ReviewLong noncoding RNA OIP5-AS1 in cancer
Introduction
Complete genome sequencing of eukaryotes indicates that although approximately 70% of the human genome is transcribed into RNAs, <2% has protein-coding functions [1]. Such noncoding RNAs (ncRNAs) were initially regarded as transcriptional noise with no specific biological function [2]. With the advance of biotechnology, however, some ncRNAs were found to be involved in cellular processes important for normal development and physiology [3] and were classified into novel categories such as small nucleolar RNAs (snoRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) [[4], [5], [6], [7]]. LncRNAs are largely transcribed by RNA polymerase II and defined by a length >200 nucleotides with no functional open reading frame (ORF) [8,9]. In the past few years, more studies have shown lncRNAs could serve as biological modifiers of gene expression, and their misregulation is closely related to many diseases, including cancers. Therefore, studying these transcripts provides a broad prospect of identifying novel diagnostic and therapeutic targets.
The OPA-interacting protein 5 antisense transcript 1 (OIP5-AS1) is a newly identified and promising lncRNA that is located on chromosome 15q15.1 [10]. It was first recognized by Ulitsky et al. as Cyrano, which is expressed in the nervous system and notochord in zebrafish embryos and is required for the neurogenesis during embryonic development [11]. Zebrafish embryos with repressed Cyrano expression had developmental deficits, including small heads and eyes, short tails, and defects in the neural tube opening, which could be partly rescued by the injection of mature Cyrano with a conserved fragment of 67 nt that is homologous to human and mouse Cyrano genes [11]. OIP5-AS1 can suppress the proliferation of HeLa cervical cancer cells by sponging HuR, an RNA-binding protein, to sponge it from binding target mRNAs of proliferation-associated genes such as CCNA2, CCND1 and SIRT1 [12]. Thus, when the level of OIP5-AS1 decreases, the quantity of these proliferation-related proteins is higher and leads to cell proliferation. In addition, OIP5-AS1 can also control mitosis in HeLa cells by repressing GAK protein expression [13].
OIP5-AS1 has been shown to play various roles in multiple other tumors; OIP5-AS1 is strongly up-regulated in tumor samples as well as breast cancer cell lines, where it acts as an oncogene by modulating SOX2 through miR-129-5p [14]. It also encouraged malignant behavior in glioma, hepatoblastoma, lung adenocarcinoma both in vitro and in vivo experiments [[15], [16], [17]]. In the present review, we summarize the latest progress in our understanding of the OIP5-AS1 mechanism and the role of this cancer-implicated lncRNA in the occurrence and development of various malignant tumors (Table 1, Table 2).
Section snippets
Lung cancer
OIP5-AS1 expression was significantly enhanced in lung adenocarcinoma and squamous cell cancer compared to adjacent tumor-free tissues (P < .01), which was positively related with larger tumor size (P = .012) and Ki67 protein expression rate (P = .045), but not with lymph node metastasis [18]. The patients with highly up-regulated OIP5-AS1 had poorer overall survival than those with low expression levels (P = .021). Functionally, OIP5-AS1 overexpression significantly promoted tumor cell
OIP5-AS1 and microRNAs
The competing endogenous RNA (ceRNA) is a heterogeneous class of transcripts able to regulate the expression of mRNAs by competitively binding microRNAs [31]. This functional behavior was shown to be extensively involved in the regulation of malignant phenotypes of tumor cells [32]. As one of the ceRNAs, OIP5-AS1 exerts an oncogenic role in glioma by promoting the expression of Wnt-7b, which activates the Wnt-β-catenin pathway by outcompeting miR-410 [15]. In NSCLC cells, the
Conclusion and perspective
LncRNAs function through various and sophisticated molecular mechanisms; they act as a guide, scaffold, decoy or tether for other biomolecules [41,42]. Recently, considerable efforts were made to further detail their mechanisms of action, and there is increasing evidence that altered expression of lncRNA has important functions in tumor biology, such as oncogenesis, tumor advancement and metastasis, that results in uncontrolled tumor progression [43,44]. This evidence provides a new direction
Acknowledgements
The article was completed under the guidance of Professor Junqing Han and Dr. Hong Feng. We are also very grateful to our friend Hao Yin, who has provided us with a lot of help in revising the manuscript.
Funding
This work was supported by the National Natural Science Foundation of China [grant number 81201865]; Natural Science Foundation of Shandong Province [grant number ZR2017QH004].
Conflict of interest
The authors declare no conflict of interest.
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These authors contributed equally to this work.