Elsevier

Clinica Chimica Acta

Volume 499, December 2019, Pages 75-80
Clinica Chimica Acta

Review
Long noncoding RNA OIP5-AS1 in cancer

https://doi.org/10.1016/j.cca.2019.08.031Get rights and content

Highlights

  • Long noncoding RNAs have diverse regulatory roles in cell biology and disease.

  • OIP5-AS1 is a lncRNA that is associated with cell proliferation and tumor growth.

  • OIP5-AS1 expression affects cancer development in a cancer-specific manner.

  • OIP5-AS1 showed promising potential in cancer diagnosis, prognosis and therapy.

Abstract

Long noncoding RNAs (lncRNAs) can be over two hundred nucleotides in length and lack an obvious open reading frame (ORF). Interestingly, these RNAs form a group of nucleic acids involved in a variety of diverse cellular mechanisms involving proliferation, differentiation, apoptosis,and senescence. Given these characteristics, it is not unexpected that the aberrant expression of certain lncRNAs is strongly linked to oncogenesis and tumor advancement. OIP5-AS1, a prominent tumor-associated lncRNA, contributes to intricate cellular mechanisms during the evolution of malignant tumors. For example, it not only represses cyclin G-associated kinase (GAK) expression thus impacting mitosis, but also regulates cell proliferation and apoptosis in many cancers, including lung adenocarcinoma, breast, glioma and hepatoblastoma. In this paper, we review our current understanding of OIP5-AS1 in carcinogenesis and its potential application as a clinical biomarker or therapeutic target in malignancy.

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.

References (47)

  • J.B. Geigl et al.

    Defining “chromosomal instability”

    Trends Genet.

    (2008)
  • ENCODE Project Consortium

    An integrated encyclopedia of DNA elements in the human genome

    Nature.

    (2012)
  • T.R. Mercer et al.

    Long non-coding RNAs: insights into functions

    Nat. Rev. Genet.

    (2009)
  • L. Lorenzi et al.

    Long noncoding RNA expression profiling in cancer: challenges and opportunities

    Gene. Chromosome. Canc.

    (2019)
  • Y. Xin et al.

    CCAT1: a pivotal oncogenic long noncoding RNA in human cancers

    Cell Prolif.

    (2016)
  • H. Ling et al.

    MicroRNAs and other non-coding RNAs as targets for anticancer drug development

    Nat. Rev. Drug Discov.

    (2013)
  • L.L. Chen et al.

    Regulation of circRNA biogenesis

    RNA Biol.

    (2015)
  • E. Leucci et al.

    Melanoma addiction to the long non-coding RNA SAMMSON

    Nature.

    (2016)
  • Y. Zhang et al.

    LncRNA Sox2ot overexpression serves as a poor prognostic biomarker in gastric cancer

    Am. J. Transl. Res.

    (2016)
  • M. Naemura et al.

    The long noncoding RNA OIP5-AS1 is involved in the regulation of cell proliferation

    Anticancer Res.

    (2018)
  • J. Kim et al.

    LncRNA OIP5-AS1/cyrano sponges RNA-binding protein HuR

    Nucleic Acids Res.

    (2016)
  • J. Kim et al.

    LncRNA OIP5-AS1/cyrano suppresses GAK expression to control mitosis

    Oncotarget.

    (2017)
  • H. Zeng et al.

    Downregulation of long non-coding RNA Opa interacting protein 5-antisense RNA 1 inhibits breast cancer progression by targeting sex-determining region Y-box 2 by microRNA-129-5p upregulation

    Cancer Sci.

    (2019)
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