| Literature DB >> 28257806 |
Weijun Liu1, Hanxiang Chen2, Nathan Wong1, Wesley Haynes1, Callie M Baker1, Xiaowei Wang3.
Abstract
Pseudohypoxia plays a central role in the progression and therapeutic resistance of clear cell renal cell carcinoma (ccRCC); however, the underlying mechanisms are poorly understood. MicroRNA miR-126 has decreased expression in metastatic or relapsed ccRCC as compared to primary tumors, but the mechanisms by which miR-126 is implicated in RCC remain unknown. Through RNA-seq profiling to evaluate the impact of overexpression or CRISPR knockout of miR-126, we have identified SERPINE1 as a miR-126-5p target regulating cell motility, and SLC7A5 as a miR-126-3p target regulating the mTOR/HIF pathway. Specifically, miR-126 inhibits HIFα protein expression independent of von Hippel-Lindau tumor suppressor (VHL). On the other hand, deactivation of miR-126 induces a pseudohypoxia state due to increased HIFα expression, which further enhances therapeutic resistance and cell motility mediated by SLC7A5 and SERPINE1, respectively. Finally, the clinical relevance of miR-126 modulated gene regulation in ccRCC has been confirmed with profiling data from The Cancer Genome Atlas.Entities:
Keywords: Hypoxia; MicroRNA; Pseudohypoxia; Renal cell carcinoma; miR-126
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Year: 2017 PMID： 28257806 PMCID： PMC5389460 DOI： 10.1016/j.canlet.2017.02.025
Source DB: PubMed Journal: Cancer Lett ISSN： 0304-3835 Impact factor: 8.679