Genome-wide profiling of long non-coding RNA expression patterns in anthracycline-resistant breast cancer cells

He,Dong-Xu; Zhang,Guang-Yuan; Gu,Xiao-Ting; Mao,Ai-Qin; Lu,Chun-Xiao; Jin,Jian; Liu,De-Quan; Ma,Xin

doi:10.3892/ijo.2016.3665

Genome-wide profiling of long non-coding RNA expression patterns in anthracycline-resistant breast cancer cells

Authors:
- Dong-Xu He
- Guang-Yuan Zhang
- Xiao-Ting Gu
- Ai-Qin Mao
- Chun-Xiao Lu
- Jian Jin
- De-Quan Liu
- Xin Ma
View Affiliations

Affiliations: National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China, Department of Cellular and Molecular Pharmacology, School of Medicine and Pharmaceutics, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China, Department of Breast Surgery, The Third Affiliated Hospital, Kunming Medical University, Kunming, Yunnan 650031, P.R. China
Published online on: August 22, 2016 https://doi.org/10.3892/ijo.2016.3665
Pages: 1695-1703

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Long non-coding RNAs (lncRNAs) are involved in cancer progression. In the present study, we analyzed the lncRNA profiles in adriamycin-resistant and -sensitive breast cancer cells and found a group of dysregulated lncRNAs in the adriamycin-resistant cells. Expression of the dysregulated lncRNAs was correlated with dysregulated mRNAs, and these were enriched in GO and KEGG pathways associated with cancer progression and chemoresistance development. Among these lncRNA-mRNA interactions, some lncRNAs may cis‑regulate neighboring protein-coding genes and be involved in chemoresistance. We then validated that the lncRNA NONHSAT028712 regulated nearby CDK2 and interfered with the cell cycle and chemoresistance. Furthermore, we identified another group of lncRNAs that trans-regulated genes by interacting with different transcription factors. For example, NONHSAT057282 and NONHSAG023333 modulated chemoresistance and most likely interacted with the transcription factors ELF1 and E2F1, respectively. In conclusion, in the present study, we report for the first time the lncRNA expression patterns in adriamycin-resistant breast cancer cells, and provide a group of novel lncRNA targets that mediate chemoresistance development in both cis- and trans-action modes.

View Figures

View References

1	Marques AC, Hughes J, Graham B, Kowalczyk MS, Higgs DR and Ponting CP: Chromatin signatures at transcriptional start sites separate two equally populated yet distinct classes of intergenic long noncoding RNAs. Genome Biol. 14:R1312013. View Article : Google Scholar : PubMed/NCBI
2	Louro R, Smirnova AS and Verjovski-Almeida S: Long intronic noncoding RNA transcription: Expression noise or expression choice? Genomics. 93:291–298. 2009. View Article : Google Scholar
3	Lam MT, Cho H, Lesch HP, Gosselin D, Heinz S, Tanaka-Oishi Y, Benner C, Kaikkonen MU, Kim AS, Kosaka M, et al: Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription. Nature. 498:511–515. 2013. View Article : Google Scholar : PubMed/NCBI
4	Li W, Notani D, Ma Q, Tanasa B, Nunez E, Chen AY, Merkurjev D, Zhang J, Ohgi K, Song X, et al: Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature. 498:516–520. 2013. View Article : Google Scholar : PubMed/NCBI
5	Vance KW and Ponting CP: Transcriptional regulatory functions of nuclear long noncoding RNAs. Trends Genet. 30:348–355. 2014. View Article : Google Scholar : PubMed/NCBI
6	Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, et al: Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 464:1071–1076. 2010. View Article : Google Scholar : PubMed/NCBI
7	Ji P, Diederichs S, Wang W, Böing S, Metzger R, Schneider PM, Tidow N, Brandt B, Buerger H, Bulk E, et al: MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 22:8031–8041. 2003. View Article : Google Scholar : PubMed/NCBI
8	Qiu MT, Hu JW, Yin R and Xu L: Long noncoding RNA: An emerging paradigm of cancer research. Tumour Biol. 34:613–620. 2013. View Article : Google Scholar : PubMed/NCBI
9	He DX, Gu F, Gao F, Hao JJ, Gong D, Gu XT, Mao AQ, Jin J, Fu L and Ma X: Genome-wide profiles of methylation, microRNAs, and gene expression in chemoresistant breast cancer. Sci Rep. 6:247062016. View Article : Google Scholar : PubMed/NCBI
10	Adam L, Zhong M, Choi W, Qi W, Nicoloso M, Arora A, Calin G, Wang H, Siefker-Radtke A, McConkey D, et al: miR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy. Clin Cancer Res. 15:5060–5072. 2009. View Article : Google Scholar : PubMed/NCBI
11	Chan YC, Khanna S, Roy S and Sen CK: miR-200b targets Ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells. J Biol Chem. 286:2047–2056. 2011. View Article : Google Scholar :
12	Feng X, Wang Z, Fillmore R and Xi Y: MiR-200, a new star miRNA in human cancer. Cancer Lett. 344:166–173. 2014. View Article : Google Scholar :
13	Neves R, Scheel C, Weinhold S, Honisch E, Iwaniuk KM, Trompeter HI, Niederacher D, Wernet P, Santourlidis S and Uhrberg M: Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells. BMC Res Notes. 3:2192010. View Article : Google Scholar : PubMed/NCBI
14	Peter ME: Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle. 8:843–852. 2009. View Article : Google Scholar : PubMed/NCBI
15	Lee JT: Epigenetic regulation by long noncoding RNAs. Science. 338:1435–1439. 2012. View Article : Google Scholar : PubMed/NCBI
16	Mercer TR and Mattick JS: Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol. 20:300–307. 2013. View Article : Google Scholar : PubMed/NCBI
17	Ma X, Cai Y, He D, Zou C, Zhang P, Lo CY, Xu Z, Chan FL, Yu S, Chen Y, et al: Transient receptor potential channel TRPC5 is essential for P-glycoprotein induction in drug-resistant cancer cells. Proc Natl Acad Sci USA. 109:16282–16287. 2012. View Article : Google Scholar : PubMed/NCBI
18	Li Y, Wang T, Li Y, Chen D, Yu Z, Jin L, Ni L, Yang S, Mao X, Gui Y, et al: Identification of long-non coding RNA UCA1 as an oncogene in renal cell carcinoma. Mol Med Rep. 13:3326–3334. 2016.PubMed/NCBI
19	Wang XS, Zhang Z, Wang HC, Cai JL, Xu QW, Li MQ, Chen YC, Qian XP, Lu TJ, Yu LZ, et al: Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clin Cancer Res. 12:4851–4858. 2006. View Article : Google Scholar : PubMed/NCBI
20	Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F and Williams GT: GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene. 28:195–208. 2009. View Article : Google Scholar
21	Panzitt K, Tschernatsch MM, Guelly C, Moustafa T, Stradner M, Strohmaier HM, Buck CR, Denk H, Schroeder R, Trauner M, et al: Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology. 132:330–342. 2007. View Article : Google Scholar : PubMed/NCBI
22	Braconi C, Kogure T, Valeri N, Huang N, Nuovo G, Costinean S, Negrini M, Miotto E, Croce CM and Patel T: microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. Oncogene. 30:4750–4756. 2011. View Article : Google Scholar : PubMed/NCBI
23	Khaitan D, Dinger ME, Mazar J, Crawford J, Smith MA, Mattick JS and Perera RJ: The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. Cancer Res. 71:3852–3862. 2011. View Article : Google Scholar : PubMed/NCBI
24	Ellis BC, Molloy PL and Graham LD: CRNDE: A long non-coding RNA involved in cancer, neurobiology, and development. Front Genet. 3:2702012. View Article : Google Scholar : PubMed/NCBI
25	He D, Gu X, Jiang L, Jin J and Ma X: A methylation-based regulatory network for microRNA 320a in chemoresistant breast cancer. Mol Pharmacol. 86:536–547. 2014. View Article : Google Scholar : PubMed/NCBI
26	He DX, Gu XT, Li YR, Jiang L, Jin J and Ma X: Methylation-regulated miRNA-149 modulates chemoresistance by targeting NDST1 in human breast cancer. FEBS J. 281:4718–4730. 2014. View Article : Google Scholar : PubMed/NCBI
27	Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, et al: Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 458:223–227. 2009. View Article : Google Scholar : PubMed/NCBI
28	Marone M, Scambia G, Giannitelli C, Ferrandina G, Masciullo V, Bellacosa A, Benedetti-Panici P and Mancuso S: Analysis of cyclin E and CDK2 in ovarian cancer: Gene amplification and RNA overexpression. Int J Cancer. 75:34–39. 1998. View Article : Google Scholar : PubMed/NCBI
29	Opyrchal M, Salisbury JL, Iankov I, Goetz MP, McCubrey J, Gambino MW, Malatino L, Puccia G, Ingle JN, Galanis E, et al: Inhibition of Cdk2 kinase activity selectively targets the CD44⁺/CD24⁺/Low stem-like subpopulation and restores chemosensitivity of SUM149PT triple-negative breast cancer cells. Int J Oncol. 45:1193–1199. 2014.PubMed/NCBI
30	Gerstein MB, Kundaje A, Hariharan M, Landt SG, Yan KK, Cheng C, Mu XJ, Khurana E, Rozowsky J, Alexander R, et al: Architecture of the human regulatory network derived from ENCODE data. Nature. 489:91–100. 2012. View Article : Google Scholar : PubMed/NCBI
31	Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
32	Iozzo RV and Sanderson RD: Proteoglycans in cancer biology, tumour microenvironment and angiogenesis. J Cell Mol Med. 15:1013–1031. 2011. View Article : Google Scholar
33	Rakoff-Nahoum S and Medzhitov R: Toll-like receptors and cancer. Nat Rev Cancer. 9:57–63. 2009. View Article : Google Scholar
34	Fu D and Roufogalis BD: Actin disruption inhibits endosomal traffic of P-glycoprotein-EGFP and resistance to daunorubicin accumulation. Am J Physiol Cell Physiol. 292:C1543–C1552. 2007. View Article : Google Scholar
35	Gottesman MM: Mechanisms of cancer drug resistance. Annu Rev Med. 53:615–627. 2002. View Article : Google Scholar : PubMed/NCBI
36	Guil S and Esteller M: Cis-acting noncoding RNAs: Friends and foes. Nat Struct Mol Biol. 19:1068–1075. 2012. View Article : Google Scholar : PubMed/NCBI
37	Townsend DM and Tew KD: The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene. 22:7369–7375. 2003. View Article : Google Scholar : PubMed/NCBI
38	Traverso N, Ricciarelli R, Nitti M, Marengo B, Furfaro AL, Pronzato MA, Marinari UM and Domenicotti C: Role of glutathione in cancer progression and chemoresistance. Oxid Med Cell Longev. 2013:9729132013. View Article : Google Scholar : PubMed/NCBI
39	Yu J, Zhang Y, Qi Z, Kurtycz D, Vacano G and Patterson D: Methylation-mediated downregulation of the B-cell translocation gene 3 (BTG3) in breast cancer cells. Gene Expr. 14:173–182. 2008.PubMed/NCBI
40	Ru P, Steele R, Hsueh EC and Ray RB: Anti-miR-203 upregulates SOCS3 expression in breast cancer cells and enhances cisplatin chemosensitivity. Genes Cancer. 2:720–727. 2011. View Article : Google Scholar : PubMed/NCBI
41	Wang W and Figg WD: Secondary BRCA1 and BRCA2 alterations and acquired chemoresistance. Cancer Biol Ther. 7:1004–1005. 2008. View Article : Google Scholar : PubMed/NCBI
42	Seth A and Watson DK: ETS transcription factors and their emerging roles in human cancer. Eur J Cancer. 41:2462–2478. 2005. View Article : Google Scholar : PubMed/NCBI
43	Huang X, Brown C, Ni W, Maynard E, Rigby AC and Oettgen P: Critical role for the Ets transcription factor ELF-1 in the development of tumor angiogenesis. Blood. 107:3153–3160. 2006. View Article : Google Scholar
44	Li Z, Chao TC, Chang KY, Lin N, Patil VS, Shimizu C, Head SR, Burns JC and Rana TM: The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL. Proc Natl Acad Sci USA. 111:1002–1007. 2014. View Article : Google Scholar
45	Lee JM, Dedhar S, Kalluri R and Thompson EW: The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol. 172:973–981. 2006. View Article : Google Scholar : PubMed/NCBI
46	Pieraccioli M, Imbastari F, Antonov A, Melino G and Raschellà G: Activation of miR200 by c-Myb depends on ZEB1 expression and miR200 promoter methylation. Cell Cycle. 12:2309–2320. 2013. View Article : Google Scholar : PubMed/NCBI
47	Han HB, Gu J, Zuo HJ, Chen ZG, Zhao W, Li M, Ji DB, Lu YY and Zhang ZQ: Let-7c functions as a metastasis suppressor by targeting MMP11 and PBX3 in colorectal cancer. J Pathol. 226:544–555. 2012. View Article : Google Scholar
48	Knoll S, Emmrich S and Pützer BM: The E2F1-miRNA cancer progression network. Adv Exp Med Biol. 774:135–147. 2013. View Article : Google Scholar : PubMed/NCBI
49	Frietze S, Lupien M, Silver PA and Brown M: CARM1 regulates estrogen-stimulated breast cancer growth through up-regulation of E2F1. Cancer Res. 68:301–306. 2008. View Article : Google Scholar : PubMed/NCBI
50	Louie MC, Zou JX, Rabinovich A and Chen HW: ACTR/AIB1 functions as an E2F1 coactivator to promote breast cancer cell proliferation and antiestrogen resistance. Mol Cell Biol. 24:5157–5171. 2004. View Article : Google Scholar : PubMed/NCBI