Difference between revisions of "NONHSAT028508"

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HOTAIR has been suggested to function at the chromatin level by interacting with chromatin modifying protein complexes <ref name="ref9" />. It has been reported that HOTAIR expression is correlated with SUZ12 expression level and therefore may affect the epigenetic state of cancer tissues<ref name="ref11" />. HOTAIR acts as a scaffold for protein complexes. A 5' domain binds PRC2 while a 3' domain binds LSD1<ref name="ref7" />. Oncogenic effects of HOTAIR upregulation were dependent on PRC2 <ref name="ref2" />.  
 
HOTAIR has been suggested to function at the chromatin level by interacting with chromatin modifying protein complexes <ref name="ref9" />. It has been reported that HOTAIR expression is correlated with SUZ12 expression level and therefore may affect the epigenetic state of cancer tissues<ref name="ref11" />. HOTAIR acts as a scaffold for protein complexes. A 5' domain binds PRC2 while a 3' domain binds LSD1<ref name="ref7" />. Oncogenic effects of HOTAIR upregulation were dependent on PRC2 <ref name="ref2" />.  
  
−
Oncogene - regulates metastatic progression in many kinds of cancers <ref name="ref2" /><ref name="ref5" /><ref name="ref18" /><ref name="ref12" /><ref name="ref3" /><ref name="ref11" />. It is crucial for cell growth and viability and its knockdown induced apoptosis in breast cancer cells<ref name="ref10" />. There was a great upregulation of HOTAIR in Esophageal squamous cell carcinoma (ESCC) compared to their adjacent normal esophageal tissues. Meanwhile, patients with high HOTAIR expression have a significantly poorer prognosis than those with low expression. Moreover, HOTAIR was further validated to promote migration and invasion of ESCC cells in vitro<ref name="ref18" />. Knockdown of HOTAIR decreased prostate cancer (PCa) cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest <ref name="ref12" />. High HOTAIR expression tightly correlated with the presence of liver metastasis and associated with poor prognosis <ref name="ref3" />. The aberrant expression of HOTAIR was associated with TNM staging and lymph node metastasis of gastric tumors<ref name="ref11" />.
+
Oncogene - regulates metastatic progression in many kinds of cancers <ref name="ref2" /><ref name="ref5" /><ref name="ref18" /><ref name="ref12" /><ref name="ref3" /><ref name="ref11" />. It is crucial for cell growth and viability and its knockdown induced apoptosis in breast cancer cells<ref name="ref10" />. There was a great upregulation of HOTAIR in Esophageal squamous cell carcinoma (ESCC) compared to their adjacent normal esophageal tissues. Meanwhile, patients with high HOTAIR expression have a significantly poorer prognosis than those with low expression. Moreover, HOTAIR was further validated to promote migration and invasion of ESCC cells in vitro<ref name="ref18" />. Knockdown of HOTAIR decreased prostate cancer (PCa) cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest <ref name="ref12" />. High HOTAIR expression tightly correlated with the presence of liver metastasis and associated with poor prognosis <ref name="ref3" />. The aberrant expression of HOTAIR was associated with TNM staging and lymph node metastasis of gastric tumors<ref name="ref11" />. Reduced expression of HOTAIR in KATO III suppressed peritoneal dissemination suggest that HOTAIR plays a pivotal role in the development of gastric cancer<ref name="ref14" />.
  
−
It is also highly correlated with malignant degree of cancer and the therapeutic effect <ref name="ref13" /><ref name="ref2" /><ref name="ref19" />.
+
It is also highly correlated with malignant degree of cancer and the therapeutic effect <ref name="ref13" /><ref name="ref2" /><ref name="ref19" /><ref name="ref15" /><ref name="ref17" />.
  
 
Deletion of the HoxC cluster containing the cognate Hotair transcript in mouse showed little phenotypic effect, with little change in the expression on levels of H3K27me3 coverage in corresponding human HOTAIR Hoxd target genes <ref name="ref5" />.
 
Deletion of the HoxC cluster containing the cognate Hotair transcript in mouse showed little phenotypic effect, with little change in the expression on levels of H3K27me3 coverage in corresponding human HOTAIR Hoxd target genes <ref name="ref5" />.
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In situ hybridization analysis of the mouse cognate RNA (mHotair) showed expression similar to Hoxc11, with distinct levels in parts of the proximal hindlimbs, genital bud and tail in embryos at E11.5, as well as in in posterior part of the hindlimb and genital bud at E12.5 <ref name="ref5" />.
 
In situ hybridization analysis of the mouse cognate RNA (mHotair) showed expression similar to Hoxc11, with distinct levels in parts of the proximal hindlimbs, genital bud and tail in embryos at E11.5, as well as in in posterior part of the hindlimb and genital bud at E12.5 <ref name="ref5" />.
  
−
It is up-regulated in breast cancer <ref name="ref2" /><ref name="ref10" />, colorectal cancer (CRC) <ref name="ref3" />. It is also up-regulated in breast cancer, Esophageal squamous cell carcinoma (ESCC) <ref name="ref18" />, ovarian cancer <ref name="ref13" />, gastric adenocarcinoma samples <ref name="ref11" />,Non-small-cell lung carcinoma (NSCLC) <ref name="ref19" />.
+
It is up-regulated in breast cancer <ref name="ref2" /><ref name="ref10" />, colorectal cancer (CRC) <ref name="ref3" />, Esophageal squamous cell carcinoma (ESCC) <ref name="ref18" />, ovarian cancer <ref name="ref13" />, gastric adenocarcinoma samples <ref name="ref11" />,Non-small-cell lung carcinoma (NSCLC) <ref name="ref19" />, laryngeal squamous cell cancer (LSCC) <ref name="ref15" />,cisplatin-resistant A549/DDP cells <ref name="ref16" />.
−
 
 
−
Reduced expression of HOTAIR in KATO III suppressed peritoneal dissemination suggest that HOTAIR plays a pivotal role in the development of gastric cancer<ref name="ref14" />. HOTAIR plays an oncogenic role in human laryngeal squamous cell cancer (LSCC),HOTAIR levels were significantly higher in LSCC than in corresponding adjacent non-neoplastic tissues,HOTAIR is an independent prognostic factor of LSCC<ref name="ref15" />. HOTAIR expression was significantly upregulated in cisplatin-resistant A549/DDP cells compared with in parental A549 cells. Knockdown of HOTAIR by RNA interference could resensitize the responses of A549/DDP cells to cisplatin both in vitro and in vivo. In contrast, overexpression of HOTAIR could decrease the sensitivity of A549 and SPC-A1 cells to cisplatin. We also found that the siRNA/HOTAIR1-mediated chemosensivity enhancement was associated with inhibition of cell proliferation, induction of G0/G1 cell-cycle arrest and apoptosis enhancement through regulation of p21(WAF1/CIP1) (p21) expression. Also, pcDNA/p21or siRNA/p21 could mimic the effects of siRNA/HOTAIR1 or pcDNA/HOTAIR on the sensitivity of LAD cells to cisplatin. Importantly, siRNA/p21 or pcDNA/p21 could partially rescue the effects of siRNA/HOTAIR1 or pcDNA/HOTAIR on both p21 expression and cisplatin sensitivity in LAD cells. Further, HOTAIR was observed to be significantly downregulated in cisplatin-responding LAD tissues, and its expression was inversely correlated with p21 mRNA expression. Taken together, our findings suggest that upregulation of HOTAIR contributes to the cisplatin resistance of LAD cells, at least in part, through the regulation of p21 expression <ref name="ref16" />.HOTAIR is a potential biomarker for ESCC prognosis, and the dysregulation of HOTAIR may play an important role in ESCC progression<ref name="ref17" />.
 
  
 
===Conservation===
 
===Conservation===

Revision as of 09:15, 14 October 2014

Please input one-sentence summary here.

Annotated Information

Name

HOTAIR: Hox antisense intergenic RNA

Characteristics

2.2 kb; spliced, polyadenylated and comprised of 6 exons in humans [1].

Transcribed from the HOXC locus from a position intergenic and antisense to the flanking HOXC11 and HOXC12 genes [1].

Some HOTAIR transcripts localise to the nucleus [2].

Transcript found to be quite unstable with a half-life >4 hr in human Hela cells[3].

Function

Originally identified as silencing the HoxD locus but has since been found to epigenetic silence gene expression at many sites across the genome by recruitment of PRC2 and LSD1/CoREST/REST repressive chromatin modifying complexes [1][4].

HOTAIR has been suggested to function at the chromatin level by interacting with chromatin modifying protein complexes [5]. It has been reported that HOTAIR expression is correlated with SUZ12 expression level and therefore may affect the epigenetic state of cancer tissues[6]. HOTAIR acts as a scaffold for protein complexes. A 5' domain binds PRC2 while a 3' domain binds LSD1[4]. Oncogenic effects of HOTAIR upregulation were dependent on PRC2 [7].

Oncogene - regulates metastatic progression in many kinds of cancers [7][8][9][10][11][6]. It is crucial for cell growth and viability and its knockdown induced apoptosis in breast cancer cells[12]. There was a great upregulation of HOTAIR in Esophageal squamous cell carcinoma (ESCC) compared to their adjacent normal esophageal tissues. Meanwhile, patients with high HOTAIR expression have a significantly poorer prognosis than those with low expression. Moreover, HOTAIR was further validated to promote migration and invasion of ESCC cells in vitro[9]. Knockdown of HOTAIR decreased prostate cancer (PCa) cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest [10]. High HOTAIR expression tightly correlated with the presence of liver metastasis and associated with poor prognosis [11]. The aberrant expression of HOTAIR was associated with TNM staging and lymph node metastasis of gastric tumors[6]. Reduced expression of HOTAIR in KATO III suppressed peritoneal dissemination suggest that HOTAIR plays a pivotal role in the development of gastric cancer[13].

It is also highly correlated with malignant degree of cancer and the therapeutic effect [14][7][15][16][17].

Deletion of the HoxC cluster containing the cognate Hotair transcript in mouse showed little phenotypic effect, with little change in the expression on levels of H3K27me3 coverage in corresponding human HOTAIR Hoxd target genes [8].

HOTAIR acts as an inducer of ubiquitin-mediated proteolysis on post-translational function[18]. HOTAIR associates with E3 ubiquitin ligases bearing RNA-binding domains, Dzip3 and Mex3b, as well as with their respective ubiquitination substrates, Ataxin-1 and Snurportin-1. HOTAIR levels are highly upregulated in senescent cells, causing rapid decay of targets Ataxin-1 and Snurportin-1, and preventing premature senescence[18].

Expression

Expressed in posterior and distal fibroblasts [1].

In situ hybridization analysis of the mouse cognate RNA (mHotair) showed expression similar to Hoxc11, with distinct levels in parts of the proximal hindlimbs, genital bud and tail in embryos at E11.5, as well as in in posterior part of the hindlimb and genital bud at E12.5 [8].

It is up-regulated in breast cancer [7][12], colorectal cancer (CRC) [11], Esophageal squamous cell carcinoma (ESCC) [9], ovarian cancer [14], gastric adenocarcinoma samples [6],Non-small-cell lung carcinoma (NSCLC) [15], laryngeal squamous cell cancer (LSCC) [16],cisplatin-resistant A549/DDP cells [19].

Conservation

HOTAIR exists in mammals but with poor sequence conservation [1].[20]. A 239 bp domain in HOTAIR exon 6 is especially conserved in mammals [20].

The mouse EST (AK035706) homologous to human HOTAIR is comprised of two exons only, with the second half of the first exon showing similarity to exon 4 of HOTAIR, whereas the second exon is homologous to exon 6 of HOTAIR [8]. This may underlie differences in function since the first three exons of HOTAIR (absent from mHotair) contain binding sites for EZH2, while the 3' extremity of human HOTAIR that interact with LSD1 is part of the least conserved DNA sequence within mHotair exon 2 [8].

Regulation

HOTAIR is transcriptionally induced by estradiol (E2). Similar to protein-coding gene transcription, E2-induced transcription of antisense transcript HOTAIR is coordinated via ERs and ER coregulators, and this mechanism of HOTAIR overexpression potentially contributes towards breast cancer progression[12]. The long non-coding RNA HOTAIR has been reported to be a poor prognostic biomarker in a variety of malignant tumors[13].

LncRNA profiling showed that HOTAIR was highly regulated by genistein and its expression was higher in castration-resistant PCa cell lines than in normal prostate cells. miR-34a was also up-regulated by genistein and may directly target HOTAIR in both PC3 and DU145 PCa cells[10].

There is site-specific cytosine methylation in the lncRNA HOTAIR. Methylation of C1683 may affect the ability of HOTAIR to interact with LSD1[5].

Allelic Information and Variation

Please input allelic information and variation information here.

You can also add sub-section(s) at will.

Labs working on this lncRNA

Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, Maryland 21224, USA[18].

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Rinn JL1, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY.(2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs.Cell. 2007 Jun 29;129(7):1311-23.
  2. ↑ Khalil AM1, 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. (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11667-72. doi: 10.1073/pnas.0904715106. Epub 2009 Jul 1.
  3. ↑ Tani H1, Mizutani R, Salam KA, Tano K, Ijiri K, Wakamatsu A, Isogai T, Suzuki Y, Akimitsu N.(2012) Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals.Genome Res. 2012 May;22(5):947-56. doi: 10.1101/gr.130559.111. Epub 2012 Feb 27.
  4. ↑ 4.0 4.1 Tsai MC1, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY.(2010) Long noncoding RNA as modular scaffold of histone modification complexes.Science. 2010 Aug 6;329(5992):689-93. doi: 10.1126/science.1192002. Epub 2010 Jul 8.
  5. ↑ 5.0 5.1 Thomas Amort, Marie F. Soulière, Alexandra Wille, Xi-Yu Jia, Heidi Fiegl, Hildegard Wörle, Ronald Micura, Alexandra Lusser. (2013) Long non-coding RNAs as targets for cytosine methylation.PLoS One. 2013 May 23;8(5):e63516. doi: 10.1371/journal.pone.0063516. Print 2013.
  6. ↑ 6.0 6.1 6.2 6.3 Hajjari M1, Behmanesh M, Sadeghizadeh M, Zeinoddini M.(2013)Up-regulation of HOTAIR long non-coding RNA in human gastric adenocarcinoma tissues.Med Oncol. 2013;30(3):670. doi: 10.1007/s12032-013-0670-0. Epub 2013 Jul 26.
  7. ↑ 7.0 7.1 7.2 7.3 Gupta RA1, 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. (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis.Nature. 2010 Apr 15;464(7291):1071-6. doi: 10.1038/nature08975.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 Schorderet P1, Duboule D.(2011)Structural and functional differences in the long non-coding RNA hotair in mouse and human. PLoS Genet. 2011 May;7(5):e1002071. doi: 10.1371/journal.pgen.1002071. Epub 2011 May 26.
  9. ↑ 9.0 9.1 9.2 Ge XS1, Ma HJ, Zheng XH, Ruan HL, Liao XY, Xue WQ, Chen YB, Zhang Y, Jia WH.(2013) HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway.Cancer Sci. 2013 Dec;104(12):1675-82. doi: 10.1111/cas.12296. Epub 2013 Oct 30.
  10. ↑ 10.0 10.1 10.2 Chiyomaru T1, Yamamura S, Fukuhara S, Yoshino H, Kinoshita T, Majid S, Saini S, Chang I, Tanaka Y, Enokida H, Seki N, Nakagawa M, Dahiya R.(2013)Genistein inhibits prostate cancer cell growth by targeting miR-34a and oncogenic HOTAIR. PLoS One. 2013 Aug 1;8(8):e70372. doi: 10.1371/journal.pone.0070372. Print 2013.
  11. ↑ 11.0 11.1 11.2 Kogo R1, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, Tanaka F, Shibata K, Suzuki A, Komune S, Miyano S, Mori M. (2013) Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011 Oct 15;71(20):6320-6. doi: 10.1158/0008-5472.CAN-11-1021. Epub 2011 Aug 23.
  12. ↑ 12.0 12.1 12.2 Bhan A1, Hussain I, Ansari KI, Kasiri S, Bashyal A, Mandal SS. (2013) Antisense transcript long noncoding RNA (lncRNA) HOTAIR is transcriptionally induced by estradiol. J Mol Biol. 2013 Oct 9;425(19):3707-22. doi: 10.1016/j.jmb.2013.01.022. Epub 2013 Jan 31.
  13. ↑ 13.0 13.1 Endo H1, 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.(2013) Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. PLoS One. 2013 Oct 10;8(10):e77070. doi: 10.1371/journal.pone.0077070. eCollection 2013.
  14. ↑ 14.0 14.1 Cui L1, Xie XY, Wang H, Chen XL, Liu SL, Hu LN.(2013)[Expression of long non-coding RNA HOTAIR mRNA in ovarian cancer].Sichuan Da Xue Xue Bao Yi Xue Ban. 2013 Jan;44(1):57-9.
  15. ↑ 15.0 15.1 Liu XH1, Liu ZL, Sun M, Liu J, Wang ZX, De W.(2013) The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer. BMC Cancer. 2013 Oct 8;13:464. doi: 10.1186/1471-2407-13-464.
  16. ↑ 16.0 16.1 Li D1, Feng J, Wu T, Wang Y, Sun Y, Ren J, Liu M.(2013)Long intergenic noncoding RNA HOTAIR is overexpressed and regulates PTEN methylation in laryngeal squamous cell carcinoma.Am J Pathol. 2013 Jan;182(1):64-70. doi: 10.1016/j.ajpath.2012.08.042. Epub 2012 Nov 7.
  17. ↑ Lv XB1, Lian GY, Wang HR, Song E, Yao H, Wang MH.(2013) Long noncoding RNA HOTAIR is a prognostic marker for esophageal squamous cell carcinoma progression and survival.PLoS One. 2013 May 23;8(5):e63516. doi: 10.1371/journal.pone.0063516. Print 2013.
  18. ↑ 18.0 18.1 18.2 Yoon JH1, Abdelmohsen K, Kim J, Yang X, Martindale JL, Tominaga-Yamanaka K, White EJ, Orjalo AV, Rinn JL, Kreft SG, Wilson GM, Gorospe M.(2013) Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination.Nat Commun. 2013;4:2939. doi: 10.1038/ncomms3939.
  19. ↑ Liu Z1, Sun M, Lu K, Liu J, Zhang M, Wu W, De W, Wang Z, Wang R.(2013)The long noncoding RNA HOTAIR contributes to cisplatin resistance of human lung adenocarcinoma cells via downregualtion of p21(WAF1/CIP1) expression. PLoS One. 2013 Oct 14;8(10):e77293. doi: 10.1371/journal.pone.0077293. eCollection 2013.
  20. ↑ 20.0 20.1 He S1, Liu S, Zhu H.(2011) The sequence, structure and evolutionary features of HOTAIR in mammals. BMC Evol Biol. 2011 Apr 16;11:102. doi: 10.1186/1471-2148-11-102.


Basic Information

Transcript ID

NONHSAT028508

Source

NONCODE4.0

Same with

,

Classification

intergenic

Length

2337 nt

Genomic location

chr12-:54356092..54362540

Exon number

6

Exons

54356092..54357908,54358015..54358067,54359748..54359871,54360060..54360161,54361053..54361178,54362401..54362540

Genome context

Sequence
000001 ACATTCTGCC CTGATTTCCG GAACCTGGAA GCCTAGGCAG GCAGTGGGGA ACTCTGACTC GCCTGTGCTC TGGAGCTTGA 000080
000081 TCCGAAAGCT TCCACAGTGA GGACTGCTCC GTGGGGGTAA GAGAGCACCA GGCACTGAGG CCTGGGAGTT CCACAGACCA 000160
000161 ACACCCCTGC TCCTGGCGGC TCCCACCCGG GACTTAGACC CTCAGGTCCC TAATATCCCG GAGGTGCTCT CAATCAGAAA 000240
000241 GGTCCTGCTC CGCTTCGCAG TGGAATGGAA CGGATTTAGA AGCCTGCAGT AGGGGAGTGG GGAGTGGAGA GAGGGAGCCC 000320
000321 AGAGTTACAG ACGGCGGCGA GAGGAAGGAG GGGCGTCTTT ATTTTTTTAA GGCCCCAAAG AGTCTGATGT TTACAAGACC 000400
000401 AGAAATGCCA CGGCCGCGTC CTGGCAGAGA AAAGGCTGAA ATGGAGGACC GGCGCCTTCC TTATAAGTAT GCACATTGGC 000480
000481 GAGAGAAGTG CTGCAACCTA AACCAGCAAT TACACCCAAG CTCGTTGGGG CCTAAGCCAG TACCGACCTG GTAGAAAAAG 000560
000561 CAACCACGAA GCTAGAGAGA GAGCCAGAGG AGGGAAGAGA GCGCCAGACG AAGGTGAAAG CGAACCACGC AGAGAAATGC 000640
000641 AGGCAAGGGA GCAAGGCGGC AGTTCCCGGA ACAAACGTGG CAGAGGGCAA GACGGGCACT CACAGACAGA GGTTTATGTA 000720
000721 TTTTTATTTT TTAAAATCTG ATTTGGTGTT CCATGAGGAA AAGGGAAAAT CTAGGGAACG GGAGTACAGA GAGAATAATC 000800
000801 CGGGTCCTAG CTCGCCACAT GAACGCCCAG AGAACGCTGG AAAAACCTGA GCGGGTGCCG GGGCAGCACC CGGCTCGGGT 000880
000881 CAGCCACTGC CCCACACCGG GCCCACCAAG CCCCGCCCCT CGCGGCCACC GGGGCTTCCT TGCTCTTCTT ATCATCTCCA 000960
000961 TCTTTATGAT GAGGCTTGTT AACAAGACCA GAGAGCTGGC CAAGCACCTC TATCTCAGCC GCGCCCGCTC AGCCGAGCAG 001040
001041 CGGTCGGTGG GGGGACTGGG AGGCGCTAAT TAATTGATTC CTTTGGACTG TAAAATATGG CGGCGTCTAC ACGGAACCCA 001120
001121 TGGACTCATA AACAATATAT CTGTTGGGCG TGAGTGCACT GTCTCTCAAA TAATTTTTCC ATAGGCAAAT GTCAGAGGGT 001200
001201 TCTGGATTTT T