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Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Genome-wide analyses of long noncoding RNA expression profiles correlated with radioresistance in nasopharyngeal carcinoma via next-generation deep sequencing

Authors: Guo Li, Yong Liu, Chao Liu, Zhongwu Su, Shuling Ren, Yunyun Wang, Tengbo Deng, Donghai Huang, Yongquan Tian, Yuanzheng Qiu

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Radioresistance is one of the major factors limiting the therapeutic efficacy and prognosis of patients with nasopharyngeal carcinoma (NPC). Accumulating evidence has suggested that aberrant expression of long noncoding RNAs (lncRNAs) contributes to cancer progression. Therefore, here we identified lncRNAs associated with radioresistance in NPC.

Methods

The differential expression profiles of lncRNAs associated with NPC radioresistance were constructed by next-generation deep sequencing by comparing radioresistant NPC cells with their parental cells. LncRNA-related mRNAs were predicted and analyzed using bioinformatics algorithms compared with the mRNA profiles related to radioresistance obtained in our previous study. Several lncRNAs and associated mRNAs were validated in established NPC radioresistant cell models and NPC tissues.

Results

By comparison between radioresistant CNE-2-Rs and parental CNE-2 cells by next-generation deep sequencing, a total of 781 known lncRNAs and 2054 novel lncRNAs were annotated. The top five upregulated and downregulated known/novel lncRNAs were detected using quantitative real-time reverse transcription-polymerase chain reaction, and 7/10 known lncRNAs and 3/10 novel lncRNAs were demonstrated to have significant differential expression trends that were the same as those predicted by deep sequencing. From the prediction process, 13 pairs of lncRNAs and their associated genes were acquired, and the prediction trends of three pairs were validated in both radioresistant CNE-2-Rs and 6-10B-Rs cell lines, including lncRNA n373932 and SLITRK5, n409627 and PRSS12, and n386034 and RIMKLB. LncRNA n373932 and its related SLITRK5 showed dramatic expression changes in post-irradiation radioresistant cells and a negative expression correlation in NPC tissues (R = −0.595, p < 0.05).

Conclusions

Our study provides an overview of the expression profiles of radioresistant lncRNAs and potentially related mRNAs, which will facilitate future investigations into the function of lncRNAs in NPC radioresistance.
Appendix
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Literature
1.
go back to reference Jia WH, Huang QH, Liao J, Ye W, Shugart YY, Liu Q, et al. Trends in incidence and mortality of nasopharyngeal carcinoma over a 20–25 year period (1978/1983-2002) in Sihui and Cangwu counties in southern China. BMC Cancer. 2006;6:178.CrossRefPubMedPubMedCentral Jia WH, Huang QH, Liao J, Ye W, Shugart YY, Liu Q, et al. Trends in incidence and mortality of nasopharyngeal carcinoma over a 20–25 year period (1978/1983-2002) in Sihui and Cangwu counties in southern China. BMC Cancer. 2006;6:178.CrossRefPubMedPubMedCentral
2.
3.
go back to reference Wang WJ, Wu SP, Liu JB, Shi YS, Huang X, Zhang QB, et al. MYC regulation of CHK1 and CHK2 promotes radioresistance in a stem cell-like population of nasopharyngeal carcinoma cells. Cancer Res. 2013;73(3):1219–31.CrossRefPubMed Wang WJ, Wu SP, Liu JB, Shi YS, Huang X, Zhang QB, et al. MYC regulation of CHK1 and CHK2 promotes radioresistance in a stem cell-like population of nasopharyngeal carcinoma cells. Cancer Res. 2013;73(3):1219–31.CrossRefPubMed
4.
go back to reference Qu C, Liang Z, Huang J, Zhao R, Su C, Wang S, et al. MiR-205 determines the radioresistance of human nasopharyngeal carcinoma by directly targeting PTEN. Cell Cycle. 2012;11(4):785–96.CrossRefPubMedPubMedCentral Qu C, Liang Z, Huang J, Zhao R, Su C, Wang S, et al. MiR-205 determines the radioresistance of human nasopharyngeal carcinoma by directly targeting PTEN. Cell Cycle. 2012;11(4):785–96.CrossRefPubMedPubMedCentral
5.
go back to reference Wang Y, Yin W, Zhu X. Blocked autophagy enhances radiosensitivity of nasopharyngeal carcinoma cell line CNE-2 in vitro. Acta Otolaryngol. 2014;134(1):105–10.CrossRefPubMed Wang Y, Yin W, Zhu X. Blocked autophagy enhances radiosensitivity of nasopharyngeal carcinoma cell line CNE-2 in vitro. Acta Otolaryngol. 2014;134(1):105–10.CrossRefPubMed
7.
go back to reference Yang G, Lu X, Yuan L. LncRNA: a link between RNA and cancer. Biochim Biophys Acta. 2014;1839(11):1097–109.CrossRefPubMed Yang G, Lu X, Yuan L. LncRNA: a link between RNA and cancer. Biochim Biophys Acta. 2014;1839(11):1097–109.CrossRefPubMed
8.
go back to reference Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71(20):6320–6.CrossRefPubMed Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71(20):6320–6.CrossRefPubMed
9.
go back to reference Pang EJ, Yang R, Fu XB, Liu YF. Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer. Tumour Biol. 2015;36(4):2403–7.CrossRefPubMed Pang EJ, Yang R, Fu XB, Liu YF. Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer. Tumour Biol. 2015;36(4):2403–7.CrossRefPubMed
10.
go back to reference Shi Y, Lu J, Zhou J, Tan X, He Y, Ding J, et al. Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells. Biochem Biophys Res Commun. 2014;446(2):448–53.CrossRefPubMed Shi Y, Lu J, Zhou J, Tan X, He Y, Ding J, et al. Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells. Biochem Biophys Res Commun. 2014;446(2):448–53.CrossRefPubMed
11.
go back to reference Shen XH, Qi P, Du X. Long non-coding RNAs in cancer invasion and metastasis. Mod Pathol. 2015;28(1):4–13.CrossRefPubMed Shen XH, Qi P, Du X. Long non-coding RNAs in cancer invasion and metastasis. Mod Pathol. 2015;28(1):4–13.CrossRefPubMed
12.
go back to reference Li G, Liu Y, Su Z, Ren S, Zhu G, Tian Y, et al. MicroRNA-324-3p regulates nasopharyngeal carcinoma radioresistance by directly targeting WNT2B. Eur J Cancer. 2013;49(11):2596–607.CrossRefPubMed Li G, Liu Y, Su Z, Ren S, Zhu G, Tian Y, et al. MicroRNA-324-3p regulates nasopharyngeal carcinoma radioresistance by directly targeting WNT2B. Eur J Cancer. 2013;49(11):2596–607.CrossRefPubMed
13.
go back to reference Li G, Qiu Y, Su Z, Ren S, Liu C, Tian Y, et al. Genome-wide analyses of radioresistance-associated miRNA expression profile in nasopharyngeal carcinoma using next generation deep sequencing. PloS One. 2013;8(12):e84486.CrossRefPubMedPubMedCentral Li G, Qiu Y, Su Z, Ren S, Liu C, Tian Y, et al. Genome-wide analyses of radioresistance-associated miRNA expression profile in nasopharyngeal carcinoma using next generation deep sequencing. PloS One. 2013;8(12):e84486.CrossRefPubMedPubMedCentral
14.
go back to reference Fleige S, Walf V, Huch S, Prgomet C, Sehm J, Pfaffl MW. Comparison of relative mRNA quantification models and the impact of RNA integrity in quantitative real-time RT-PCR. Biotechnol Lett. 2006;28(19):1601–13.CrossRefPubMed Fleige S, Walf V, Huch S, Prgomet C, Sehm J, Pfaffl MW. Comparison of relative mRNA quantification models and the impact of RNA integrity in quantitative real-time RT-PCR. Biotechnol Lett. 2006;28(19):1601–13.CrossRefPubMed
15.
go back to reference Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012;7(3):562–78.CrossRefPubMedPubMedCentral Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012;7(3):562–78.CrossRefPubMedPubMedCentral
16.
go back to reference Tafer H, Hofacker IL. RNAplex: a fast tool for RNA-RNA interaction search. Bioinformatics. 2008;24(22):2657–63.CrossRefPubMed Tafer H, Hofacker IL. RNAplex: a fast tool for RNA-RNA interaction search. Bioinformatics. 2008;24(22):2657–63.CrossRefPubMed
18.
go back to reference Pelechano V, Steinmetz LM. Gene regulation by antisense transcription. Nat Rev Genet. 2013;14(12):880–93.CrossRefPubMed Pelechano V, Steinmetz LM. Gene regulation by antisense transcription. Nat Rev Genet. 2013;14(12):880–93.CrossRefPubMed
19.
go back to reference Preker P, Nielsen J, Kammler S, Lykke-Andersen S, Christensen MS, Mapendano CK, et al. RNA exosome depletion reveals transcription upstream of active human promoters. Science. 2008;322(5909):1851–4.CrossRefPubMed Preker P, Nielsen J, Kammler S, Lykke-Andersen S, Christensen MS, Mapendano CK, et al. RNA exosome depletion reveals transcription upstream of active human promoters. Science. 2008;322(5909):1851–4.CrossRefPubMed
20.
go back to reference Feng XP, Yi H, Li MY, Li XH, Yi B, Zhang PF, et al. Identification of biomarkers for predicting nasopharyngeal carcinoma response to radiotherapy by proteomics. Cancer Res. 2010;70(9):3450–62.CrossRefPubMed Feng XP, Yi H, Li MY, Li XH, Yi B, Zhang PF, et al. Identification of biomarkers for predicting nasopharyngeal carcinoma response to radiotherapy by proteomics. Cancer Res. 2010;70(9):3450–62.CrossRefPubMed
22.
go back to reference Wang G, Li Z, Zhao Q, Zhu Y, Zhao C, Li X, et al. LincRNA-p21 enhances the sensitivity of radiotherapy for human colorectal cancer by targeting the Wnt/beta-catenin signaling pathway. Oncol Rep. 2014;31(4):1839–45.PubMed Wang G, Li Z, Zhao Q, Zhu Y, Zhao C, Li X, et al. LincRNA-p21 enhances the sensitivity of radiotherapy for human colorectal cancer by targeting the Wnt/beta-catenin signaling pathway. Oncol Rep. 2014;31(4):1839–45.PubMed
23.
go back to reference Zhang H, Luo H, Hu Z, Peng J, Jiang Z, Song T, et al. Targeting WISP1 to sensitize esophageal squamous cell carcinoma to irradiation. Oncotarget. 2015;6(8):6218–34.CrossRefPubMedPubMedCentral Zhang H, Luo H, Hu Z, Peng J, Jiang Z, Song T, et al. Targeting WISP1 to sensitize esophageal squamous cell carcinoma to irradiation. Oncotarget. 2015;6(8):6218–34.CrossRefPubMedPubMedCentral
24.
go back to reference Wang Q, Fan H, Liu Y, Yin Z, Cai H, Liu J, et al. Curcumin enhances the radiosensitivity in nasopharyngeal carcinoma cells involving the reversal of differentially expressed long non-coding RNAs. Int J Oncol. 2014;44(3):858–64.PubMed Wang Q, Fan H, Liu Y, Yin Z, Cai H, Liu J, et al. Curcumin enhances the radiosensitivity in nasopharyngeal carcinoma cells involving the reversal of differentially expressed long non-coding RNAs. Int J Oncol. 2014;44(3):858–64.PubMed
25.
go back to reference Gu W, Gao T, Sun Y, Zheng X, Wang J, Ma J, et al. LncRNA expression profile reveals the potential role of lncRNAs in gastric carcinogenesis. Cancer Biomark. 2015;15:249–58.CrossRefPubMed Gu W, Gao T, Sun Y, Zheng X, Wang J, Ma J, et al. LncRNA expression profile reveals the potential role of lncRNAs in gastric carcinogenesis. Cancer Biomark. 2015;15:249–58.CrossRefPubMed
26.
go back to reference Gao Y, Chen G, Zeng Y, Zeng J, Lin M, Liu X, et al. Invasion and metastasis-related long noncoding RNA expression profiles in hepatocellular carcinoma. Tumour Biol. 2015;36:7409–22.CrossRefPubMed Gao Y, Chen G, Zeng Y, Zeng J, Lin M, Liu X, et al. Invasion and metastasis-related long noncoding RNA expression profiles in hepatocellular carcinoma. Tumour Biol. 2015;36:7409–22.CrossRefPubMed
28.
go back to reference Shi W, Zhou W. Frequency distribution of TATA Box and extension sequences on human promoters. BMC Bioinformatics. 2006;7 Suppl 4:S2.CrossRefPubMed Shi W, Zhou W. Frequency distribution of TATA Box and extension sequences on human promoters. BMC Bioinformatics. 2006;7 Suppl 4:S2.CrossRefPubMed
29.
go back to reference Shmelkov SV, Hormigo A, Jing D, Proenca CC, Bath KG, Milde T, et al. Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive-like behaviors in mice. Nat Med. 2010;16(5):598–602. 1p-602p.CrossRefPubMedPubMedCentral Shmelkov SV, Hormigo A, Jing D, Proenca CC, Bath KG, Milde T, et al. Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive-like behaviors in mice. Nat Med. 2010;16(5):598–602. 1p-602p.CrossRefPubMedPubMedCentral
30.
go back to reference Mitsui S, Osako Y, Yokoi F, Dang MT, Yuri K, Li Y, et al. A mental retardation gene, motopsin/neurotrypsin/prss12, modulates hippocampal function and social interaction. Eur J Neurosci. 2009;30(12):2368–78.CrossRefPubMedPubMedCentral Mitsui S, Osako Y, Yokoi F, Dang MT, Yuri K, Li Y, et al. A mental retardation gene, motopsin/neurotrypsin/prss12, modulates hippocampal function and social interaction. Eur J Neurosci. 2009;30(12):2368–78.CrossRefPubMedPubMedCentral
31.
go back to reference Collard F, Stroobant V, Lamosa P, Kapanda CN, Lambert DM, Muccioli GG, et al. Molecular identification of N-acetylaspartylglutamate synthase and beta-citrylglutamate synthase. J Biol Chem. 2010;285(39):29826–33.CrossRefPubMedPubMedCentral Collard F, Stroobant V, Lamosa P, Kapanda CN, Lambert DM, Muccioli GG, et al. Molecular identification of N-acetylaspartylglutamate synthase and beta-citrylglutamate synthase. J Biol Chem. 2010;285(39):29826–33.CrossRefPubMedPubMedCentral
32.
go back to reference Novikova IV, Hennelly SP, Sanbonmatsu KY. Sizing up long non-coding RNAs: do lncRNAs have secondary and tertiary structure? Bioarchitecture. 2012;2:189–99.CrossRefPubMedPubMedCentral Novikova IV, Hennelly SP, Sanbonmatsu KY. Sizing up long non-coding RNAs: do lncRNAs have secondary and tertiary structure? Bioarchitecture. 2012;2:189–99.CrossRefPubMedPubMedCentral
Metadata
Title
Genome-wide analyses of long noncoding RNA expression profiles correlated with radioresistance in nasopharyngeal carcinoma via next-generation deep sequencing
Authors
Guo Li
Yong Liu
Chao Liu
Zhongwu Su
Shuling Ren
Yunyun Wang
Tengbo Deng
Donghai Huang
Yongquan Tian
Yuanzheng Qiu
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2755-6

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