Skip to main content

Advertisement

SpringerLink
Log in

Contributions of HOTAIR polymorphisms to the susceptibility of cancer

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Objective

Hox transcript antisense intergenic RNA (HOTAIR), a lncRNA, functions as a critical regulator in cancer development. A plenty of case–control studies were conducted to assess the actual relationship of HOTAIR gene generic variants on cancer susceptibility, yet conflicting conclusions remain. Herein, we carried out this up-to-date meta-analysis to get a better understanding of such relationship by incorporating all eligible case–control studies.

Materials and methods

Six widely investigated polymorphisms were included in this meta-analysis: rs920778, rs4759314, rs7958904, rs874945, rs1899663, and rs12826786. We retrieved relevant studies from databases PubMed, EMBASE, Medline, CNKI and Wanfang update to June 2020. We applied odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the relationship strengths.

Results

Our findings indicate that rs920778, rs4759314, rs874945, rs12826786 polymorphism significantly increased with susceptibility to overall cancer. However, rs7958904, rs1899663 under any five genetic models could not impact susceptibility to overall cancer. Furthermore, altered cancer risk was detected when the data were stratified by cancer type, ethnicity, the source of controls, and HWE in all the SNPs.

Conclusions

These findings of the meta-analysis suggest that HOTAIR polymorphisms may predispose to cancer susceptibility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  Google Scholar 

  2. Erichsen HC, Chanock SJ (2004) SNPs in cancer research and treatment. Br J Cancer 90:747–751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Theodoratou E, Timofeeva M, Li X, Meng X et al (2017) Nature, nurture, and cancer risks: genetic and nutritional contributions to cancer. Annu Rev Nutr 37:293–320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Malhotra J (2014) Molecular and genetic epidemiology of cancer in low- and medium-income countries. Ann Glob Health 80:418–425

    Article  PubMed  Google Scholar 

  5. Bhan A, Soleimani M, Mandal SS (2017) Long noncoding RNA and cancer: a new paradigm. Cancer Res 77:3965–3981

    Article  CAS  PubMed  Google Scholar 

  6. Renganathan A, Felley-Bosco E (2017) Long noncoding RNAs in cancer and therapeutic potential. Adv Exp Med Biol 1008:199–222

    Article  CAS  PubMed  Google Scholar 

  7. Wang Y, He H, Li W et al (2017) MYH9 binds to lncRNA gene PTCSC2 and regulates FOXE1 in the 9q22 thyroid cancer risk locus. Proc Natl Acad Sci U S A 114:474–479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Guo H, Ahmed M, Zhang F et al (2016) Modulation of long noncoding RNAs by risk SNPs underlying genetic predispositions to prostate cancer. Nat Genet 48:1142–1150

    Article  CAS  PubMed  Google Scholar 

  9. Pandey GK, Mitra S, Subhash S et al (2014) The risk-associated long noncoding RNA NBAT-1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation. Cancer Cell 26:722–737

    Article  CAS  PubMed  Google Scholar 

  10. Ling H, Spizzo R, Atlasi Y et al (2013) CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. Genome Res 23:1446–1461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hua JT, Ahmed M, Guo H et al (2018) Risk SNP-mediated promoter-enhancer switching drives prostate cancer through lncRNA PCAT19. Cell 174(564–575):e518

    Google Scholar 

  12. Zhuo ZJ, Liu W, Zhang J et al (2018) Functional polymorphisms at ERCC1/XPF genes confer neuroblastoma risk in Chinese children. EBioMedicine 30:113–119

    Article  PubMed  PubMed Central  Google Scholar 

  13. Shah MY, Ferracin M, Pileczki V (2018) Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations. Genome Res 28:432–447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gupta RA, Shah N, Wang KC et al (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464:1071–1076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rinn JL, Kertesz M, Wang JK et al (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311–1323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kogo R, Shimamura T, Mimori K et al (2011) Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res 71:6320–6326

    Article  CAS  PubMed  Google Scholar 

  17. Tsai MC, Manor O, Wan Y et al (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329:689–693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Liu XH, Sun M, Nie FQ et al (2014) Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer 13:92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cai H, Yao J, An Y et al (2017) LncRNA HOTAIR acts a competing endogenous RNA to control the expression of notch3 via sponging miR-613 in pancreatic cancer. Oncotarget 8:32905–32917

    Article  PubMed  PubMed Central  Google Scholar 

  20. Tang Q, Hann SS (2018) HOTAIR: an oncogenic long non-coding RNA in human cancer. Cell Physiol Biochem 47:893–913

    Article  CAS  PubMed  Google Scholar 

  21. Zhang X, Zhou L, Fu G et al (2014) The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic enhancer. Carcinogenesis 35:2062–2067

    Article  CAS  PubMed  Google Scholar 

  22. Bayram S, Sumbul AT, Batmaci CY et al (2015) Effect of HOTAIR rs920778 polymorphism on breast cancer susceptibility and clinicopathologic features in a Turkish population. Tumour Biol 36:3863–3870

    Article  CAS  PubMed  Google Scholar 

  23. Bayram S, Ulger Y, Sumbul AT et al (2015) A functional HOTAIR rs920778 polymorphism does not contributes to gastric cancer in a Turkish population: a case-control study. Fam Cancer 14:561–567

    Article  CAS  PubMed  Google Scholar 

  24. Du M, Wang W, Jin H et al (2015) The association analysis of lncRNA HOTAIR genetic variants and gastric cancer risk in a Chinese population. Oncotarget 6:31255–31262

    Article  PubMed  PubMed Central  Google Scholar 

  25. Guo W, Dong Z, Bai Y et al (2015) Associations between polymorphisms of HOTAIR and risk of gastric cardia adenocarcinoma in a population of north China. Tumour Biol 36:2845–2854

    Article  CAS  PubMed  Google Scholar 

  26. Xue Y, Gu D, Ma G et al (2015) Genetic variants in lncRNA HOTAIR are associated with risk of colorectal cancer. Mutagenesis 30:303–310

    Article  CAS  PubMed  Google Scholar 

  27. Yan R, Cao J, Song C et al (2015) Polymorphisms in lncRNA HOTAIR and susceptibility to breast cancer in a Chinese population. Cancer Epidemiol 39:978–985

    Article  PubMed  Google Scholar 

  28. Bayram S, Sumbul AT, Dadas E (2016) A functional HOTAIR rs12826786 C>T polymorphism is associated with breast cancer susceptibility and poor clinicopathological characteristics in a Turkish population: a hospital-based case-control study. Tumour Biol 37:5577–5584

    Article  CAS  PubMed  Google Scholar 

  29. Gong WJ, Yin JY, Li XP et al (2016) Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response. Tumour Biol 37:8349–8358

    Article  CAS  PubMed  Google Scholar 

  30. Guo L, Lu X, Zheng L et al (2016) Association of long non-coding RNA HOTAIR polymorphisms with cervical cancer risk in a Chinese population. PLoS ONE 11:e0160039

    Article  PubMed  PubMed Central  Google Scholar 

  31. Pan W, Liu L, Wei J et al (2016) A functional lncRNA HOTAIR genetic variant contributes to gastric cancer susceptibility. Mol Carcinog 55:90–96

    Article  CAS  PubMed  Google Scholar 

  32. Qiu H, Liu Q, Li J et al (2016) Analysis of the association of HOTAIR single nucleotide polymorphism (rs920778) and risk of cervical cancer. APMIS 124:567–573

    Article  CAS  PubMed  Google Scholar 

  33. Wu H, Shang X, Shi Y et al (2016) Genetic variants of lncRNA HOTAIR and risk of epithelial ovarian cancer among Chinese women. Oncotarget 7:41047–41052

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zhou Q, Chen F, Fei Z et al (2016) Genetic variants of lncRNA HOTAIR contribute to the risk of osteosarcoma. Oncotarget 7:19928–19934

    Article  PubMed  PubMed Central  Google Scholar 

  35. Zhou Z, Bingqiang N, Rixin C et al (2016) LncRNA HOTAIR polymorphisms and the sucesptability and prognosis of colorectal cancer. Guangdong Med J 37:2916–2919

    CAS  Google Scholar 

  36. Zhu H, Lv Z, An C et al (2016) Onco-lncRNA HOTAIR and its functional genetic variants in papillary thyroid carcinoma. Sci Rep 6:31969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hassanzarei S, Hashemi M, Sattarifard H et al (2017) Genetic polymorphisms of HOTAIR gene are associated with the risk of breast cancer in a sample of southeast Iranian population. Tumour Biol 39:1010428317727539

    Article  PubMed  Google Scholar 

  38. Hu P, Qiao O, Wang J et al (2017) rs1859168 A > C polymorphism regulates HOTTIP expression and reduces risk of pancreatic cancer in a Chinese population. World J Surg Oncol 15:155

    Article  PubMed  PubMed Central  Google Scholar 

  39. Jin H, Lu X, Ni J et al (2017) HOTAIR rs7958904 polymorphism is associated with increased cervical cancer risk in a Chinese population. Sci Rep 7:3144

    Article  PubMed  PubMed Central  Google Scholar 

  40. Li H, Tang XM, Liu Y et al (2017) Association of functional genetic variants of HOTAIR with hepatocellular carcinoma (HCC) susceptibility in a Chinese population. Cell Physiol Biochem 44:447–454

    Article  CAS  PubMed  Google Scholar 

  41. Qiu H, Wang X, Guo R et al (2017) HOTAIR rs920778 polymorphism is associated with ovarian cancer susceptibility and poor prognosis in a Chinese population. Future Oncol 13:347–355

    Article  CAS  PubMed  Google Scholar 

  42. Taheri M, Habibi M, Noroozi R et al (2017) HOTAIR genetic variants are associated with prostate cancer and benign prostate hyperplasia in an Iranian population. Gene 613:20–24

    Article  CAS  PubMed  Google Scholar 

  43. Ulger Y, Dadas E, Yalinbas Kaya B et al (2017) The analysis of lncRNA HOTAIR rs12826786 C>T polymorphism and gastric cancer susceptibility in a Turkish population: lack of any association in a hospital-based case-control study. Ir J Med Sci 186:859–865

    Article  CAS  PubMed  Google Scholar 

  44. Xavier-Magalhaes A, Oliveira AI, de Castro JV et al (2017) Effects of the functional HOTAIR rs920778 and rs12826786 genetic variants in glioma susceptibility and patient prognosis. J Neurooncol 132:27–34

    Article  CAS  PubMed  Google Scholar 

  45. Li H, Yang Z, Li J et al (2018) Genetic variants in lncRNA HOTAIR are associated with lung cancer susceptibility in a Chinese Han population in China: a case-control study. Cancer Manag Res 10:5209–5218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Oliveira AI, Xavier-Magalhaes A, Moreira-Barbosa C et al (2018) Influence of HOTAIR rs920778 and rs12826786 genetic variants on prostate cancer risk and progression-free survival. Biomark Med 12:257–264

    Article  CAS  PubMed  Google Scholar 

  47. Su SC, Hsieh MJ, Lin CW et al (2018) Impact of HOTAIR gene polymorphism and environmental risk on oral cancer. J Dent Res 97:717–724

    Article  CAS  PubMed  Google Scholar 

  48. Wang C, Li Y, Li YW et al (2018) HOTAIR lncRNA SNPs rs920778 and rs1899663 are associated with smoking, male gender, and squamous cell carcinoma in a Chinese lung cancer population. Acta Pharmacol Sin 39:1797–1803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Weng SL, Wu WJ, Hsiao YH et al (2018) Significant association of long non-coding RNAs HOTAIR genetic polymorphisms with cancer recurrence and patient survival in patients with uterine cervical cancer. Int J Med Sci 15:1312–1319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wu B, Liu J, Wang B et al (2018) Association on polymorphisms in LncRNA HOTAIR and susceptibility to HNSCC in Chinese population. Eur Rev Med Pharmacol Sci 22:702–706

    CAS  PubMed  Google Scholar 

  51. Yang X, He J, Chang Y et al (2018) HOTAIR gene polymorphisms contribute to increased neuroblastoma susceptibility in Chinese children. Cancer 124:2599–2606

    Article  CAS  PubMed  Google Scholar 

  52. Farzaneh F, Saravani M, Esmailpoor M et al (2019) Association of HOTAIR gene polymorphisms and haplotypes with uterine leiomyoma susceptibility in southeast of Iran. Mol Biol Rep 46:4271–4277

    Article  CAS  PubMed  Google Scholar 

  53. Jiang D, Xu L, Ni J et al (2019) Functional polymorphisms in LncRNA HOTAIR contribute to susceptibility of pancreatic cancer. Cancer Cell Int 19:47

    Article  PubMed  PubMed Central  Google Scholar 

  54. Li Y, Yaning F, Yanjie Y et al (2019) Association between polymorphisms of HOTAIR and risk of gastric cancer in a population in Ningxia, China. World J Gastroenterol 27:29–35

    Google Scholar 

  55. Moschovis D, Vasilaki E, Tzouvala M et al (2019) Association between genetic polymorphisms in long non-coding RNAs and pancreatic cancer risk. Cancer Biomark 24:117–123

    Article  CAS  PubMed  Google Scholar 

  56. Tung MC, Wen YC, Wang SS et al (2019) Impact of long non-coding RNA HOTAIR genetic variants on the susceptibility and clinicopathologic characteristics of patients with urothelial cell carcinoma. J Clin Med 8:282

    Article  CAS  PubMed Central  Google Scholar 

  57. Yeqiong X, Yanhong C, Yilin Z et al (2019) HOTAIR gene polymorphism and colorectal cancer risk. Chin J Clin Lab Sci 37:364–368

    Google Scholar 

  58. Zhang J, Liu L, Lin Z et al (2019) SNP-SNP and SNP-environment interactions of potentially functional HOTAIR SNPs modify the risk of hepatocellular carcinoma. Mol Carcinog 58:633–642

    Article  CAS  PubMed  Google Scholar 

  59. Deng ZH, Yu GS, Pan B et al (2020) Rs145204276 and rs4759314 affect the prognosis of prostate cancer by modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways. Artif Cells Nanomed Biotechnol 48:435–442

    Article  CAS  PubMed  Google Scholar 

  60. Kim JO, Jun HH, Kim EJ et al (2020) Genetic variants of HOTAIR associated with colorectal cancer susceptibility and mortality. Front Oncol 10:72

    Article  PubMed  PubMed Central  Google Scholar 

  61. Minn AKK, Sato N, Mieno MN et al (2020) Association study of long non-coding RNA HOTAIR rs920778 polymorphism with the risk of cancer in an elderly Japanese population. Gene 729:144263

    Article  PubMed  Google Scholar 

  62. Qu X, Alsager S, Zhuo Y et al (2019) HOX transcript antisense RNA (HOTAIR) in cancer. Cancer Lett 454:90–97

    Article  CAS  PubMed  Google Scholar 

  63. Zhang ZX, Tong X, Zhang WN et al (2017) Association between the HOTAIR polymorphisms and cancer risk: an updated meta-analysis. Oncotarget 8:4460–4470

    Article  PubMed  Google Scholar 

  64. Xu T, Zhou Y, Zhang Y et al (2019) Association between HOTAIR polymorphisms and cancer riska meta-analysis based on twenty-one case-control studies. J BUON 24:354–367

    PubMed  Google Scholar 

Download references

Funding

This study was supported by grant from Guiding Project of Scientific Research Program of Hubei Education Department in 2019 (B2019106), Health Commission of Hubei Province scientific research project (No: WJ2021F039), Education Commission of Hubei Province Scientific Research Project (No: B2020103).

Author information

Author notes

  1. Hu-Nian Li and Na Deng have contributed equally.

Authors and Affiliations

  1. Emergency and Critical Care Center, Renmin Hospital, Hubei University of Medicine, No. 37 Chaoyang Middle Road, Shiyan, 442000, Hubei, China

    Hu-Nian Li, Xu Zhao & Jie Liu

  2. Children’s Medical Center, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Na Deng & Xi-Wei Ding

  3. Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Ting He

Authors
  1. Hu-Nian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Na Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jie Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ting He
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xi-Wei Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ting He or Xi-Wei Ding.

Ethics declarations

Conflict of interests

No author has any conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, HN., Deng, N., Zhao, X. et al. Contributions of HOTAIR polymorphisms to the susceptibility of cancer. Int J Clin Oncol 26, 1022–1038 (2021). https://doi.org/10.1007/s10147-021-01884-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-021-01884-1

Keywords

Search

Navigation