Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Review

HOTAIR: a key regulator in gynecologic cancers

Authors: Jing Li, Jing Wang, Yan Zhong, Ruixia Guo, Danxia Chu, Haifeng Qiu, Zhongfu Yuan

Published in: Cancer Cell International | Issue 1/2017

Login to get access

Abstract

Long non-coding RNAs (lncRNAs) play critical roles in the initiation and progression of human cancers. HOX transcript antisense RNA (HOTAIR) is an lncRNA localized to the mammalian HOXC gene cluster; it can interact with polycomb repressive complex 2 and the lysine-specific histone demethylase/CoREST/REST complex, and it manipulates the expression of various genes. HOTAIR promotes tumor invasion and metastasis by silencing tumor suppressors, and activating oncogenes and signaling pathways. HOTAIR is deregulated in many human cancers; despite its critical roles in health and disease, the underlying mechanisms governing HOTAIR function are unknown. In this review, we summarize the recent findings on the roles of HOTAIR in gynecologic cancers.
Literature
1.
Bertone P, Stolc V, Royce TE, Rozowsky JS, Urban AE, Zhu X, Rinn JL, Tongprasit W, Samanta M, Weissman S, et al. Global identification of human transcribed sequences with genome tiling arrays. Science. 2004;306(5705):2242–6.CrossRefPubMed
2.
Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, et al. The transcriptional landscape of the mammalian genome. Science. 2005;309(5740):1559–63.CrossRefPubMed
3.
Chen LL, Carmichael GG. Long noncoding RNAs in mammalian cells: what, where, and why? Wiley Interdiscipl Rev RNA. 2010;1(1):2–21.
4.
Lipovich L, Johnson R, Lin CY. MacroRNA underdogs in a microRNA world: evolutionary, regulatory, and biomedical significance of mammalian long non-protein-coding RNA. Biochim Biophys Acta. 2010;1799(9):597–615.CrossRefPubMed
5.
Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermuller J, Hofacker IL, et al. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science. 2007;316(5830):1484–8.CrossRefPubMed
6.
Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S, Nikaido I, Osato N, Saito R, Suzuki H, et al. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature. 2002;420(6915):563–73.CrossRefPubMed
7.
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. 2009;458(7235):223–7.CrossRefPubMedPubMedCentral
8.
Kapranov P, Drenkow J, Cheng J, Long J, Helt G, Dike S, Gingeras TR. Examples of the complex architecture of the human transcriptome revealed by RACE and high-density tiling arrays. Genome Res. 2005;15(7):987–97.CrossRefPubMedPubMedCentral
9.
Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 2012;22(9):1775–89.CrossRefPubMedPubMedCentral
10.
Hutchinson JN, Ensminger AW, Clemson CM, Lynch CR, Lawrence JB, Chess A. A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genom. 2007;8:39.CrossRef
11.
Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155–9.CrossRefPubMed
12.
Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 2007;129(7):1311–23.CrossRefPubMedPubMedCentral
13.
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):689–93.CrossRefPubMedPubMedCentral
14.
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. 2010;464(7291):1071–6.CrossRefPubMedPubMedCentral
15.
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.CrossRefPubMedPubMedCentral
16.
Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H, Fujiya T, Sato I, Yamaguchi K, Tanaka N, et al. Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. PLoS ONE. 2013;8(10):e77070.CrossRefPubMedPubMedCentral
17.
Chen FJ, Sun M, Li SQ, Wu QQ, Ji L, Liu ZL, Zhou GZ, Cao G, Jin L, Xie HW, et al. Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis. Mol Carcinog. 2013;52(11):908–15.CrossRefPubMed
18.
Ono H, Motoi N, Nagano H, Miyauchi E, Ushijima M, Matsuura M, Okumura S, Nishio M, Hirose T, Inase N, et al. Long noncoding RNA HOTAIR is relevant to cellular proliferation, invasiveness, and clinical relapse in small-cell lung cancer. Cancer Med. 2014;3(3):632–42.CrossRefPubMedPubMedCentral
19.
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.CrossRefPubMed
20.
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.CrossRefPubMedPubMedCentral
21.
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):587–97.CrossRefPubMedPubMedCentral
22.
Lee NK, Lee JH, Park CH, Yu D, Lee YC, Cheong JH, Noh SH, Lee SK. Long non-coding RNA HOTAIR promotes carcinogenesis and invasion of gastric adenocarcinoma. Biochem Biophys Res Commun. 2014;451(2):171–8.CrossRefPubMed
23.
Nakayama I, Shibazaki M, Yashima-Abo A, Miura F, Sugiyama T, Masuda T, Maesawa C. Loss of HOXD10 expression induced by upregulation of miR-10b accelerates the migration and invasion activities of ovarian cancer cells. Int J Oncol. 2013;43(1):63–71.PubMed
24.
Ding C, Cheng S, Yang Z, Lv Z, Xiao H, Du C, Peng C, Xie H, Zhou L, Wu J, et al. Long non-coding RNA HOTAIR promotes cell migration and invasion via down-regulation of RNA binding motif protein 38 in hepatocellular carcinoma cells. Int J Mol Sci. 2014;15(3):4060–76.CrossRefPubMedPubMedCentral
25.
Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, Kong R, Xia R, Lu KH, Li JH, et al. 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.CrossRefPubMedPubMedCentral
26.
Qiu JJ, Lin YY, Ye LC, Ding JX, Feng WW, Jin HY, Zhang Y, Li Q, Hua KQ. Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer. Gynecol Oncol. 2014;134(1):121–8.CrossRefPubMed
27.
Carrion K, Dyo J, Patel V, Sasik R, Mohamed SA, Hardiman G, Nigam V. The long non-coding HOTAIR is modulated by cyclic stretch and WNT/beta-CATENIN in human aortic valve cells and is a novel repressor of calcification genes. PLoS ONE. 2014;9(5):e96577.CrossRefPubMedPubMedCentral
28.
Yang G, Zhang S, Gao F, Liu Z, Lu M, Peng S, Zhang T, Zhang F. Osteopontin enhances the expression of HOTAIR in cancer cells via IRF1. Biochim Biophys Acta. 2014;1839(9):837–48.CrossRefPubMed
29.
Zhang H, Cai K, Wang J, Wang X, Cheng K, Shi F, Jiang L, Zhang Y, Dou J. MiR-7, inhibited indirectly by LincRNA HOTAIR, directly inhibits SETDB1 and reverses the EMT of breast cancer stem cells by downregulating the STAT3 pathway. Stem Cells. 2014;32:2858–68.CrossRefPubMed
30.
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.CrossRefPubMedPubMedCentral
31.
32.
Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, et al. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011;11(10):719–25.CrossRefPubMedPubMedCentral
33.
Bowtell DD, Bohm S, Ahmed AA, Aspuria PJ, Bast RC Jr, Beral V, Berek JS, Birrer MJ, Blagden S, Bookman MA, et al. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer. Nat Rev Cancer. 2015;15(11):668–79.CrossRefPubMedPubMedCentral
34.
Wu H, Shang X, Shi Y, Yang Z, Zhao J, Yang M, Li Y, Xu S. Genetic variants of lncRNA HOTAIR and risk of epithelial ovarian cancer among Chinese women. Oncotarget. 2016;7(27):41047–52.PubMedPubMedCentral
35.
Qiu H, Wang X, Guo R, Liu Q, Wang Y, Yuan Z, Li J, Shi H. HOTAIR rs920778 polymorphism is associated with ovarian cancer susceptibility and poor prognosis in a Chinese population. Future oncology. 2016.
36.
Cui L, Xie XY, Wang H, Chen XL, Liu SL, Hu LN. Expression of long non-coding RNA HOTAIR mRNA in ovarian cancer. J Sichuan Univ. 2013;44(1):57–9.
37.
Qiu JJ, Wang Y, Ding JX, Jin HY, Yang G, Hua KQ. The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis. Exp Cell Res. 2015;333(2):238–48.CrossRefPubMed
38.
Wang J, Chen D, He X, Zhang Y, Shi F, Wu D, Chen J, Zhang Y, Zhao F, Dou J. Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition. Cancer Cell Int. 2015;15:24.CrossRefPubMedPubMedCentral
39.
Xing CY, Hu XQ, Xie FY, Yu ZJ, Li HY, Bin Z, Wu JB, Tang LY, Gao SM. Long non-coding RNA HOTAIR modulates c-KIT expression through sponging miR-193a in acute myeloid leukemia. FEBS Lett. 2015;589(15):1981–7.CrossRefPubMed
40.
Zhang Z, Cheng J, Wu Y, Qiu J, Sun Y, Tong X. LncRNA HOTAIR controls the expression of Rab22a by sponging miR-373 in ovarian cancer. Mol Med Rep. 2016;14(3):2465–72.PubMedPubMedCentral
41.
Teschendorff AE, Lee SH, Jones A, Fiegl H, Kalwa M, Wagner W, Chindera K, Evans I, Dubeau L, Orjalo A, et al. HOTAIR and its surrogate DNA methylation signature indicate carboplatin resistance in ovarian cancer. Genome Med. 2015;7:108.CrossRefPubMedPubMedCentral
42.
Wang Y, Wang H, Song T, Zou Y, Jiang J, Fang L, Li P. HOTAIR is a potential target for the treatment of cisplatinresistant ovarian cancer. Mol Med Rep. 2015;12(2):2211–6.PubMed
43.
Yiwei T, Hua H, Hui G, Mao M, Xiang L. HOTAIR interacting with MAPK1 regulates ovarian cancer skov3 cell proliferation, migration, and invasion. Med Sci Monit Int Med J Exp Clin Res. 2015;21:1856–63.
44.
Dong L, Hui L. HOTAIR promotes proliferation, migration, and invasion of ovarian cancer SKOV3 cells through regulating PIK3R3. Med Sci Monit Int Med J Exp Clin Res. 2016;22:325–31.
45.
Ozes AR, Miller DF, Ozes ON, Fang F, Liu Y, Matei D, Huang T, Nephew KP. NF-kappaB-HOTAIR axis links DNA damage response, chemoresistance and cellular senescence in ovarian cancer. Oncogene. 2016;35(41):5350–61.CrossRefPubMedPubMedCentral
46.
Li J, Yang S, Su N, Wang Y, Yu J, Qiu H, He X. Overexpression of long non-coding RNA HOTAIR leads to chemoresistance by activating the Wnt/beta-catenin pathway in human ovarian cancer. Tumour Biol. 2015.
47.
48.
He X, Bao W, Li X, Chen Z, Che Q, Wang H, Wan XP. The long non-coding RNA HOTAIR is upregulated in endometrial carcinoma and correlates with poor prognosis. Int J Mol Med. 2014;33(2):325–32.PubMed
49.
Huang J, Ke P, Guo L, Wang W, Tan H, Liang Y, Yao S. Lentivirus-mediated RNA interference targeting the long noncoding RNA HOTAIR inhibits proliferation and invasion of endometrial carcinoma cells in vitro and in vivo. Int J Gynecol Cancer. 2014;24(4):635–42.CrossRefPubMed
50.
Chiyomaru T, Yamamura S, Fukuhara S, Yoshino H, Kinoshita T, Majid S, Saini S, Chang I, Tanaka Y, Enokida H, et al. Genistein inhibits prostate cancer cell growth by targeting miR-34a and oncogenic HOTAIR. PLoS ONE. 2013;8(8):e70372.CrossRefPubMedPubMedCentral
51.
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):3707–22.CrossRefPubMedPubMedCentral
52.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMed
53.
Huang L, Liao LM, Liu AW, Wu JB, Cheng XL, Lin JX, Zheng M. Overexpression of long noncoding RNA HOTAIR predicts a poor prognosis in patients with cervical cancer. Arch Gynecol Obstet. 2014;290:717–23.CrossRefPubMed
54.
Guo L, Lu X, Zheng L, Liu X, Hu M. Association of long non-coding RNA HOTAIR polymorphisms with cervical cancer risk in a Chinese population. PLoS ONE. 2016;11(7):e0160039.CrossRefPubMedPubMedCentral
55.
Qiu H, Liu Q, Li J, Wang X, Wang Y, Yuan Z, Li J, Pei DS. Analysis of the association of HOTAIR single nucleotide polymorphism (rs920778) and risk of cervical cancer. APMIS. 2016;124(7):567–73.CrossRefPubMed
56.
Yee GP, de Souza P, Khachigian LM. Current and potential treatments for cervical cancer. Curr Cancer Drug Targets. 2013;13(2):205–20.CrossRefPubMed
57.
Dutta S, Nguyen NP, Vock J, Kerr C, Godinez J, Bose S, Jang S, Chi A, Almeida F, Woods W, et al. Image-guided radiotherapy and -brachytherapy for cervical cancer. Front Oncol. 2015;5:64.PubMedPubMedCentral
58.
Li J, Wang Y, Yu J, Dong R, Qiu H. A high level of circulating HOTAIR is associated with progression and poor prognosis of cervical cancer. Tumour Biol. 2015;36:1661–5.CrossRefPubMed
59.
Jing L, Yuan W, Ruofan D, Jinjin Y, Haifeng Q. HOTAIR enhanced aggressive biological behaviors and induced radio-resistance via inhibiting p21 in cervical cancer. Tumour Biology. 2015;36(5):3611–9.CrossRefPubMed
Metadata
Title
HOTAIR: a key regulator in gynecologic cancers
Authors
Jing Li
Jing Wang
Yan Zhong
Ruixia Guo
Danxia Chu
Haifeng Qiu
Zhongfu Yuan
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0434-6

Other articles of this Issue 1/2017

Cancer Cell International 1/2017 Go to the issue

Primary Research

HNRNPA2B1 regulates the epithelial–mesenchymal transition in pancreatic cancer cells through the ERK/snail signalling pathway

Primary research

Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells

Retraction Note

Retraction Note to: Mutation pattern is an influential factor on functional mutation rates in cancer

Primary research

Overexpression of suppressor of zest 12 is associated with cervical node metastasis and unfavorable prognosis in tongue squamous cell carcinoma

Primary Research

EP300 single nucleotide polymorphism rs20551 correlates with prolonged overall survival in diffuse large B cell lymphoma patients treated with R-CHOP

Primary Research

MicroRNA-338-3p suppresses cell proliferation and induces apoptosis of non-small-cell lung cancer by targeting sphingosine kinase 2
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits