinoma by regulating the expression of HIF-1α
1. Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an710032, China
2. Department of Urology, The 201 Military Hospital, Liaoyang 111000, China
3. State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an710032, China.
4. School of Medicine, St. George's University, Grenada.
*These authors contributed equally to this work.
Shi F, Wei D, Zhu Z, Yan F, Wang F, Zhang K, Li X, Zheng Y, Yuan J, Lu Z, Yuan J. The RNA-binding protein QKI suppresses tumorigenesis of clear cell renal cell carcinoma by regulating the expression of HIF-1α. J Cancer 2020; 11(6):1359-1370. doi:10.7150/jca.36083. Available from https://www.jcancer.org/v11p1359.htm
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.
Keywords: QKI, tumor suppressor, HIF-1α, survival, biomarker background