Emerging role of long noncoding RNA-encoded micropeptides in cancer
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Cancer Cell International Open Access
REVIEW
Emerging role of long noncoding RNAencoded micropeptides in cancer Mujie Ye1,2† , Jingjing Zhang3†, Meng Wei1,2, Baihui Liu1,2 and Kuiran Dong1,2*
Abstract Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play various important roles in the development of cancers. The widespread applications of ribosome profiling and ribosome nascent chain complex sequencing revealed that some short open reading frames of lncRNAs have micropeptide-coding potential. The resulting micropeptides have been shown to participate in N6-methyladenosine modification, tumor angiogenesis, cancer metabolism, and signal transduction. This review summarizes current information regarding the reported roles of lncRNA-encoded micropeptides in cancer, and explores the potential clinical value of these micropeptides in the development of anti-cancer drugs and prognostic tumor biomarkers. Keywords:: lncRNA, Open reading frame, Coding potential, Micropeptide, Cancer Background The mammalian genome produces huge numbers of transcripts during the transcription process; however, about 98% of human RNA transcripts are non-coding [1]. Noncoding RNAs can be classified into microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and small nucleolar RNAs (snoRNAs), all of which have different regulatory functions[2]. Among them, lncRNAs are a class of RNAs > 200 nucleotides long that do not code for proteins[3, 4]. Dysregulation of lncRNAs has been shown to be involved in physiological processes such as the regulation of gene expression [5], chromatin remodeling [6], maintenance of pluripotency[7], DNA damage repair [8], competing endogenous RNAs [9, 10], and it also can participate in some pathological processes such as tumorigenesis [11]. Developments in next-generation sequencing and advances in bioinformatics have revealed novel insights into the roles and functions of lncRNAs, including their *Correspondence: [email protected] † Mujie Ye, Jingjing Zhang contributed equally to this work as first authors 2 Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, China Full list of author information is available at the end of the article
potential to encode functional micropeptides [12]. Functional micropeptides are usually encoded by open reading frames (ORFs) in ncRNAs, including lncRNAs, circRNAs, and pre-miRNAs [13]. Current studies on lncRNAencoded peptides in humans have mainly focused on their role in malignant tumors. These micropeptides serve as oncogenic drivers or tumor suppressors, similar to coding and noncoding genes, and play functional roles in processes including cancer onset, promotion, and progression by taking part in tumor angiogenesis, N6-methyladenosine (m6A) modification, signaling pathway transduction, and cancer metabolism[1, 14]. There are several reasons why previous studies may have failed to detect these peptides. First, micropeptides differ from conventional proteins in being very short (normally
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