Research Paper Volume 12, Issue 24 pp 25865—25877

Downregulation of enhancer RNA EMX2OS is associated with poor prognosis in kidney renal clear cell carcinoma

Huiming Jiang1, *, , Haibin Chen2, *, , Pei Wan1, , Shengda Song1, , Nanhui Chen1, ,

  • 1 Department of Urology, Meizhou People’s Hospital, Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou 514031, Guangdong Province, P.R. China
  • 2 Department of Histology and Embryology, Shantou University Medical College, Shantou 515041, Guangdong Province, P.R. China
* Equal contribution

Received: June 19, 2020       Accepted: September 29, 2020       Published: November 25, 2020
How to Cite

Copyright: © 2020 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Enhancer RNAs are a subclass of long non-coding RNAs transcribed from enhancer regions that play an important role in the transcriptional regulation of genes. However, their role in kidney renal clear cell carcinoma (KIRC) is largely unknown. Herein, we identified the key enhancer RNAs in KIRC via an integrated data analysis method. Gene expression profiles and clinical data of KIRC and 32 other cancer types were acquired using the University of California Santa Cruz Xena platform. Reported enhancer RNAs and genes regulated by them were selected as putative enhancer RNA-target pairs. Kaplan-Meier survival and correlation analyses were performed to identify the key enhancer RNAs. Finally, EMX2OS was identified as the enhancer RNA most associated with survival, with EMX2 as its target. EMX2OS downregulation was significantly associated with higher histological grade, advanced stage, and poorer prognosis. The results were validated in pan-cancer data from The Cancer Genome Atlas and RT-qPCR analysis of 12 pairs of KIRC and normal real-world samples. Functional enrichment analysis indicated that several metabolism-associated signaling pathways were enriched. This study demonstrated that EMX2OS is a key metabolism-associated enhancer RNA in KIRC with a favorable impact on survival and may be a novel therapeutic target in KIRC.


KIRC: kidney renal clear cell carcinoma; eRNA: enhancer RNA; OS: overall survival; TCGA: The Cancer Genome Atlas; PresSTIGE: Predicting Specific Tissue Interactions of Genes and Enhancers; RT-qPCR: quantitative reverse transcription polymerase chain reaction; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; AJCC: American Joint Committee on Cancer.