Enhancer RNA (eRNA) in Human Diseases

Abstract

Enhancer RNAs (eRNAs), a class of non-coding RNAs (ncRNAs) transcribed from enhancer regions, serve as a type of critical regulatory element in gene expression. There is increasing evidence demonstrating that the aberrant expression of eRNAs can be broadly detected in various human diseases. Some studies also revealed the potential clinical utility of eRNAs in these diseases. In this review, we summarized the recent studies regarding the pathological mechanisms of eRNAs as well as their potential utility across human diseases, including cancers, neurodegenerative disorders, cardiovascular diseases and metabolic diseases. It could help us to understand how eRNAs are engaged in the processes of diseases and to obtain better insight of eRNAs in diagnosis, prognosis or therapy. The studies we reviewed here indicate the enormous therapeutic potency of eRNAs across human diseases.

Keywords: cancer; cardiovascular disease; eRNA; enhancer RNA; metabolic disease; neurodegenerative disorder; transcriptional regulation.

Figure 1

The mechanisms of eRNAs transcribed from chr8q24.21. (A) Utilizing CCAT1 as a diagnostic biomarker to distinguish CRC stages (III and IV). (B) The different mechanisms of CCAT1 and CCAT1L in the nucleus and the cytoplasm, as well as the impact on eRNA and follow-up pathways by a variant inside the PVT1 region.

Figure 2

The opposing functions and mechanisms of IRENEs (IRENE-SS and IRENE-div) in regulating Nkx2-5. IRENE-SS, acting as a typical eRNA, enlists NKX2-5 and upregulates Nkx2-5 expression. IRENE-div, on the contrary, recruits SIRT1 to Nkx2-5 enhancer and silences Nkx2-5 expression.

Figure 3

Identified eRNAs in cancer, neurodegenerative disorders, cardiovascular disease and metabolic diseases. In cancers, various eRNAs contribute to carcinogenesis, including CCAT1, MMP9e and other eRNAs mentioned in the figure. CCAT1 and FOXP4-AS1 also show their potential utility in cancer diagnosis, prognosis and therapy. In neurodegenerative disorders, Bdnf-Enh^g1, Bdnf-Enh^g2 and Evf2 are involved in the pathologies of AD, PD and/or HD. The eRNA utNgn1 has shown its possible medical usage. In cardiovascular diseases, CARMEN, RACER and IRENEs have demonstrated their contribution to different cardiac-associated pathways; Wisper, HERNA1, Bvht and Meteor may be applied in future therapies. In metabolic diseases, Lnc-leptin and OLMALINC can regulate gene expressions related to metabolic pathologies. Overexpression of LncASIR, together with inducing its binding protein, may be applied in T2D treatment.