Long Non-coding RNAs and Their Roles in Non-small-cell Lung Cancer

As a leading cause of cancer deaths worldwide, lung cancer is a collection of diseases with diverse etiologies which can be broadly classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Lung cancer is characterized by genomic and epigenomic alterations; however, mechanisms underlying lung tumorigenesis remain to be elucidated. Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs that consist of ⩾200 nucleotides but possess low or no protein-coding potential. Accumulating evidence indicates that abnormal expression of lncRNAs is associated with tumorigenesis of various cancers, including lung cancer, through multiple biological mechanisms involving epigenetic, transcriptional, and post-transcriptional alterations. In this review, we highlight the expression and roles of lncRNAs in NSCLC and discuss their potential clinical applications as diagnostic or prognostic biomarkers, as well as therapeutic targets.

[1]  J Ma,et al.  MicroRNA and drug resistance , 2010, Cancer Gene Therapy.

[2]  L. Rothblum,et al.  SnRNAs, SnRNPs, and RNA processing. , 1982, Annual review of biochemistry.

[3]  Guang-Biao Zhou,et al.  Long non-coding RNA stabilizes the Y-box-binding protein 1 and regulates the epidermal growth factor receptor to promote lung carcinogenesis , 2016, Oncotarget.

[4]  Jing Zhang,et al.  A novel long noncoding RNA LINC01133 is upregulated in lung squamous cell cancer and predicts survival , 2015, Tumor Biology.

[5]  Z. Zeng,et al.  AFAP1-AS1, a long noncoding RNA upregulated in lung cancer and promotes invasion and metastasis , 2015, Tumor Biology.

[6]  W. Richter,et al.  Regulation of H19 and its encoded microRNA-675 in osteoarthritis and under anabolic and catabolic in vitro conditions , 2012, Journal of Molecular Medicine.

[7]  Jie Chen,et al.  Long Noncoding RNA Expression Profiles of Lung Adenocarcinoma Ascertained by Microarray Analysis , 2014, PloS one.

[8]  H. Hansen,et al.  Lung cancer. , 1990, Cancer chemotherapy and biological response modifiers.

[9]  T. D. de Reijke,et al.  Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer. , 2014, European urology.

[10]  Comparison of the miRNome and piRNome of bovine blood and plasma by small RNA sequencing , 2015, Biotechnology Letters.

[11]  F. Liu,et al.  A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma. , 2014, Cancer cell.

[12]  Li Liu,et al.  Regulation of lncRNA expression , 2014, Cellular & Molecular Biology Letters.

[13]  Xing Chen,et al.  LncRNADisease: a database for long-non-coding RNA-associated diseases , 2012, Nucleic Acids Res..

[14]  Carolyn J. Brown,et al.  The human XIST gene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus , 1992, Cell.

[15]  Lei Chen,et al.  Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer , 2014, Journal of Neuro-Oncology.

[16]  Gongcheng Hu,et al.  Functional role and mechanism of lncRNA LOC728228 in malignant 16HBE cells transformed by anti‐benzopyrene‐trans‐7,8‐dihydrodiol‐9,10‐epoxide , 2015, Molecular carcinogenesis.

[17]  David E. Leib,et al.  Evf2 (Dlx6as) lncRNA regulates ultraconserved enhancer methylation and the differential transcriptional control of adjacent genes , 2013, Development.

[18]  Jing Liu,et al.  The Long Noncoding RNA HOTAIR Contributes to Cisplatin Resistance of Human Lung Adenocarcinoma Cells via downregualtion of p21WAF1/CIP1 Expression , 2013, PloS one.

[19]  Hongwei Ma,et al.  Plasma HULC as a Promising Novel Biomarker for the Detection of Hepatocellular Carcinoma , 2013, BioMed research international.

[20]  R. Kong,et al.  EZH2-mediated epigenetic suppression of long noncoding RNA SPRY4-IT1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial–mesenchymal transition , 2014, Cell Death and Disease.

[21]  U. A. Ørom,et al.  MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation. , 2008, Molecular cell.

[22]  E. Zhang,et al.  A novel lncRNA, LUADT1, promotes lung adenocarcinoma proliferation via the epigenetic suppression of p27 , 2015, Cell Death and Disease.

[23]  Rui Hu,et al.  LncRNA HMlincRNA717 is down-regulated in non-small cell lung cancer and associated with poor prognosis. , 2014, International journal of clinical and experimental pathology.

[24]  R. Kong,et al.  Low expression of long noncoding RNA GAS6-AS1 predicts a poor prognosis in patients with NSCLC , 2013, Medical Oncology.

[25]  Howard Y. Chang,et al.  Molecular mechanisms of long noncoding RNAs. , 2011, Molecular cell.

[26]  Ming Sun,et al.  Long Noncoding RNA ANRIL Promotes Non–Small Cell Lung Cancer Cell Proliferation and Inhibits Apoptosis by Silencing KLF2 and P21 Expression , 2014, Molecular Cancer Therapeutics.

[27]  David G. Knowles,et al.  The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression , 2012, Genome research.

[28]  R. Simpson Structure and function of chromatin. , 1973, Advances in enzymology and related areas of molecular biology.

[29]  Hongzhe Li,et al.  A functional genomic approach identifies FAL1 as an oncogenic long noncoding RNA that associates with BMI1 and represses p21 expression in cancer. , 2014, Cancer cell.

[30]  P. Sharp,et al.  Spliced segments at the 5′ terminus of adenovirus 2 late mRNA* , 1977, Proceedings of the National Academy of Sciences.

[31]  K. Jöckel,et al.  Evaluation of long noncoding RNA MALAT1 as a candidate blood-based biomarker for the diagnosis of non-small cell lung cancer , 2013, BMC Research Notes.

[32]  David C. Smith,et al.  Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. , 2012, The New England journal of medicine.

[33]  E. Birney,et al.  Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs , 2002, Nature.

[34]  M. Hentze,et al.  Mechanism of translational regulation by miR-2 from sites in the 5' untranslated region or the open reading frame. , 2010, RNA.

[35]  Junfeng Geng,et al.  Combined identification of long non-coding RNA XIST and HIF1A-AS1 in serum as an effective screening for non-small cell lung cancer. , 2015, International journal of clinical and experimental pathology.

[36]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[37]  Wenya Li,et al.  The long non-coding RNA, GAS5, enhances gefitinib-induced cell death in innate EGFR tyrosine kinase inhibitor-resistant lung adenocarcinoma cells with wide-type EGFR via downregulation of the IGF-1R expression , 2015, Journal of Hematology & Oncology.

[38]  Christopher R. Cabanski,et al.  Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer , 2014, Genome Biology.

[39]  Tao Hu,et al.  BCYRN1, a c-MYC-activated long non-coding RNA, regulates cell metastasis of non-small-cell lung cancer , 2015, Cancer Cell International.

[40]  V. Anagnostou,et al.  Cancer Immunotherapy: A Future Paradigm Shift in the Treatment of Non–Small Cell Lung Cancer , 2015, Clinical Cancer Research.

[41]  Z. Fu,et al.  Systematic gene microarray analysis of the lncRNA expression profiles in human uterine cervix carcinoma. , 2015, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[42]  Joshua J. Forman,et al.  A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence , 2008, Proceedings of the National Academy of Sciences.

[43]  Yong Yang,et al.  The Noncoding RNA Expression Profile and the Effect of lncRNA AK126698 on Cisplatin Resistance in Non-Small-Cell Lung Cancer Cell , 2013, PloS one.

[44]  Xuefei Shi,et al.  The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung adenocarcinoma , 2015, Oncotarget.

[45]  E. Dees,et al.  The product of the H19 gene may function as an RNA , 1990, Molecular and cellular biology.

[46]  Lin Xu,et al.  Differentially expressed protein-coding genes and long noncoding RNA in early-stage lung cancer , 2015, Tumor Biology.

[47]  P. Xiong,et al.  Long non-coding RNA functions in lung cancer , 2015, Tumor Biology.

[48]  D. Holmes,et al.  Chromosomal RNA: Its Properties , 1972, Science.

[49]  R. Kong,et al.  Low expression of long noncoding RNA PANDAR predicts a poor prognosis of non-small cell lung cancer and affects cell apoptosis by regulating Bcl-2 , 2015, Cell Death and Disease.

[50]  L. Tang,et al.  Long non-coding RNA CARLo-5 is a negative prognostic factor and exhibits tumor pro-oncogenic activity in non-small cell lung cancer , 2014, Tumor Biology.

[51]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[52]  B. Shan,et al.  Functions of lncRNA HOTAIR in lung cancer , 2014, Journal of Hematology & Oncology.

[53]  Jiancheng Luo,et al.  Comprehensive characterization of cancer subtype associated long non-coding RNAs and their clinical implications , 2014, Scientific Reports.

[54]  J. Brosius,et al.  Expression of neural BC200 RNA in human tumours , 1997, The Journal of pathology.

[55]  Rong Yin,et al.  CCAT2 is a lung adenocarcinoma-specific long non-coding RNA and promotes invasion of non-small cell lung cancer , 2014, Tumor Biology.

[56]  Xian-jun Feng,et al.  Increased expression of the lncRNA PVT1 promotes tumorigenesis in non-small cell lung cancer. , 2014, International journal of clinical and experimental pathology.

[57]  V. Rusch,et al.  Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial , 2009, The Lancet.

[58]  David Harrington,et al.  Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. , 2002, The New England journal of medicine.

[59]  I. Seim,et al.  Identification of a long non-coding RNA gene, growth hormone secretagogue receptor opposite strand, which stimulates cell migration in non-small cell lung cancer cell lines. , 2013, International journal of oncology.

[60]  Weifeng Gu,et al.  Suppression of pervasive noncoding transcription in embryonic stem cells by esBAF , 2015, Genes & development.

[61]  T. Kwok,et al.  Riboregulator H19 induction of MDR1-associated drug resistance in human hepatocellular carcinoma cells , 2007, Oncogene.

[62]  J. Yunis,et al.  Localization of chromosomal RNA in human G-banded metaphase chromosomes. , 1977, Experimental cell research.

[63]  S. Ohno,et al.  So much "junk" DNA in our genome. , 1972, Brookhaven symposia in biology.

[64]  D. Tollervey,et al.  A ncRNA modulates histone modification and mRNA induction in the yeast GAL gene cluster. , 2008, Molecular cell.

[65]  Xiongwen Yang,et al.  The Efficacy and Safety of EGFR Inhibitor Monotherapy in Non-Small Cell Lung Cancer: A Systematic Review , 2014, Current Oncology Reports.

[66]  Yiguo Jiang,et al.  LncRNA-DQ786227-mediated cell malignant transformation induced by benzo(a)pyrene. , 2013, Toxicology letters.

[67]  Michael F. Lin,et al.  Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals , 2009, Nature.

[68]  Zhibo Hou,et al.  Long Noncoding RNAs Expression Patterns Associated with Chemo Response to Cisplatin Based Chemotherapy in Lung Squamous Cell Carcinoma Patients , 2014, PloS one.

[69]  Dominic P. Norris,et al.  The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus , 1992, Cell.

[70]  Haixiu Yang,et al.  A potential signature of eight long non-coding RNAs predicts survival in patients with non-small cell lung cancer , 2015, Journal of Translational Medicine.

[71]  C. A. Thomas The genetic organization of chromosomes. , 1971, Annual review of genetics.

[72]  Runsheng Chen,et al.  Functional Characterization of Long Noncoding RNA Lnc_bc060912 in Human Lung Carcinoma Cells. , 2015, Biochemistry.

[73]  A. Jemal,et al.  Global cancer statistics, 2012 , 2015, CA: a cancer journal for clinicians.

[74]  Jing Liu,et al.  The Long Noncoding RNA MEG3 Contributes to Cisplatin Resistance of Human Lung Adenocarcinoma , 2015, PloS one.

[75]  Cesare Furlanello,et al.  A promoter-level mammalian expression atlas , 2015 .

[76]  D. Cacchiarelli,et al.  A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA , 2011, Cell.

[77]  Thomas E. Royce,et al.  Global Identification of Human Transcribed Sequences with Genome Tiling Arrays , 2004, Science.

[78]  C. Ponting,et al.  Evolution and Functions of Long Noncoding RNAs , 2009, Cell.

[79]  Zhibo Hou,et al.  A long noncoding RNA Sox2ot regulates lung cancer cell proliferation and is a prognostic indicator of poor survival. , 2014, The international journal of biochemistry & cell biology.

[80]  J. Brosens,et al.  Physical Interaction and Mutual Transrepression between CCAAT/Enhancer-binding Protein β and the p53 Tumor Suppressor* , 2006, Journal of Biological Chemistry.

[81]  Rui Xia,et al.  Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transition , 2014, Molecular Cancer.

[82]  Xuefei Shi,et al.  A critical role for the long non‐coding RNA GAS5 in proliferation and apoptosis in non‐small‐cell lung cancer , 2015, Molecular carcinogenesis.

[83]  B. Blencowe,et al.  The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. , 2010, Molecular cell.

[84]  Juan Li,et al.  Study on expression of lncRNA RGMB-AS1 and repulsive guidance molecule b in non-small cell lung cancer , 2015, Diagnostic Pathology.

[85]  F. Bray,et al.  International lung cancer trends by histologic type: Male:Female differences diminishing and adenocarcinoma rates rising , 2005, International journal of cancer.

[86]  J. Gall,et al.  Chromosome structure and the C-value paradox , 1981, The Journal of cell biology.

[87]  Elisabeth Brambilla,et al.  DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. , 2006, The New England journal of medicine.

[88]  R. Govindan,et al.  Trends in Stage Distribution for Patients with Non-small Cell Lung Cancer: A National Cancer Database Survey , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[89]  Sarah Geisler,et al.  RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts , 2013, Nature Reviews Molecular Cell Biology.

[90]  R. Kong,et al.  P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression , 2014, Cell Death and Disease.

[91]  A. Jemal,et al.  Global Cancer Statistics , 2011 .

[92]  Roy S Herbst,et al.  KRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer , 2007, Clinical Cancer Research.

[93]  S. Orkin,et al.  Opposing Roles for the lncRNA Haunt and Its Genomic Locus in Regulating HOXA Gene Activation during Embryonic Stem Cell Differentiation. , 2015, Cell stem cell.

[94]  R. Wu,et al.  Characterization of a novel long noncoding RNA, SCAL1, induced by cigarette smoke and elevated in lung cancer cell lines. , 2013, American journal of respiratory cell and molecular biology.

[95]  R. Weikard,et al.  Identification of novel transcripts and noncoding RNAs in bovine skin by deep next generation sequencing , 2013, BMC Genomics.

[96]  J. Rinn,et al.  Modular regulatory principles of large non-coding RNAs , 2012, Nature.

[97]  Jingcheng Yang,et al.  Analysis of lncRNA expression profiles in non-small cell lung cancers (NSCLC) and their clinical subtypes. , 2014, Lung cancer.

[98]  Renato Martins,et al.  Non-small cell lung cancer, version 2.2013: Featured updates to the NCCN guidelines , 2013 .

[99]  Guoqiang Zhao,et al.  Expression of long non-coding RNA DLX6-AS1 in lung adenocarcinoma , 2015, Cancer Cell International.

[100]  G. Pan,et al.  Enhanced expression of long non-coding RNA ZXF1 promoted the invasion and metastasis in lung adenocarcinoma. , 2014, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[101]  N. Nomura,et al.  Complete sequencing and characterization of 21,243 full-length human cDNAs , 2004, Nature Genetics.

[102]  Carolyn J. Brown,et al.  The functional role of long non-coding RNA in human carcinomas , 2011, Molecular Cancer.