FOXD2‐AS1 Binding to MYC Activates EGLN3 to Affect the Malignant Progression of Clear Cell Renal Cell Carcinoma

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.