Oncogenic seRNA functional activation: a novel mechanism of tumorigenesis

Abstract

seRNA is a noncoding RNA (ncRNA) transcribed from active super-enhancer (SE), through which SE exerts biological functions and participates in various physiological and pathological processes. seRNA recruits cofactor, RNA polymerase II and mediator to constitute and stabilize chromatin loop SE and promoter region, which regulates target genes transcription. In tumorigenesis, DNA insertion, deletion, translocation, focal amplification and carcinogen factor mediate oncogenic SE generation, meanwhile, oncogenic SE transcribes into tumor-related seRNA, termed as oncogenic seRNA. Oncogenic seRNA participates in tumorigenesis through activating various signal-pathways. The recent reports showed that oncogenic seRNA implicates in a widespread range of cytopathological processes in cancer progression including cell proliferation, apoptosis, autophagy, epithelial-mesenchymal transition, extracellular matrix stiffness and angiogenesis. In this article, we comprehensively summarized seRNA's characteristics and functions, and emphatically introduced inducible formation of oncogenic seRNA and its functional mechanisms. Lastly, some research strategies on oncogenic seRNA were introduced, and the perspectives on cancer therapy that targets oncogenic seRNA were also discussed.

Disruption of super-enhancer-driven tumor suppressor gene RCAN1.4 expression promotes the malignancy of breast carcinoma

“…SEs have been identified as a unique type of transcriptional regulation involved in cancer development [ 33 , 34 ]. Specifically, this epigenomic signature is often established to activate oncogenes through a variety of mechanisms, including DNA insertion, deletion, translocation, focal amplification, overexpression of an oncogenic transcription factor, and so on [ 26 , 35 , 36 ]. However, the role and the mechanisms by which super enhancers regulate the expression of tumour suppressor genes are not well understood.…”

The mechanism and function of super enhancer RNA

“…Disorder in SEs might be a reason for aberrant transcription of oncogenes. Single nucleotide polymorphisms (SNP), DNA translocation, TF overexpression and focal amplification contribute to the change observed in SEs (Tan, Li, & Tang, 2020).…”

“…SeRNA is also involved in the progression of nearly all tumors, including their formation, proliferation, apoptosis, migration, adhesion, and immune response (Tan et al, 2020). The cancer-associated seRNAs, like HCCL5 (Peng et al, 2019) and LINC01503 (Xie et al, 2018), play a critical role in various aspects of tumor occurrence and progression.…”

Super-Enhancers in the Regulation of Gene Transcription: General Aspects and Antitumor Targets

“…Super-enhancers express eRNA at a higher level than conventional enhancers do; in addition, eRNAs are more often expressed from the super-enhancers rather than from conventional enhancers [ 10 ]. eRNAs can be involved in the activation of the expression of the corresponding gene but can also activate other genes, including those located on other chromosomes, thus spreading the impact of the enhancer (distant regulation of the genome) [ 16 ].…”

“…Certain eRNAs associated with “oncogenic” super-enhancers have oncogenic properties themselves. These eRNAs are involved in the regulation of the key processes: proliferation, apoptosis, autophagy, epithelial–esenchymal transition, and angiogenesis [ 16 ].…”