Zhigang Huang, Bin Liu, Xiaoju Li, Chenghua Jin, Quansen Hu, Zhiwei Zhao, Qian Wang
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引用次数: 0
Abstract
Long noncoding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) show high expression in various cancers with elusive regulatory mechanisms. This study investigated the regulatory mechanism of FOXD2-AS1 in clear cell renal cell carcinoma (ccRCC) and its influence on ccRCC cell functions, providing novel insights into ccRCC treatment and a theoretical basis for refining prognoses of ccRCC patients.
Through differential analysis and survival analysis, differentially expressed lncRNAs (DElncRNAs) that were significantly linked with the prognosis of ccRCC were initially identified, and lncRNA-transcription factor-mRNA triplet was predicted via lncMAP database. RNA immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays were applied to verify the targeted relationship between MYC, FOXD2-AS1, and Egl-9 family hypoxia-inducible factor 3 (EGLN3). Cell functions in ccRCC were detected by a set of cell functional assays. Mice experiment was utilized for in vivo validation.
We uncovered the elevated FOXD2-AS1 and EGLN3 expression in ccRCC, as well as the promotion effect of FOXD2-AS1 on ccRCC cells to proliferate, migrate, and invade via upregulating EGLN3 expression. Our results also suggested that the regulatory influence of FOXD2-AS1 on EGLN3 was achieved by recruiting MYC to the EGLN3 promoter region. In vitro and in vivo assays both confirmed that the FOXD2-AS1/MYC/EGLN3 axis could accelerate the progression of ccRCC.
FOXD2-AS1 activated EGLN3 to accelerate ccRCC cell functions via binding to the transcription factor MYC.
期刊介绍：
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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