The Functions and Unique Features of LncRNAs in Cancer Development and Tumorigenesis

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Jan 13

PMID 33435206

Citations 85

Authors

Kenzui Taniue

Nobuyoshi Akimitsu

Affiliations

Soon will be listed here.

Abstract

Over the past decades, research on cancer biology has focused on the involvement of protein-coding genes in cancer development. Long noncoding RNAs (lncRNAs), which are transcripts longer than 200 nucleotides that lack protein-coding potential, are an important class of RNA molecules that are involved in a variety of biological functions. Although the functions of a majority of lncRNAs have yet to be clarified, some lncRNAs have been shown to be associated with human diseases such as cancer. LncRNAs have been shown to contribute to many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, protein and RNA. Here we describe the literature regarding the biogenesis and features of lncRNAs. We also present an overview of the current knowledge regarding the roles of lncRNAs in cancer from the view of various aspects of cellular homeostasis, including proliferation, survival, migration and genomic stability. Furthermore, we discuss the methodologies used to identify the function of lncRNAs in cancer development and tumorigenesis. Better understanding of the molecular mechanisms involving lncRNA functions in cancer is critical for the development of diagnostic and therapeutic strategies against tumorigenesis.

Citing Articles

HOTAIR Participation in Glycolysis and Glutaminolysis Through Lactate and Glutamate Production in Colorectal Cancer.

Flores-Garcia L, Garcia-Castillo V, Perez-Toledo E, Trujano-Camacho S, Millan-Catalan O, Perez-Yepez E Cells. 2025; 14(5).

PMID: 40072116 PMC: 11898799. DOI: 10.3390/cells14050388.

The microRNA landscape and regulatory network in Clonorchis sinensis-infected hepatocellular carcinoma: implications for tumor progression.

Wei C, Chen J, Huang T, Zhou L, Xu Y, Lin Q Parasit Vectors. 2025; 18(1):68.

PMID: 39985046 PMC: 11846337. DOI: 10.1186/s13071-025-06689-z.

Long Non-Coding RNAs in Ovarian Cancer: Mechanistic Insights and Clinical Applications.

Basu S, Nadhan R, Dhanasekaran D Cancers (Basel). 2025; 17(3).

PMID: 39941838 PMC: 11815776. DOI: 10.3390/cancers17030472.

Investigating the role of exosomal long non-coding RNAs in drug resistance within female reproductive system cancers.

Shirani N, Abdi N, Chehelgerdi M, Yaghoobi H, Chehelgerdi M Front Cell Dev Biol. 2025; 13:1485422.

PMID: 39925739 PMC: 11802832. DOI: 10.3389/fcell.2025.1485422.

Oxidative stress and dysregulated long noncoding RNAs in the pathogenesis of Parkinson's disease.

Wang J, Liu M, Zhao J, Hu P, Gao L, Tian S Biol Res. 2025; 58(1):7.

PMID: 39871377 PMC: 11770960. DOI: 10.1186/s40659-025-00585-7.

References

Ke H, Zhao L, Feng X, Xu H, Zou L, Yang Q . NEAT1 is Required for Survival of Breast Cancer Cells Through FUS and miR-548. Gene Regul Syst Bio. 2016; 10(Suppl 1):11-7. PMC: 4849421. DOI: 10.4137/GRSB.S29414. View

Bhartiya D, Pal K, Ghosh S, Kapoor S, Jalali S, Panwar B . lncRNome: a comprehensive knowledgebase of human long noncoding RNAs. Database (Oxford). 2013; 2013:bat034. PMC: 3708617. DOI: 10.1093/database/bat034. View

Shtivelman E, Henglein B, Groitl P, Lipp M, Bishop J . Identification of a human transcription unit affected by the variant chromosomal translocations 2;8 and 8;22 of Burkitt lymphoma. Proc Natl Acad Sci U S A. 1989; 86(9):3257-60. PMC: 287109. DOI: 10.1073/pnas.86.9.3257. View

Wang K, Chang H . Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011; 43(6):904-14. PMC: 3199020. DOI: 10.1016/j.molcel.2011.08.018. View

Taniue K, Kurimoto A, Takeda Y, Nagashima T, Okada-Hatakeyama M, Katou Y . -TCF3 complex is required for the tumorigenicity of colorectal cancer cells. Proc Natl Acad Sci U S A. 2016; 113(45):12739-12744. PMC: 5111701. DOI: 10.1073/pnas.1605938113. View

Kim D, Kim J, Hur J, Been K, Yoon S, Kim J . Genome-wide analysis reveals specificities of Cpf1 endonucleases in human cells. Nat Biotechnol. 2016; 34(8):863-8. DOI: 10.1038/nbt.3609. View

Cui M, You L, Ren X, Zhao W, Liao Q, Zhao Y . Long non-coding RNA PVT1 and cancer. Biochem Biophys Res Commun. 2016; 471(1):10-4. DOI: 10.1016/j.bbrc.2015.12.101. View

Pattanayak V, Lin S, Guilinger J, Ma E, Doudna J, Liu D . High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nat Biotechnol. 2013; 31(9):839-43. PMC: 3782611. DOI: 10.1038/nbt.2673. View

Carthew R, Sontheimer E . Origins and Mechanisms of miRNAs and siRNAs. Cell. 2009; 136(4):642-55. PMC: 2675692. DOI: 10.1016/j.cell.2009.01.035. View

10.

Yu W, Gius D, Onyango P, Muldoon-Jacobs K, Karp J, Feinberg A . Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature. 2008; 451(7175):202-6. PMC: 2743558. DOI: 10.1038/nature06468. View

11.

Fox A, Nakagawa S, Hirose T, Bond C . Paraspeckles: Where Long Noncoding RNA Meets Phase Separation. Trends Biochem Sci. 2018; 43(2):124-135. DOI: 10.1016/j.tibs.2017.12.001. View

12.

Wienert B, Wyman S, Richardson C, Yeh C, Akcakaya P, Porritt M . Unbiased detection of CRISPR off-targets in vivo using DISCOVER-Seq. Science. 2019; 364(6437):286-289. PMC: 6589096. DOI: 10.1126/science.aav9023. View

13.

Bussemakers M, van Bokhoven A, Verhaegh G, Smit F, Karthaus H, Schalken J . DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res. 1999; 59(23):5975-9. View

14.

Cabili M, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A . Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 2011; 25(18):1915-27. PMC: 3185964. DOI: 10.1101/gad.17446611. View

15.

Quek X, Thomson D, Maag J, Bartonicek N, Signal B, Clark M . lncRNAdb v2.0: expanding the reference database for functional long noncoding RNAs. Nucleic Acids Res. 2014; 43(Database issue):D168-73. PMC: 4384040. DOI: 10.1093/nar/gku988. View

16.

Khalil A, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D . Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009; 106(28):11667-72. PMC: 2704857. DOI: 10.1073/pnas.0904715106. View

17.

Kretz M, Siprashvili Z, Chu C, Webster D, Zehnder A, Qu K . Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature. 2012; 493(7431):231-5. PMC: 3674581. DOI: 10.1038/nature11661. View

18.

Shtivelman E, Bishop J . The PVT gene frequently amplifies with MYC in tumor cells. Mol Cell Biol. 1989; 9(3):1148-54. PMC: 362705. DOI: 10.1128/mcb.9.3.1148-1154.1989. View

19.

Zhang F, Wu L, Qian J, Qu B, Xia S, La T . Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus. J Autoimmun. 2016; 75:96-104. DOI: 10.1016/j.jaut.2016.07.012. View

20.

Engreitz J, Pandya-Jones A, McDonel P, Shishkin A, Sirokman K, Surka C . The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science. 2013; 341(6147):1237973. PMC: 3778663. DOI: 10.1126/science.1237973. View