Functions of lncRNA HOTAIR in lung cancer

Journal of Hematology & Oncology

Bin Shan¹  Ying Zhuo³  Janarthanan Jayawickramarajah²  Gregory Loewen⁴ 

[1] College of Medical Sciences, Washington State University Spokane, 412 E. Spokane Falls Boulevard, Spokane 99202, WA, USA;Department of Chemistry, Tulane University, 2015 Percival Stern Hall, New Orleans 70118, LA, USA;Kadlec Regional Medical Center, 888 Swift Boulevard, Richland 99352, WA, USA;Providence Regional Cancer Center, 105 W. 8th Avenue, Spokane 99204, WA, USA

关键词: Metastasis;    PRC2;    Lung cancer;    HOTAIR;    lncRNA;   

Others  :  1137551
DOI  :  10.1186/s13045-014-0090-4

 received in 2014-10-01, accepted in 2014-11-22,  发布年份 2014

【 摘 要 】

Long non-coding RNAs (lncRNAs) govern fundamental biochemical and cellular processes. lncRNA HOX transcript antisense RNA (HOTAIR) represses gene expression through recruitment of chromatin modifiers. The expression of HOTAIR is elevated in lung cancer and correlates with metastasis and poor prognosis. Moreover, HOTAIR promotes proliferation, survival, invasion, metastasis, and drug resistance in lung cancer cells. Here we review the molecular mechanisms underlying HOTAIR-mediated aggressive phenotypes of lung cancer. We also discuss HOTAIR’s potential in diagnosis and treatment of lung cancer, as well as the challenges of exploiting HOTAIR for intervention of lung cancer.

【 授权许可】

   
2014 Loewen et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue C, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Roder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Bar NS, Batut P, Bell K, Bell I, Chakrabortty S, Chen X, Chrast J, Curado J, et al.: Landscape of transcription in human cells. Nature 2012, 489(7414):101-108.
• [2]Rinn JL, Chang HY: Genome regulation by long noncoding RNAs. Annu Rev Biochem 2012, 81:145-166.
• [3]Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan X, Ruan Y, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigo R: The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 2012, 22(9):1775-1789.
• [4]Wang KC, Chang HY: Molecular mechanisms of long noncoding RNAs. Mol Cell 2011, 43(6):904-914.
• [5]Booton R, Lindsay MA: Emerging role of MicroRNAs and long noncoding RNAs in respiratory disease. Chest 2014, 146(1):193-204.
• [6]Zhang H, Chen Z, Wang X, Huang Z, He Z, Chen Y: Long non-coding RNA: a new player in cancer. J Hematol Oncol 2013, 6:37.
• [7]Prensner JR, Chinnaiyan AM: The emergence of lncRNAs in cancer biology. Canc Discov 2011, 1(5):391-407.
• [8]White NM, Cabanski CR, Silva-Fisher JM, Dang HX, Govindan R, Maher CA: Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer. Genome Biol 2014, 15(8):429.
• [9]Yang J, Lin J, Liu T, Chen T, Pan S, Huang W, Li S: Analysis of lncRNA expression profiles in non-small cell lung cancers (NSCLC) and their clinical subtypes. Lung Cancer 2014, 85(2):110-115.
• [10]Xu G, Chen J, Pan Q, Huang K, Pan J, Zhang W, Chen J, Yu F, Zhou T, Wang Y: Long noncoding RNA expression profiles of lung adenocarcinoma ascertained by microarray analysis. PLoS One 2014, 9(8):e104044.
• [11]Wang Y, Chen W, Chen J, Pan Q, Pan J: LncRNA expression profiles of EGFR exon 19 deletions in lung adenocarcinoma ascertained by using microarray analysis. Med Oncol 2014, 31(9):137.
• [12]Yang Y, Li H, Hou S, Hu B, Liu J, Wang J: The noncoding RNA expression profile and the effect of lncRNA AK126698 on cisplatin resistance in non-small-cell lung cancer cell. PLoS One 2013, 8(5):e65309.
• [13]Luo J, Tang L, Zhang J, Ni J, Zhang HP, Zhang L, Xu JF, Zheng D: Long non-coding RNA CARLo-5 is a negative prognostic factor and exhibits tumor pro-oncogenic activity in non-small cell lung cancer. Tumour Biol 2014, 35(11):11541-11549.
• [14]Qiu M, Xu Y, Yang X, Wang J, Hu J, Xu L, Yin R: CCAT2 is a lung adenocarcinoma-specific long non-coding RNA and promotes invasion of non-small cell lung cancer. Tumour Biol 2014, 35(6):5375-5380.
• [15]Liu F, Killian JK, Yang M, Walker RL, Hong JA, Zhang M, Davis S, Zhang Y, Hussain M, Xi S, Rao M, Meltzer PA, Schrump DS: Epigenomic alterations and gene expression profiles in respiratory epithelia exposed to cigarette smoke condensate. Oncogene 2010, 29(25):3650-3664.
• [16]Kaplan R, Luettich K, Heguy A, Hackett NR, Harvey BG, Crystal RG: Monoallelic up-regulation of the imprinted H19 gene in airway epithelium of phenotypically normal cigarette smokers. Cancer Res 2003, 63(7):1475-1482.
• [17]Kondo M, Suzuki H, Ueda R, Osada H, Takagi K, Takahashi T, Takahashi T: Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. Oncogene 1995, 10(6):1193-1198.
• [18]Chen B, Yu M, Chang Q, Lu Y, Thakur C, Ma D, Yi Z, Chen F: Mdig de-represses H19 large intergenic non-coding RNA (lincRNA) by down-regulating H3K9me3 and heterochromatin. Oncotarget 2013, 4(9):1427-1437.
• [19]Zhuang Y, Wang X, Nguyen HT, Zhuo Y, Cui X, Fewell C, Flemington EK, Shan B: Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen. J Hematol Oncol 2013, 6:35.
• [20]Zhao W, An Y, Liang Y, Xie XW: Role of HOTAIR long noncoding RNA in metastatic progression of lung cancer. Eur Rev Med Pharmacol Sci 2014, 18(13):1930-1936.
• [21]Ono H, Motoi N, Nagano H, Miyauchi E, Ushijima M, Matsuura M, Okumura S, Nishio M, Hirose T, Inase N, Ishikawa Y: Long noncoding RNA HOTAIR is relevant to cellular proliferation, invasiveness, and clinical relapse in small-cell lung cancer. Cancer Med 2014, 3(3):632-642.
• [22]Liu Z, Sun M, Lu K, Liu J, Zhang M, Wu W, De W, Wang Z, Wang R: The long noncoding RNA HOTAIR contributes to cisplatin resistance of human lung adenocarcinoma cells via downregualtion of p21(WAF1/CIP1) expression. PLoS One 2013, 8(10):e77293.
• [23]Liu XH, Liu ZL, Sun M, Liu J, Wang ZX, De W: The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer. BMC Cancer 2013, 13:464.
• [24]Nakagawa T, Endo H, Yokoyama M, Abe J, Tamai K, Tanaka N, Sato I, Takahashi S, Kondo T, Satoh K: Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer. Biochem Biophys Res Commun 2013, 436(2):319-324.
• [25]Schmidt LH, Gorlich D, Spieker T, Rohde C, Schuler M, Mohr M, Humberg J, Sauer T, Thoenissen NH, Huge A, Voss R, Marra A, Faldum A, Muller-Tidow C, Berdel WE, Wiewrodt R: Prognostic impact of Bcl-2 depends on tumor histology and expression of MALAT-1 lncRNA in Non-small-cell lung cancer. J Thorac Oncol 2014, 9(9):1294-1304.
• [26]Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, Hung G, Revenko A, Arun G, Stentrup M, Gross M, Zornig M, MacLeod AR, Spector DL, Diederichs S: The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 2013, 73(3):1180-1189.
• [27]Shen L, Chen L, Wang Y, Jiang X, Xia H, Zhuang Z: Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer.J Neuro-Oncol 2014. [Epub ahead of print]
• [28]Weber DG, Johnen G, Casjens S, Bryk O, Pesch B, Jockel KH, Kollmeier J, Bruning T: Evaluation of long noncoding RNA MALAT1 as a candidate blood-based biomarker for the diagnosis of non-small cell lung cancer. BMC Res Notes 2013, 6:518.
• [29]Nie FQ, Zhu Q, Xu TP, Zou YF, Xie M, Sun M, Xia R, Lu KH: Long non-coding RNA MVIH indicates a poor prognosis for non-small cell lung cancer and promotes cell proliferation and invasion. Tumour Biol 2014, 35(8):7587-7594.
• [30]Thai P, Statt S, Chen CH, Liang E, Campbell C, Wu R: Characterization of a novel long noncoding RNA, SCAL1, induced by cigarette smoke and elevated in lung cancer cell lines. Am J Respir Cell Mol Biol 2013, 49(2):204-211.
• [31]Hou Z, Zhao W, Zhou J, Shen L, Zhan P, Xu C, Chang C, Bi H, Zou J, Yao X, Huang R, Yu L, Yan J: A long noncoding RNA Sox2ot regulates lung cancer cell proliferation and is a prognostic indicator of poor survival. Int J Biochem Cell Biol 2014, 53:380-388.
• [32]Zhang L, Zhou XF, Pan GF, Zhao JP: Enhanced expression of long non-coding RNA ZXF1 promoted the invasion and metastasis in lung adenocarcinoma. Biomed Pharmacother 2014, 68(4):401-407.
• [33]Sun M, Liu XH, Wang KM, Nie FQ, Kong R, Yang JS, Xia R, Xu TP, Jin FY, Liu ZJ, Chen JF, Zhang EB, De W, Wang ZX: 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. Mol Cancer 2014, 13:68.
• [34]Han L, Kong R, Yin DD, Zhang EB, Xu TP, De W, Shu YQ: Low expression of long noncoding RNA GAS6-AS1 predicts a poor prognosis in patients with NSCLC. Med Oncol 2013, 30(4):694.
• [35]Lu KH, Li W, Liu XH, Sun M, Zhang ML, Wu WQ, Xie WP, Hou YY: Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer 2013, 13:461.
• [36]Sun M, Liu XH, Lu KH, Nie FQ, Xia R, Kong R, Yang JS, Xu TP, Liu YW, Zou YF, Lu BB, Yin R, Zhang EB, Xu L, De W, Wang ZX: EZH2-mediated epigenetic suppression of long noncoding RNA SPRY4-IT1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition. Cell Death Dis 2014, 5:e1298.
• [37]Arab K, Park YJ, Lindroth AM, Schafer A, Oakes C, Weichenhan D, Lukanova A, Lundin E, Risch A, Meister M, Dienemann H, Dyckhoff G, Herold-Mende C, Grummt I, Niehrs C, Plass C: Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A. Mol Cell 2014, 55(4):604-614.
• [38]Zhang EB, Yin DD, Sun M, Kong R, Liu XH, You LH, Han L, Xia R, Wang KM, Yang JS, De W, Shu YQ, Wang ZX: P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell Death Dis 2014, 5:e1243.
• [39]Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY: Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 2007, 129(7):1311-1323.
• [40]Wu L, Murat P, Matak-Vinkovic D, Murrell A, Balasubramanian S: Binding interactions between long noncoding RNA HOTAIR and PRC2 proteins. Biochemistry 2013, 52(52):9519-9527.
• [41]Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY: Long noncoding RNA as modular scaffold of histone modification complexes. Science 2010, 329(5992):689-693.
• [42]Kirmizis A, Bartley SM, Kuzmichev A, Margueron R, Reinberg D, Green R, Farnham PJ: Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27. Genes Dev 2004, 18(13):1592-1605.
• [43]Chu C, Qu K, Zhong FL, Artandi SE, Chang HY: Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol Cell 2011, 44(4):667-678.
• [44]Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y: Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 2004, 119(7):941-953.
• [45]Amort T, Souliere MF, Wille A, Jia XY, Fiegl H, Worle H, Micura R, Lusser A: Long non-coding RNAs as targets for cytosine methylation. RNA Biol 2013, 10(6):1003-1008.
• [46]Li L, Liu B, Wapinski OL, Tsai MC, Qu K, Zhang J, Carlson JC, Lin M, Fang F, Gupta RA, Helms JA, Chang HY: Targeted disruption of Hotair leads to homeotic transformation and gene derepression. Cell Rep 2013, 5(1):3-12.
• [47]Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D: The human genome browser at UCSC. Genome Res 2002, 12(6):996-1006.
• [48]Mercer TR, Gerhardt DJ, Dinger ME, Crawford J, Trapnell C, Jeddeloh JA, Mattick JS, Rinn JL: Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nat Biotechnol 2012, 30(1):99-104.
• [49]Padua Alves C, Fonseca AS, Muys BR, de Barros ELBR, Burger MC, de Souza JE, Valente V, Zago MA, Silva WA Jr: Brief report: the lincRNA hotair is required for epithelial-to-mesenchymal transition and stemness maintenance of cancer cell lines. Stem Cells 2013, 31(12):2827-2832.
• [50]Bhan A, Hussain I, Ansari KI, Kasiri S, Bashyal A, Mandal SS: Antisense transcript long noncoding RNA (lncRNA) HOTAIR is transcriptionally induced by estradiol. J Mol Biol 2013, 425(19):3707-3722.
• [51]Chen FJ, Sun M, Li SQ, Wu QQ, Ji L, Liu ZL, Zhou GZ, Cao G, Jin L, Xie HW, Wang CM, Lv J, De W, Wu M, Cao XF: Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis. Mol Carcinog 2013, 52(11):908-915.
• [52]Chisholm KM, Wan Y, Li R, Montgomery KD, Chang HY, West RB: Detection of long non-coding RNA in archival tissue: correlation with polycomb protein expression in primary and metastatic breast carcinoma. PLoS One 2012, 7(10):e47998.
• [53]Chiyomaru T, Fukuhara S, Saini S, Majid S, Deng G, Shahryari V, Chang I, Tanaka Y, Enokida H, Nakagawa M, Dahiya R, Yamamura S: Long non-coding RNA HOTAIR is targeted and regulated by miR-141 in human cancer cells. J Biol Chem 2014, 289(18):12550-12565.
• [54]Chiyomaru T, Yamamura S, Fukuhara S, Yoshino H, Kinoshita T, Majid S, Saini S, Chang I, Tanaka Y, Enokida H, Seki N, Nakagawa M, Dahiya R: Genistein inhibits prostate cancer cell growth by targeting miR-34a and oncogenic HOTAIR. PLoS One 2013, 8(8):e70372.
• [55]Cuenda A, Rouse J, Doza YN, Meier R, Cohen P, Gallagher TF, Young PR, Lee JC: SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett 1995, 364(2):229-233.
• [56]Cui L, Xie XY, Wang H, Chen XL, Liu SL, Hu LN: [Expression of long non-coding RNA HOTAIR mRNA in ovarian cancer]. Sichuan Da Xue Xue Bao Yi Xue Ban 2013, 44(1):57-59.
• [57]Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H, Fujiya T, Sato I, Yamaguchi K, Tanaka N, Iijima K, Shimosegawa T, Sugamura K, Satoh K: Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. PLoS One 2013, 8(10):e77070.
• [58]Ge XS, Ma HJ, Zheng XH, Ruan HL, Liao XY, Xue WQ, Chen YB, Zhang Y, Jia WH: HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway. Cancer Sci 2013, 104(12):1675-1682.
• [59]Geng YJ, Xie SL, Li Q, Ma J, Wang GY: Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res 2011, 39(6):2119-2128.
• [60]Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY: Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 2010, 464(7291):1071-1076.
• [61]Hajjari M, Behmanesh M, Sadeghizadeh M, Zeinoddini M: Up-regulation of HOTAIR long non-coding RNA in human gastric adenocarcinoma tissues. Med Oncol 2013, 30(3):670.
• [62]Ishibashi M, Kogo R, Shibata K, Sawada G, Takahashi Y, Kurashige J, Akiyoshi S, Sasaki S, Iwaya T, Sudo T, Sugimachi K, Mimori K, Wakabayashi G, Mori M: Clinical significance of the expression of long non-coding RNA HOTAIR in primary hepatocellular carcinoma. Oncol Rep 2013, 29(3):946-950.
• [63]Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, Kim S, Safe S: HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene 2013, 32(13):1616-1625.
• [64]Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, Tanaka F, Shibata K, Suzuki A, Komune S, Miyano S, Mori M: Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res 2011, 71(20):6320-6326.
• [65]Li D, Feng J, Wu T, Wang Y, Sun Y, Ren J, Liu M: Long intergenic noncoding RNA HOTAIR is overexpressed and regulates PTEN methylation in laryngeal squamous cell carcinoma. Am J Pathol 2013, 182(1):64-70.
• [66]Li G, Zhang H, Wan X, Yang X, Zhu C, Wang A, He L, Miao R, Chen S, Zhao H: Long noncoding RNA plays a key role in metastasis and prognosis of hepatocellular carcinoma. Biomed Res Int 2014, 2014:780521.
• [67]Li Z, Li C, Liu C, Yu S, Zhang Y: Expression of the long non-coding RNAs MEG3, HOTAIR, and MALAT-1 in non-functioning pituitary adenomas and their relationship to tumor behavior.Pituitary 2014. [Epub ahead of print]
• [68]Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, Kong R, Xia R, Lu KH, Li JH, De W, Wang KM, Wang ZX: Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer 2014, 13:92.
• [69]Lu L, Zhu G, Zhang C, Deng Q, Katsaros D, Mayne ST, Risch HA, Mu L, Canuto EM, Gregori G, Benedetto C, Yu H: Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer. Breast Cancer Res Treat 2012, 136(3):875-883.
• [70]Lv XB, Lian GY, Wang HR, Song E, Yao H, Wang MH: Long noncoding RNA HOTAIR is a prognostic marker for esophageal squamous cell carcinoma progression and survival. PLoS One 2013, 8(5):e63516.
• [71]Milhem MM, Knutson T, Yang S, Zhu D, Wang X, Leslie KK, Meng X: Correlation of MTDH/AEG-1 and HOTAIR expression with metastasis and response to treatment in sarcoma patients. J Canc Sci Ther 2011, S5(4):pii:004.
• [72]Nie Y, Liu X, Qu S, Song E, Zou H, Gong C: Long non-coding RNA HOTAIR is an independent prognostic marker for nasopharyngeal carcinoma progression and survival. Cancer Sci 2013, 104(4):458-464.
• [73]Niinuma T, Suzuki H, Nojima M, Nosho K, Yamamoto H, Takamaru H, Yamamoto E, Maruyama R, Nobuoka T, Miyazaki Y, Nishida T, Bamba T, Kanda T, Ajioka Y, Taguchi T, Okahara S, Takahashi H, Nishida Y, Hosokawa M, Hasegawa T, Tokino T, Hirata K, Imai K, Toyota M, Shinomura Y: Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. Cancer Res 2012, 72(5):1126-1136.
• [74]Ozgur E, Mert U, Isin M, Okutan M, Dalay N, Gezer U: Differential expression of long non-coding RNAs during genotoxic stress-induced apoptosis in HeLa and MCF-7 cells. Clin Exp Med 2013, 13(2):119-126.
• [75]Schiavo G, D’Anto V, Cantile M, Procino A, Di Giovanni S, Valletta R, Terracciano L, Baumhoer D, Jundt G, Cillo C: Deregulated HOX genes in ameloblastomas are located in physical contiguity to keratin genes. J Cell Biochem 2011, 112(11):3206-3215.
• [76]Tang L, Zhang W, Su B, Yu B: Long noncoding RNA HOTAIR is associated with motility, invasion, and metastatic potential of metastatic melanoma. Biomed Res Int 2013, 2013:251098.
• [77]Wang J, Zhou Y, Lu J, Sun Y, Xiao H, Liu M, Tian L: Combined detection of serum exosomal miR-21 and HOTAIR as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma. Med Oncol 2014, 31(9):148.
• [78]Wang L, Zeng X, Chen S, Ding L, Zhong J, Zhao JC, Wang L, Sarver A, Koller A, Zhi J, Ma Y, Yu J, Chen J, Huang H: BRCA1 is a negative modulator of the PRC2 complex. EMBO J 2013, 32(11):1584-1597.
• [79]Xu ZY, Yu QM, Du YA, Yang LT, Dong RZ, Huang L, Yu PF, Cheng XD: Knockdown of long non-coding RNA HOTAIR suppresses tumor invasion and reverses epithelial-mesenchymal transition in gastric cancer. Int J Biol Sci 2013, 9(6):587-597.
• [80]Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F, Zheng SS: Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol 2011, 18(5):1243-1250.
• [81]Zhang JX, Han L, Bao ZS, Wang YY, Chen LY, Yan W, Yu SZ, Pu PY, Liu N, You YP, Jiang T, Kang CS: HOTAIR, a cell cycle-associated long noncoding RNA and a strong predictor of survival, is preferentially expressed in classical and mesenchymal glioma. Neuro-Oncology 2013, 15(12):1595-1603.
• [82]Loewen G, Zhuo Y, Zhuang Y, Jayawickramarajah J, Shan B: lincRNA HOTAIR as a novel promoter of cancer progression. J Canc Res Updates 2014, 3(3):7.
• [83]Gutierrez SE, Romero-Oliva FA: Epigenetic changes: a common theme in acute myelogenous leukemogenesis. J Hematol Oncol 2013, 6:57.
• [84]Zhang X, Zhou L, Fu G, Sun F, Shi J, Wei J, Lu C, Zhou C, Yuan Q, Yang M: The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic enhancer. Carcinogenesis 2014, 35(9):2062-2067.
• [85]Ma MZ, Li CX, Zhang Y, Weng MZ, Zhang MD, Qin YY, Gong W, Quan ZW: Long non-coding RNA HOTAIR, a c-Myc activated driver of malignancy, negatively regulates miRNA-130a in gallbladder cancer. Mol Cancer 2014, 13:156.
• [86]Zajac-Kaye M: Myc oncogene: a key component in cell cycle regulation and its implication for lung cancer. Lung Cancer 2001, 34(Suppl 2):S43-S46.
• [87]Li LC, Dahiya R: MethPrimer: designing primers for methylation PCRs. Bioinformatics 2002, 18(11):1427-1431.
• [88]Yoon JH, Abdelmohsen K, Gorospe M: Functional interactions among microRNAs and long noncoding RNAs. Semin Cell Dev Biol 2014, 34C:9-14.
• [89]Brabletz S, Brabletz T: The ZEB/miR-200 feedback loop–a motor of cellular plasticity in development and cancer? EMBO Rep 2010, 11(9):670-677.
• [90]Yoon JH, Abdelmohsen K, Kim J, Yang X, Martindale JL, Tominaga-Yamanaka K, White EJ, Orjalo AV, Rinn JL, Kreft SG, Wilson GM, Gorospe M: Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination. Nat Commun 2013, 4:2939.
• [91]Osada H, Takahashi T: let-7 and miR-17-92: small-sized major players in lung cancer development. Cancer Sci 2011, 102(1):9-17.
• [92]Kasinski AL, Slack FJ: miRNA-34 prevents cancer initiation and progression in a therapeutically resistant K-ras and p53-induced mouse model of lung adenocarcinoma. Cancer Res 2012, 72(21):5576-5587.
• [93]Gallardo E, Navarro A, Vinolas N, Marrades RM, Diaz T, Gel B, Quera A, Bandres E, Garcia-Foncillas J, Ramirez J, Monzo M: miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer. Carcinogenesis 2009, 30(11):1903-1909.
• [94]Baffa R, Fassan M, Volinia S, O’Hara B, Liu CG, Palazzo JP, Gardiman M, Rugge M, Gomella LG, Croce CM, Rosenberg A: MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol 2009, 219(2):214-221.
• [95]Shan B, Yao TP, Nguyen HT, Zhuo Y, Levy DR, Klingsberg RC, Tao H, Palmer ML, Holder KN, Lasky JA: Requirement of HDAC6 for transforming growth factor-beta1-induced epithelial-mesenchymal transition. J Biol Chem 2008, 283(30):21065-21073.
• [96]Antoon JW, Lai R, Struckhoff AP, Nitschke AM, Elliott S, Martin EC, Rhodes LV, Yoon NS, Salvo VA, Shan B, Beckman BS, Nephew KP, Burow ME: Altered death receptor signaling promotes epithelial-to-mesenchymal transition and acquired chemoresistance. Sci Rep 2012, 2:539.
• [97]Zhou C, Nitschke AM, Xiong W, Zhang Q, Tang Y, Bloch M, Elliott S, Zhu Y, Bazzone L, Yu D, Weldon CB, Schiff R, McLachlan JA, Beckman BS, Wiese TE, Nephew KP, Shan B, Burow ME, Wang G: Proteomic analysis of tumor necrosis factor-alpha resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype. Breast Cancer Res 2008, 10(6):R105.
• [98]Zhuang Y, Nguyen HT, Burow ME, Zhuo Y, El-Dahr SS, Yao X, Cao S, Flemington EK, Nephew KP, Fang F, Collins-Burow B, Rhodes LV, Yu Q, Jayawickramarajah J, Shan B: Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells.Mol Carcinog 2014. [Epub ahead of print]
• [99]Li C, Nguyen HT, Zhuang Y, Lin Y, Flemington EK, Guo W, Guenther J, Burow ME, Morris GF, Sullivan D, Shan B: Post-transcriptional up-regulation of miR-21 by type I collagen. Mol Carcinog 2011, 50(7):563-570.
• [100]Li C, Nguyen HT, Zhuang Y, Lin Z, Flemington EK, Zhuo Y, Kantrow SP, Morris GF, Sullivan DE, Shan B: Comparative profiling of miRNA expression of lung adenocarcinoma cells in two-dimensional and three-dimensional cultures. Gene 2012, 511(2):143-150.
• [101]Nguyen HT, Li C, Lin Z, Zhuang Y, Flemington EK, Burow ME, Lin Y, Shan B: The microRNA expression associated with morphogenesis of breast cancer cells in three-dimensional organotypic culture. Oncol Rep 2012, 28(1):117-126.
• [102]Nguyen HT, Zhuang Y, Sun L, Kantrow SP, Kolls JK, You Z, Zhuo Y, Shan B: Src-mediated morphology transition of lung cancer cells in three-dimensional organotypic culture. Cancer Cell Int 2013, 13(1):16.
• [103]Mandeville I, Aubin J, LeBlanc M, Lalancette-Hebert M, Janelle MF, Tremblay GM, Jeannotte L: Impact of the loss of Hoxa5 function on lung alveogenesis. Am J Pathol 2006, 169(4):1312-1327.
• [104]Liu XH, Lu KH, Wang KM, Sun M, Zhang EB, Yang JS, Yin DD, Liu ZL, Zhou J, Liu ZJ, De W, Wang ZX: MicroRNA-196a promotes non-small cell lung cancer cell proliferation and invasion through targeting HOXA5. BMC Cancer 2012, 12:348.
• [105]Thiery JP, Acloque H, Huang RY, Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell 2009, 139(5):871-890.
• [106]Shan B, Zhuo Y, Chin D, Morris CA, Morris GF, Lasky JA: Cyclin-dependent kinase 9 is required for tumor necrosis factor-alpha-stimulated matrix metalloproteinase-9 expression in human lung adenocarcinoma cells. J Biol Chem 2005, 280(2):1103-1111.
• [107]Coe BP, Thu KL, Aviel-Ronen S, Vucic EA, Gazdar AF, Lam S, Tsao MS, Lam WL: Genomic deregulation of the E2F/Rb pathway leads to activation of the oncogene EZH2 in small cell lung cancer. PLoS One 2013, 8(8):e71670.
• [108]Liu C, Shi X, Wang L, Wu Y, Jin F, Bai C, Song Y: SUZ12 is involved in progression of non-small cell lung cancer by promoting cell proliferation and metastasis. Tumour Biol 2014, 35(6):6073-6082.
• [109]Hayami S, Kelly JD, Cho HS, Yoshimatsu M, Unoki M, Tsunoda T, Field HI, Neal DE, Yamaue H, Ponder BA, Nakamura Y, Hamamoto R: Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int J Cancer 2011, 128(3):574-586.
• [110]Lv T, Yuan D, Miao X, Lv Y, Zhan P, Shen X, Song Y: Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer. PLoS One 2012, 7(4):e35065.
• [111]Sekido Y, Fong KM, Minna JD: Molecular genetics of lung cancer. Annu Rev Med 2003, 54:73-87.
• [112]Lee Y, Fryer JD, Kang H, Crespo-Barreto J, Bowman AB, Gao Y, Kahle JJ, Hong JS, Kheradmand F, Orr HT, Finegold MJ, Zoghbi HY: ATXN1 protein family and CIC regulate extracellular matrix remodeling and lung alveolarization. Dev Cell 2011, 21(4):746-757.
• [113]Li X, Shi Y, Yin Z, Xue X, Zhou B: An eight-miRNA signature as a potential biomarker for predicting survival in lung adenocarcinoma. J Transl Med 2014, 12:159.
• [114]Acunzo M, Visone R, Romano G, Veronese A, Lovat F, Palmieri D, Bottoni A, Garofalo M, Gasparini P, Condorelli G, Chiariello M, Croce CM: miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222. Oncogene 2012, 31(5):634-642.
• [115]Arita T, Ichikawa D, Konishi H, Komatsu S, Shiozaki A, Shoda K, Kawaguchi T, Hirajima S, Nagata H, Kubota T, Fujiwara H, Okamoto K, Otsuji E: Circulating long non-coding RNAs in plasma of patients with gastric cancer. Anticancer Res 2013, 33(8):3185-3193.
• [116]Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 2006, 103(7):2257-2261.
• [117]Kikuchi J, Takashina T, Kinoshita I, Kikuchi E, Shimizu Y, Sakakibara-Konishi J, Oizumi S, Marquez VE, Nishimura M, Dosaka-Akita H: Epigenetic therapy with 3-deazaneplanocin A, an inhibitor of the histone methyltransferase EZH2, inhibits growth of non-small cell lung cancer cells. Lung Cancer 2012, 78(2):138-143.
• [118]Sato T, Kaneda A, Tsuji S, Isagawa T, Yamamoto S, Fujita T, Yamanaka R, Tanaka Y, Nukiwa T, Marquez VE, Ishikawa Y, Ichinose M, Aburatani H: PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer. Sci Rep 2013, 3:1911.
• [119]Zhao J, Ohsumi TK, Kung JT, Ogawa Y, Grau DJ, Sarma K, Song JJ, Kingston RE, Borowsky M, Lee JT: Genome-wide identification of polycomb-associated RNAs by RIP-seq. Mol Cell 2010, 40(6):939-953.
• [120]Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, Regev A, Lander ES, Rinn JL: Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 2009, 106(28):11667-11672.
• [121]Lee ST, Li Z, Wu Z, Aau M, Guan P, Karuturi RK, Liou YC, Yu Q: Context-specific regulation of NF-kappaB target gene expression by EZH2 in breast cancers. Mol Cell 2011, 43(5):798-810.
• [122]He A, Shen X, Ma Q, Cao J, von Gise A, Zhou P, Wang G, Marquez VE, Orkin SH, Pu WT: PRC2 directly methylates GATA4 and represses its transcriptional activity. Genes Dev 2012, 26(1):37-42.