Differential expression of microRNAs and their target genes in non-small-cell lung cancer

Lee,Hui-Young; Han,Seon-Sook; Rhee,Hwanseok; Park,Jung  Hoon; Lee,Jae  Seung; Oh,Yeon-Mok; Choi,Sun  Shim; Shin,Seung-Ho; Kim,Woo  Jin

doi:10.3892/mmr.2014.2890

Differential expression of microRNAs and their target genes in non-small-cell lung cancer

Authors:
- Hui-Young Lee
- Seon-Sook Han
- Hwanseok Rhee
- Jung Hoon Park
- Jae Seung Lee
- Yeon-Mok Oh
- Sun Shim Choi
- Seung-Ho Shin
- Woo Jin Kim
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Affiliations: Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 200-722, Republic of Korea, Macrogen Bioinformatics Center, Macrogen, Seoul 153-023, Republic of Korea, Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea, Department of Medical Biotechnology, College of Biomedical Science and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon-si, Gangwon-do 200-701, Republic of Korea
Published online on: November 6, 2014 https://doi.org/10.3892/mmr.2014.2890
Pages: 2034-2040

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Abstract

MicroRNAs (miRNAs) are single‑stranded RNA species that constitute a class of non‑coding RNAs, and are emerging as key regulators of gene expression. Since each miRNA is capable of regulating multiple genes, miRNAs are attractive markers for studies of coordinated gene expression. In this study, we investigated miRNA expression profiling using a massively parallel sequencing technique to compare non‑small‑cell lung cancer (NSCLC) tissue and normal lung tissue. Lung cancer tissue and normal lung tissue were obtained from nine NSCLC patients. RNA isolated from these samples was processed using RNA sequencing (RNA Seq) and the HiSeq 2000 system. Differentially expressed miRNAs and mRNAs were analyzed using a t‑test. We selected target pairs that showed a negative correlation among significantly differentially expressed miRNAs and their putative target mRNAs using miRBase Targets. The differences in the expression levels of 222 miRNAs and 1,597 genes were statistically significant, as indicated by an absolute fold change ≥1.5 and P<0.05. miR‑577, miR‑301b, miR‑944, miR‑891a and miR‑615‑3p were generally upregulated, and miR‑338‑3p was generally downregulated. miRNA‑mRNA target pair analysis revealed that 49 miRNAs had 696 target mRNAs. There were significantly differentially expressed miRNAs and mRNAs between lung cancer and normal tissue. Further investigation of miRNAs and their target genes is warranted to better understand NSCLC.

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1	Võsa U, Vooder T, Kolde R, et al: Meta-analysis of microRNA expression in lung cancer. Int J Cancer. 132:2884–2893. 2013. View Article : Google Scholar
2	Jemal A, Bray F, Center MM, et al: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
3	Esteller M: Non-coding RNAs in human disease. Nat Rev Genet. 12:861–874. 2011. View Article : Google Scholar : PubMed/NCBI
4	Iorio MV, Ferracin M, Liu GC, et al: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65:7065–7070. 2005. View Article : Google Scholar : PubMed/NCBI
5	Yanaihara N, Caplen N, Bowman E, et al: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 9:189–198. 2006. View Article : Google Scholar : PubMed/NCBI
6	Porkka KP, Pfeiffer MJ, Waltering KK, et al: MicroRNA expression profiling in prostate cancer. Cancer Res. 67:6130–6135. 2007. View Article : Google Scholar : PubMed/NCBI
7	Akao Y, Nakagawa Y and Naoe T: MicroRNA-143 and -145 in colon cancer. DNA Cell Biol. 26:311–320. 2007. View Article : Google Scholar : PubMed/NCBI
8	Yang H, Kong W, He L, et al: MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 68:425–433. 2008. View Article : Google Scholar : PubMed/NCBI
9	Sablok G, Milev I, Minkov G, et al: isomiRex: web-based identification of microRNAs, isomiR variations and differential expression using next-generation sequencing datasets. FEBS Lett. 587:2629–2634. 2013. View Article : Google Scholar : PubMed/NCBI
10	Trapnell C, Roberts A, Goff L, et al: Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nature protocols. 7:562–578. 2012. View Article : Google Scholar : PubMed/NCBI
11	Bindea G, Mlecnik B, Hackl H, et al: ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 25:1091–1093. 2009. View Article : Google Scholar : PubMed/NCBI
12	Shannon P, Markiel A, Ozier O, et al: Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Re. 13:2498–2504. 2003. View Article : Google Scholar
13	Bindea G, Galon J and Mlecnik B: CluePedia Cytoscape plugin: Pathway insights using integrated experimental and in silico data. Bioinformatics. 29:661–663. 2013. View Article : Google Scholar : PubMed/NCBI
14	Kozomara A and Griffiths-Jones S: miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 39(Database issue): D152–D157. 2011. View Article : Google Scholar :
15	Xiao F, Zuo Z, Cai G, et al: miRecords: an integrated resource for microRNA-target interactions. Nucleic Acids Res. 37(Database issue): D105–D110. 2009. View Article : Google Scholar :
16	Albig AR, Neil JR and Schiemann WP: Fibulins 3 and 5 antagonize tumor angiogenesis in vivo. Cancer Res. 66:2621–2629. 2006. View Article : Google Scholar : PubMed/NCBI
17	Yue W, Dacic S, Sun Q, et al: Frequent inactivation of RAMP2, EFEMP1 and Dutt1 in lung cancer by promoter hypermethylation. Clin Cancer Res. 13:4336–4344. 2007. View Article : Google Scholar : PubMed/NCBI
18	Raman V, Martensen SA, Reisman D, et al: Compromised HOXA5 function can limit p53 expression in human breast tumours. Nature. 405:974–978. 2000. View Article : Google Scholar : PubMed/NCBI
19	Liu X, Lu K, Wang K, et al: MicroRNA-196a promotes non-small cell lung cancer cell proliferation and invasion through targeting HOXA5. BMC Cancer. 12:348. 2012. View Article : Google Scholar : PubMed/NCBI
20	Schraml P, Shipman R, Colombi M and Ludwig CU: Identification of genes differentially expressed in normal lung and non-small cell lung carcinoma tissue. Cancer Res. 54:5236–5240. 1994.PubMed/NCBI
21	Yu S, Yu J, Ge W, et al: SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer. World J Gastroenterol. 17:2028–2036. 2011. View Article : Google Scholar : PubMed/NCBI
22	Anedchenko EA, Dmitriev AA, Krasnov GS, et al: Down-regulation of RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1 and HYAL2 genes in non-small cell lung cancer. Mol Biol. 42:965–976. 2008.(in Russian). View Article : Google Scholar
23	Cheung W, Zhao M, Liu Z, et al: Control of alveolar differentiation by the lineage transcription factors GATA6 and HOPX inhibits lung adenocarcinoma metastasis. Cancer Cell. 23:725–738. 2013. View Article : Google Scholar : PubMed/NCBI
24	Zhou M, Du Y, Liu Y, et al: Clinical and experimental studies regarding the expression and diagnostic value of carcinoembryonic antigen-related cell adhesion molecule 1 in non-small-cell-lung cancer. BMC Cancer. 13:3592013. View Article : Google Scholar
25	Kikuchi J, Kinoshita I, Shimizu Y, et al: Minichromosome maintenance (MCM) protein 4 as a marker for proliferation and its clinical and clinicopathological significance in non-small cell lung cancer. Lung Cancer. 72:229–237. 2011. View Article : Google Scholar
26	Guan P, Yin Z, Li X, et al: Meta-analysis of human lung cancer microRNA expression profiling studies comparing cancer tissues with normal tissues. J Exp Clin Cancer Res. 31:542012. View Article : Google Scholar : PubMed/NCBI
27	Grosso S, Doyen J, Parks SK, et al: MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines. Cell Death Dis. 4:e5442013. View Article : Google Scholar : PubMed/NCBI