HOTAIRM1 as a potential biomarker for diagnosis of colorectal cancer functions the role in the tumour suppressor

Recent studies have revealed many different long noncoding RNAs (lncRNA), however, the investigation for their function and clinical value as tumour biomarkers has scarcely begun. Here, we found that expression of HOTAIRM1 was reduced in colorectal cancer (CRC) tissues compared with matched normal tissues, and plasma HOTAIRM1 levels in CRC patients were less than in controls. The cut‐off point was chosen as 0.003 with a sensitivity of 64.00% and a specificity of 76.50% in the validation set. The performance of HOTAIRM1 was highly comparable to carcinoembryonic antigen (CEA), and better than CA19‐9 and CA125. The combined assay of HOTAIRM1 and CEA raised the sensitivity and specificity to 84.00%. HOTAIRM1 knockdown resulted in obvious changes in expression of the cell proliferation related to genes and promoted cell proliferation. HOTAIRM1 plays a role of tumour suppressor in CRC; Down‐regulation of HOTAIRM1 can serve as a biomarker for CRC, and combined HOTAIRM1 and CEA assay might provide a promising diagnosis for CRC.

[1]  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.

[2]  Gary D Bader,et al.  A travel guide to Cytoscape plugins , 2012, Nature Methods.

[3]  K. Zatloukal,et al.  Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. , 2007, Gastroenterology.

[4]  Mustafa Işın,et al.  LncRNAs and neoplasia. , 2015, Clinica chimica acta; international journal of clinical chemistry.

[5]  D. Bartel,et al.  lincRNAs: Genomics, Evolution, and Mechanisms , 2013, Cell.

[6]  J. C. Tsang,et al.  Circulating nucleic acids in plasma/serum , 2007, Pathology.

[7]  J. Mattick,et al.  Long non-coding RNAs: insights into functions , 2009, Nature Reviews Genetics.

[8]  S. Hanash,et al.  Emerging molecular biomarkers—blood-based strategies to detect and monitor cancer , 2011, Nature Reviews Clinical Oncology.

[9]  Li Li,et al.  Plasma lysophosphatidylcholine levels: potential biomarkers for colorectal cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  Howard Y. Chang,et al.  Long noncoding RNAs and human disease. , 2011, Trends in cell biology.

[11]  M. Gerstein,et al.  A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster. , 2009, Blood.

[12]  J. Marks,et al.  Development of a multimarker assay for early detection of ovarian cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  E. DeLong,et al.  Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. , 1988, Biometrics.

[14]  Reuven Agami,et al.  Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA , 2015, Nature Communications.

[15]  Michael Thomas,et al.  MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer , 2003, Oncogene.

[16]  Howard Y. Chang,et al.  Extensive and coordinated transcription of noncoding RNAs within cell cycle promoters , 2011, Nature Genetics.

[17]  Min-hui Yang,et al.  MALAT-1: a long non-coding RNA and its important 3' end functional motif in colorectal cancer metastasis. , 2011, International journal of oncology.

[18]  J. Rinn,et al.  Large non-coding RNAs: missing links in cancer? , 2010, Human molecular genetics.

[19]  Daniel B. Martin,et al.  Circulating microRNAs as stable blood-based markers for cancer detection , 2008, Proceedings of the National Academy of Sciences.

[20]  Howard Y. Chang,et al.  Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis , 2010, Nature.

[21]  L. Påhlman,et al.  Growth differentiation factor 15: a prognostic marker for recurrence in colorectal cancer , 2011, British Journal of Cancer.

[22]  J. Rinn,et al.  A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response , 2010, Cell.

[23]  Alicia Algeciras-Schimnich,et al.  Analysis of circulating microRNA: preanalytical and analytical challenges. , 2011, Clinical chemistry.

[24]  Klaus Pantel,et al.  Cell-free nucleic acids as biomarkers in cancer patients , 2011, Nature Reviews Cancer.

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

[26]  P. Fraser,et al.  No-Nonsense Functions for Long Noncoding RNAs , 2011, Cell.

[27]  Howard Y. Chang,et al.  Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs , 2007, Cell.

[28]  L. Maquat,et al.  lncRNAs transactivate Staufen1-mediated mRNA decay by duplexing with 3'UTRs via Alu elements , 2010, Nature.

[29]  Bhanu P. Jena,et al.  Journal of Cellular and Molecular Medicine , 2014, Journal of Cellular and Molecular Medicine.