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Nazari M, Babakhanzadeh E, Mollazadeh A, Ahmadzade M, Mohammadi Soleimani E, Hajimaqsoudi E. HOTAIR in cancer: diagnostic, prognostic, and therapeutic perspectives. Cancer Cell Int 2024; 24:415. [PMID: 39702144 DOI: 10.1186/s12935-024-03612-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 12/11/2024] [Indexed: 12/21/2024] Open
Abstract
The long non-coding RNA HOTAIR is overexpressed in many cancers and is associated with several cancer-promoting effects, including increased cell proliferation, migration and treatment resistance. HOTAIR levels correlate with tumor stage, lymph node metastasis and overall survival in patients with various types of cancer. This highlights the potential uses of HOTAIR, including early cancer detection, predicting patient outcome, identifying high-risk individuals and assisting in therapy selection and monitoring. The aim of this review is to provide a comprehensive summary of the research progress, molecular mechanisms and clinical significance of HOTAIR in various human cancers. In addition, the clinical applications of HOTAIR, such as targeted therapy, radiotherapy, chemotherapy and immunotherapy, are discussed, and relevant information on the potential future advances of HOTAIR in cancer research is provided.
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Affiliation(s)
- Majid Nazari
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, P.O. Box 64155-65117, Tehran, Yazd, Iran.
| | - Emad Babakhanzadeh
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arghavan Mollazadeh
- Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL, 60115, USA
| | - Mohadese Ahmadzade
- Department of Urology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Elnaz Hajimaqsoudi
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Krishna BM, Garg P, Ramisetty S, Subbalakshmi AR, Kulkarni P, Salgia R, Singhal SS. Comprehensive investigation of long non-coding RNA HOTAIR polymorphisms and cancer risk: a current meta-analysis encompassing 96,458 participants. Sci Rep 2024; 14:22670. [PMID: 39349529 PMCID: PMC11442654 DOI: 10.1038/s41598-024-72586-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 09/09/2024] [Indexed: 10/02/2024] Open
Abstract
Cancer ranks as the second leading cause of mortality worldwide, prompting extensive investigations into factors contributing to its development. Among these factors, genetic variations, known as genotypic polymorphisms, have been identified as significant influencers in the susceptibility to various types of cancer. Recent research has focused on exploring the connection between polymorphisms in the Long Non-coding RNA HOTAIR and cancer risk. However, the results from these studies have been inconsistent, leading to ambiguity and controversy. To address this uncertainty, we conducted a systematic analysis by gathering relevant studies from PubMed, EMBASE, and Google Scholar. Specifically, we focused on three well-studied polymorphisms within the HOTAIR lncRNA (HOTAIR rs920778 C > T, HOTAIR rs1899663 G > T, HOTAIR rs4759314 A > G) and their association with cancer risk. Our meta-analysis included data from 48 case-control studies involving 42,321 cases and 54,137 controls. The results of our updated meta-analysis revealed a significant correlation between HOTAIR rs1899663 G > T and HOTAIR rs4759314 A > G polymorphisms and overall cancer risk, particularly in the homozygous and recessive genetic models. Subgroup analysis further revealed that these associations were notably pronounced in the Asian population but not observed in the Iranian population. Furthermore, our findings underscore the potential of HOTAIR polymorphisms as diagnostic markers for overall cancer risk, particularly in gynecological cancers, precisely, HOTAIR rs1899663 G > T polymorphism in breast cancer. In conclusion, our systematic analysis provides compelling evidence that Long Non-coding RNA HOTAIR polymorphisms are linked to cancer risk, particularly in certain populations and cancer types, suggesting their potential clinical relevance as diagnostic indicators.
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Affiliation(s)
- B Madhu Krishna
- Department of Medical Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center and National Medical Center, Duarte, CA, 91010, USA
| | - Pankaj Garg
- Department of Chemistry, GLA University, Mathura, Uttar Pradesh, 281406, India
| | - Sravani Ramisetty
- Department of Medical Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center and National Medical Center, Duarte, CA, 91010, USA
| | - Ayalur Raghu Subbalakshmi
- Department of Medical Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center and National Medical Center, Duarte, CA, 91010, USA
| | - Prakash Kulkarni
- Department of Chemistry, GLA University, Mathura, Uttar Pradesh, 281406, India
| | - Ravi Salgia
- Department of Medical Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center and National Medical Center, Duarte, CA, 91010, USA
| | - Sharad S Singhal
- Department of Medical Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center and National Medical Center, Duarte, CA, 91010, USA.
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Martins EP, Vieira de Castro J, Fontes R, Monteiro-Reis S, Henrique R, Jerónimo C, Costa BM. Relevance of HOTAIR rs920778 and rs12826786 Genetic Variants in Bladder Cancer Risk and Survival. Cancers (Basel) 2024; 16:434. [PMID: 38275875 PMCID: PMC10814037 DOI: 10.3390/cancers16020434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/12/2024] [Accepted: 01/16/2024] [Indexed: 01/27/2024] Open
Abstract
The long non-coding RNA HOX transcript antisense intergenic RNA (HOTAIR) is associated with oncogenic features in bladder cancer and is predictive of poor clinical outcomes in patients diagnosed with this disease. In this study, we evaluated the impact of the HOTAIR single nucleotide polymorphisms rs920778 and rs12826786 on bladder cancer risk and survival. This case-control study included 106 bladder cancer patients and 199 cancer-free controls. Polymorphisms were evaluated through PCR-restriction fragment length polymorphism. The odds ratio and 95% confidence intervals were tested using univariable and multivariable logistic regressions. The effects on patient survival were evaluated using the log-rank test and Cox regression models. Our data showed that the HOTAIR rs920778 and rs12826786 genetic variants are not associated with the risk of developing bladder cancer. Nevertheless, survival analyses suggested that the HOTAIR rs920778 TT genotype and rs12826786 CC genotype are associated with increased survival in male bladder cancer patients and in patients, both male and female, who have primary tumors with a pathological stage of pT2. Together, these results suggest that, despite not being associated with bladder cancer risk, HOTAIR rs920778 and rs12826786 polymorphisms might represent new prognostic factors in this type of cancer. This is particularly important as these polymorphisms might be easily evaluated in bladder cancer patients in a minimally invasive manner to better predict their clinical outcomes.
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Affiliation(s)
- Eduarda P. Martins
- Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal; (E.P.M.); (J.V.d.C.); (R.F.)
- ICVS/3B’s-PT Government Associate Laboratory, 4710-057/4805-017 Braga/Guimarães, Portugal
| | - Joana Vieira de Castro
- Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal; (E.P.M.); (J.V.d.C.); (R.F.)
- ICVS/3B’s-PT Government Associate Laboratory, 4710-057/4805-017 Braga/Guimarães, Portugal
| | - Rita Fontes
- Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal; (E.P.M.); (J.V.d.C.); (R.F.)
- ICVS/3B’s-PT Government Associate Laboratory, 4710-057/4805-017 Braga/Guimarães, Portugal
| | - Sara Monteiro-Reis
- Cancer Biology & Epigenetics Group, Research Center of IPO Porto (CI-IPOP), CI-IPOP @RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal; (S.M.-R.); (R.H.); (C.J.)
- Institute of Science and Innovation in Mechanical and Industrial Engineering (INEGI), University of Porto, 4200-465 Porto, Portugal
| | - Rui Henrique
- Cancer Biology & Epigenetics Group, Research Center of IPO Porto (CI-IPOP), CI-IPOP @RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal; (S.M.-R.); (R.H.); (C.J.)
- Department of Pathology & Molecular Immunology, ICBAS-School of Medicine & Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
- Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal
| | - Carmen Jerónimo
- Cancer Biology & Epigenetics Group, Research Center of IPO Porto (CI-IPOP), CI-IPOP @RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal; (S.M.-R.); (R.H.); (C.J.)
- Department of Pathology & Molecular Immunology, ICBAS-School of Medicine & Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
| | - Bruno M. Costa
- Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal; (E.P.M.); (J.V.d.C.); (R.F.)
- ICVS/3B’s-PT Government Associate Laboratory, 4710-057/4805-017 Braga/Guimarães, Portugal
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Anber N, Tarabay MM, Elmougy R, Abdel-Dayem MA, Elbendary EY. Association of HOTAIR gene rs920778 (C > T) and rs4759314 (A > G) polymorphism with breast cancer in Egyptian women. Mol Biol Rep 2023; 50:9153-9163. [PMID: 37776415 PMCID: PMC10635973 DOI: 10.1007/s11033-023-08725-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 07/31/2023] [Indexed: 10/02/2023]
Abstract
BACKGROUND Hox transcript antisense RNA (HOTAIR) is considered an oncogene associated with the initiation and progression of many malignancies. Previous studies have examined the connection between HOTAIR SNPs rs4759314 and rs920778 for breast cancer (BC), getting variable results in multiple ethnicities. Therefore, this study was designed to evaluate the connection between these two SNPs and disease vulnerability, clinic-laboratory, and hormonal parameters, featuring status associations with the BC risk in an Egyptian woman sample. METHODS AND RESULTS In this case-control study, DNA was taken from the blood of 100 BC patients and 100 unrelated healthy Egyptian females. The characterization of rs4759314 was genotyped using the T-ARMS-PCR method and rs920778 using the SNP-RFLP technique for all participants. The frequency of the rs4759314 A > G variation revealed a statistically significant increase in BC risk with dominant (p = 0.013, OR = 1.592, 95% Cl = 1.105-2.293), co-dominant (p = 0.006, OR = 2.314, 95%Cl = 1.278-4.191) and overdominant (p = 0.002, OR = 2.571, 95% Cl = 1.430-4.624) genetic models. On the other hand, the rs920778 C > T polymorphism was not significantly associated with BC. ER/PR positivity with HER2 negativity was significantly associated with the AA genotype compared to the AG genotype. Otherwise, no significant associations between the two SNPs and clinical stage or hormonal features could be found. In conclusion, the rs4759314 A > G SNP in the HOTAIR gene is strongly associated with BC, which might warrant its determination among affected families for prevention and early treatment.
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Affiliation(s)
- Nahla Anber
- Emergency Hospital, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
| | | | - Rehab Elmougy
- Biochemistry Division, Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt
| | - Marwa Ahmed Abdel-Dayem
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Horus University, New Damietta City, Egypt
| | - Ehab Yones Elbendary
- Clinical Nutrition Department, College of Applied Medical Sciences, Jazan University, Jazan, Kingdom of Saudi Arabia
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Tiucă RA, Tiucă OM, Pașcanu IM. The Role of Genetic Polymorphisms in Differentiated Thyroid Cancer: A 2023 Update. Biomedicines 2023; 11:biomedicines11041075. [PMID: 37189693 DOI: 10.3390/biomedicines11041075] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/24/2023] [Accepted: 03/30/2023] [Indexed: 04/05/2023] Open
Abstract
Thyroid cancer is the most common endocrine malignancy, with an increasing trend in the past decades. It has a variety of different histological subtypes, the most frequent one being differentiated thyroid cancer, which refers to papillary carcinoma, the most common histological type, followed by follicular carcinoma. Associations between genetic polymorphisms and thyroid cancer have been investigated over the years and are an intriguing topic for the scientific world. To date, the results of associations of single nucleotide polymorphisms, the most common genetic variations in the genome, with thyroid cancer have been inconsistent, but many promising results could potentially influence future research toward developing new targeted therapies and new prognostic biomarkers, thus consolidating a more personalized management for these patients. This review focuses on emphasizing the existing literature data regarding genetic polymorphisms investigated for their potential association with differentiated thyroid cancer and highlights the opportunity of using genetic variations as biomarkers of diagnosis and prognosis for thyroid cancer patients.
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Affiliation(s)
- Robert Aurelian Tiucă
- Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
- Department of Endocrinology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
- Compartment of Endocrinology, Mures County Clinical Hospital, 540139 Targu Mures, Romania
| | - Oana Mirela Tiucă
- Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
- Department of Dermatology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
- Dermatology Clinic, Mures County Clinical Hospital, 540015 Targu Mures, Romania
| | - Ionela Maria Pașcanu
- Department of Endocrinology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
- Compartment of Endocrinology, Mures County Clinical Hospital, 540139 Targu Mures, Romania
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Association of Polymorphisms within HOX Transcript Antisense RNA (HOTAIR) with Type 2 Diabetes Mellitus and Laboratory Characteristics: A Preliminary Case-Control Study. DISEASE MARKERS 2022; 2022:4327342. [PMID: 35359879 PMCID: PMC8964191 DOI: 10.1155/2022/4327342] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 03/07/2022] [Indexed: 12/14/2022]
Abstract
Type 2 diabetes mellitus (T2DM) is a complex heterogeneous disease resulting from the environment and genetic interactions. Lately, genetic association studies have shown that polymorphisms in long noncoding RNAs (lncRNAs) are associated with T2DM susceptibility. This preliminary study is aimed at investigating if HOX transcript antisense RNA (HOTAIR) polymorphisms contribute to T2DM development. Five hundred clinically diagnosed T2DM cases and 500 healthy controls were recruited from the southeast Iranian population. Genomic DNA was isolated from nucleated blood cells and genotyped for MspI (C/T) (rs920778) and AluI (A/G) (rs4759314) polymorphisms using the PCR-RFLP technique. For genotyping rs12826786 C/T and rs1899663 G/T variants, ARMS-PCR method was applied. Our findings indicated that HOTAIR rs920778 C/T, rs12826786 C/T, and rs4759314 A/G polymorphisms have a significant positive association with T2DM, while a negative association was observed between rs1899663 G/T T2DM susceptibility. Significant associations were also observed between rs920778 C/T and HDL-C as well as s4759314 A/G and both FBS and LDL-C in T2DM patients. Haplotype analysis indicated that the CGCG, CTTG, TGTA, and TTTG haplotypes of rs920778/rs1899663/rs12826786/rs4759314 significantly enhanced T2DM risk by 1.47, 1.96, 2.81, and 4.80 folds, respectively. No strong linkage disequilibrium was found between the four HOTAIR SNPs. We firstly reported that HOTAIR rs1899663 G/T, rs12826786 C/T, rs4759314 A/G, and rs920778 C/T polymorphisms might influence T2DM susceptibility by modulating different signaling pathways and could be regarded as potential prognostic markers in T2DM patients.
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Long Non-Coding RNAs at the Chromosomal Risk Loci Identified by Prostate and Breast Cancer GWAS. Genes (Basel) 2021; 12:genes12122028. [PMID: 34946977 PMCID: PMC8701176 DOI: 10.3390/genes12122028] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 12/16/2021] [Accepted: 12/17/2021] [Indexed: 12/20/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) are emerging as key players in a variety of cellular processes. Deregulation of the lncRNAs has been implicated in prostate and breast cancers. Recently, germline genetic variations associated with cancer risk have been correlated with lncRNA expression and/or function. In addition, single nucleotide polymorphisms (SNPs) at well-characterized cancer-associated lncRNAs have been analyzed for their association with cancer risk. These SNPs may occur within the lncRNA transcripts or spanning regions that may alter the structure, function, and expression of these lncRNA molecules and contribute to cancer progression and may have potential as therapeutic targets for cancer treatment. Additionally, some of these lncRNA have a tissue-specific expression profile, suggesting them as biomarkers for specific cancers. In this review, we highlight some of the cancer risk-associated SNPs that modulated lncRNAs with a potential role in prostate and breast cancers and speculate on how these lncRNAs may contribute to cancer development.
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Lampropoulou DI, Laschos K, Aravantinos G, Georgiou K, Papiris K, Theodoropoulos G, Gazouli M, Filippou D. Association between homeobox protein transcript antisense intergenic ribonucleic acid genetic polymorphisms and cholangiocarcinoma. World J Clin Cases 2021; 9:1785-1792. [PMID: 33748227 PMCID: PMC7953393 DOI: 10.12998/wjcc.v9.i8.1785] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/04/2021] [Accepted: 02/12/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Cholangiocarcinoma (CCA) represents a rare but highly aggressive malignancy that is often challenging to diagnose, especially in early stages. The role of existing tumor biomarkers for CCA diagnosis, remains controversial due to their low sensitivity and specificity. Increasing evidence has implicated long non-coding ribonucleic acid polymorphisms with cancer susceptibility in a variety of tumor types. The association between long non-coding ribonucleic acid homeobox protein transcript antisense intergenic ribonucleic acid (HOTAIR) polymorphisms and CCA risk has not been reported yet. AIM To investigate the influence of HOTAIR variants on the risk of CCA development. METHODS We conducted a case-control study in which three HOTAIR single nucleotide polymorphisms (rs920778, rs4759314 and rs7958904) were genotyped in a Greek cohort. Our study population included 122 CCA patients (80 males and 42 females) and 165 healthy controls. The polymorphisms under investigation were examined in peripheral blood samples. RESULTS HOTAIR rs4759314 AG and GG genotypes were associated with a significantly increased CCA risk [P = 0.004, odds ratio: 3.13; 95% confidence interval: 1.65-5.91 and P = 0.005, odds ratio: 12.31; 95% confidence interval: 1.48-101.87, respectively]. However, no significant associations of HOTAIR rs920778, and rs7958904 were detected. Similarly, we found no significant associations between rs4759314 AA genotype and CCA susceptibility. CONCLUSION HOTAIR rs4759314 AG and GG genotypes may be implicated with CCA development and may serve as a potential diagnostic biomarker.
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Affiliation(s)
| | - Konstantinos Laschos
- Medical Oncology, General Oncology Hospital of Kifissia “Agioi Anargiroi”, Athens 14564, Greece
| | - Gerasimos Aravantinos
- Medical Oncology, General Oncology Hospital of Kifissia “Agioi Anargiroi”, Athens 14564, Greece
| | - Konstantinos Georgiou
- 1st Department of Propaedeutic Surgery, Hippokration General Hospital of Athens, Athens Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Konstantinos Papiris
- Endoscopic Surgery Department, Hippokration General Hospital, Athens 11527, Greece
| | - George Theodoropoulos
- 1st Department of Propaedeutic Surgery, Hippokration General Hospital of Athens, Athens Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Maria Gazouli
- Basic Medical Sciences, Athens Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Dimitrios Filippou
- Anatomy and Surgical Anatomy, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
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Esmkhani S, Sadeghi H, Ghasemian M, Pirjani R, Amin-Beidokhti M, Gholami M, Yassaee F, Mirfakhraie R. Contribution of long noncoding RNA HOTAIR variants to preeclampsia susceptibility in Iranian women. Hypertens Pregnancy 2020; 40:29-35. [PMID: 33264034 DOI: 10.1080/10641955.2020.1855192] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Objective: To investigate the possible association of lncRNA HOTAIR rs920778 and rs874945 polymorphisms with preeclampsia risk in a sample from the Iranian population. Method: The study subjects included 250 preeclamptic women and 250 healthy women. The genotyping for rs920778 and rs874945 polymorphisms were performed using the TP-ARMS-PCR method. Results: HOTAIR rs920778 increased the risk of preeclampsia under the dominant and recessive inheritance patterns (OR = 4.84, 95% CI: 3.30-7.10, P < 0.0001; OR = 6.86, 95% CI: 3.51-13.42, P < 0.0001; respectively). Conclusion: This study confirmed the association of HOTAIR rs920778 polymorphism with preeclampsia in Iranian women. Further studies should be performed to confirm our findings.
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Affiliation(s)
- Sahra Esmkhani
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences , Tehran, Iran
| | - Hossein Sadeghi
- Genomic Research Center, Shahid Beheshti University of Medical Sciences , Tehran, Iran
| | - Majid Ghasemian
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran
| | - Reihaneh Pirjani
- Obstetrics and Gynecology Department, Arash Women Hospital, Tehran University of Medical Sciences , Tehran, Iran
| | - Mona Amin-Beidokhti
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran
| | - Milad Gholami
- Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences , Arak, Iran
| | - Fakhrolmolouk Yassaee
- Department of Obstetrics and Gynecology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences , Tehran, Iran
| | - Reza Mirfakhraie
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran
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Shavali M, Pouladi N, Abdolahi S, Farajzadeh D, Moniri S. Investigating the association of rs920778T > C polymorphism in HOTAIR gene in breast cancer patients in the northwestern of Iran. Meta Gene 2020. [DOI: 10.1016/j.mgene.2020.100756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Rajagopal T, Seshachalam A, Akshaya RL, Rathnam KK, Talluri S, Jothi A, Dunna NR. Association of HOTAIR (rs920778 and rs1899663) and NME1 (rs16949649 and rs2302254) gene polymorphisms with breast cancer risk in India. Gene 2020; 762:145033. [PMID: 32781191 DOI: 10.1016/j.gene.2020.145033] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/20/2020] [Accepted: 08/04/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Until now, no study has reported the combined effect of genetic variants of HOTAIR and NME1 towards breast cancer (BC) pathogenesis. Hence, the aim of the present study is to determine the risk of breast cancer development with HOTAIR (rs920778 C > T and rs1899663 G > T) and NME1 (rs16949649 T > C and rs2302254 C > T) genetic polymorphisms in the Indian population for the first time. MATERIALS AND METHODS To investigate the genetic association of these four SNPs, we conducted a population-based case-control study involving 1011 subjects (502 histologically confirmed BC patients and 509 disease-free controls) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS HOTAIR rs920778 TC genotype elevated the risk of BC (OR = 1.39, 95% CI = 1.06-1.83, p = 0.018) and individuals carrying the mutant allele (T) of rs1899663 had increased BC risk (OR = 1.23, 95% CI = 1.02-1.47, p = 0.026). The presence of the NME1 rs16949649 CC genotype increased the risk of BC (OR = 1.76, 95% CI = 1.15-2.71, p = 0.009). Moreover, the HOTAIR rs920778 variant (TC + CC) increased the risk of BC in pre-menopausal women (OR = 5.86; p < 0.0001). Women carrying 2 or 3 mutant alleles for the investigated SNPs were observed to have an elevated risk of BC. CONCLUSION The results of the present study highlight the presence of significant associations between NME1 rs16949649 and HOTAIR (rs920778 and rs1899663) polymorphisms and breast cancer development in Indian women.
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Affiliation(s)
- Taruna Rajagopal
- Cancer Genomics Laboratory, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, India
| | - Arun Seshachalam
- Department of Medical and Paediatric Oncology, Dr.G.V.N Cancer Institute, Trichy, India
| | - R L Akshaya
- Cancer Genomics Laboratory, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, India
| | - Krishna Kumar Rathnam
- Department of Hemato Oncology - Medical Oncology and Bone Marrow Transplantation, Meenakshi Mission Hospital & Research Centre, Madurai, India
| | - Srikanth Talluri
- Dana Farber Cancer Institute, Boston, MA, USA; Veterans Administration Boston Healthcare System, West Roxbury, MA, USA
| | - Arunachalam Jothi
- Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, India
| | - Nageswara Rao Dunna
- Cancer Genomics Laboratory, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, India.
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Liu X, Zhao Y, Li Y, Lin F, Zhang J. Association between HOTAIR genetic polymorphisms and cancer susceptibility: A meta-analysis involving 122,832 subjects. Genomics 2020; 112:3036-3055. [PMID: 32454167 DOI: 10.1016/j.ygeno.2020.05.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 05/17/2020] [Accepted: 05/19/2020] [Indexed: 01/30/2023]
Abstract
The association between polymorphisms in HOTAIR gene and cancer susceptibility has been analyzed intensively, but the conclusions are inconsistent. Therefore, we carried out a meta-analysis aiming to assess the relationship exactly. Eligible studies were searched in PubMed and Embase databases up to October 31, 2019. Odds ratios with 95% confidence intervals were used to assess the strength of association. Sensitivity analysis and publication bias were applied to evaluate the reliability of the study. Moreover, TSA was conducted to estimate the robustness of the results. Totally, 116 studies involving 122,832 subjects were analyzed in our meta-analysis. Significant increased risk of cancer was detected for the rs4759314, rs920778, rs1899663, rs12826786 and rs874945 polymorphisms. Further subgroup analyses according to cancer type revealed that different polymorphisms were associated with the risk of specific type of cancer. For example, the rs4759314 polymorphism was significantly associated with the risk of estrogen-dependent cancer, whereas the rs920778 polymorphism was associated with the risk of gastrointestinal cancer. In conclusion, our findings indicated that the rs4759314, rs920778, rs1899663, rs12826786 and rs874945 polymorphisms in HOTAIR may serve as genetic biomarkers of cancer.
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Affiliation(s)
- Xu Liu
- Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China
| | - Yating Zhao
- Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China
| | - Ying Li
- Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China; Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China
| | - Fengzhan Lin
- Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China; Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China
| | - Jian Zhang
- Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China; Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China.
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Tian Y, Lin X, Yang F, Zhao J, Yao K, Bian C. Contribution of xeroderma pigmentosum complementation group D gene polymorphisms in breast and ovarian cancer susceptibility: A protocol for systematic review and meta analysis. Medicine (Baltimore) 2020; 99:e20299. [PMID: 32481313 PMCID: PMC7249878 DOI: 10.1097/md.0000000000020299] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 03/29/2020] [Accepted: 04/16/2020] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND The role of xeroderma pigmentosum complementation group D (XPD) gene polymorphisms in breast and ovarian cancer development has long been controversial and existing data were inconsistent. Here, we conducted a comprehensive systemic review and meta-analysis to better clarify the association. METHODS Relevant case-control studies published in electronic data base from October 1999 to September 2019 were assessed. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (95%CIs) were calculated by using Revman 5.2 software (Cochrane Collaboration, Copenhagen). RESULTS 31 articles including 38 case-control studies and 2 XPD polymorphisms (rs1799793 and rs238406) were analyzed. The results showed statistical significance in heterozygous mutants among Asian population for rs1799793 (GA vs GG + AA: OR = 1.38, 95%CI = 1.21-1.56), and Caucasian population for rs238406 (CA vs AA + CC: OR = 0.63, 95%CI = 0.49-0.80), while the rest comparisons including overall groups and subgroups stratified by cancer types and ethnicity failed to indicate any association with breast and ovarian cancer risk. CONCLUSIONS The current meta-analysis suggested no concrete correlation of XPD rs1799793(G/A) and rs238406(C/A) polymorphisms with breast cancer or ovarian cancer susceptibility. However, it indicated that heterozygous genotypes might share different pathophysiologic mechanism from not only homozygous wildtypes but also homozygous mutants. More case-control studies with well-adjusted data and diverse populations are essential for validation of our conclusion.
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Affiliation(s)
| | | | | | | | - Kui Yao
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, P R China
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Rajagopal T, Talluri S, Akshaya R, Dunna NR. HOTAIR LncRNA: A novel oncogenic propellant in human cancer. Clin Chim Acta 2020; 503:1-18. [DOI: 10.1016/j.cca.2019.12.028] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 12/27/2019] [Accepted: 12/30/2019] [Indexed: 02/08/2023]
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Rakhshan A, Zarrinpour N, Moradi A, Ahadi M, Omrani MD, Ghafouri-Fard S, Taheri M. A single nucleotide polymorphism within HOX Transcript Antisense RNA (HOTAIR) is associated with risk of psoriasis. Int J Immunogenet 2020; 47:430-434. [PMID: 32090437 DOI: 10.1111/iji.12482] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Revised: 01/22/2020] [Accepted: 02/10/2020] [Indexed: 12/13/2022]
Abstract
Recent studies have shown participation of long non-coding RNAs (lncRNAs) in the pathogenesis of psoriasis. Several mechanisms might be involved in the dysregulation of expression of lncRNAs in patients with psoriasis, among them is the presence of single nucleotide polymorphisms (SNPs) which modulate expression or function of these transcripts. In the present work, we genotyped three SNPs (rs12826786, rs1899663 and rs4759314) of the HOX Transcript Antisense RNA (HOTAIR) in 286 patients with psoriasis and 300 control subjects. The rs12826786 was associated with risk of psoriasis in dominant model (TC + TT vs. CC: OR (95% CI) = 1.59 (0.1.14-2.22), adjusted p-value = .02). In the allelic model, T allele of this SNP significantly increased the risk of psoriasis compared with the C allele (OR (95% CI) = 1.35 (1.06-1.71), adjusted p-value = .04). Other SNPs were not associated with risk of psoriasis in any inheritance model. No significant difference was found in haplotype frequencies between cases and controls. The current work shows association between a genomic variant within HOTAIR and risk of psoriasis. The clinical significance of this finding should be assessed in future studies.
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Affiliation(s)
- Azadeh Rakhshan
- Department of Pathology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nader Zarrinpour
- Center for Research and Training in Skin Disease and Leprosy, Tehran University of Medical Sciences, Tehran, Iran
| | - Afshin Moradi
- Cancer Research Center, Faculty of Medicine, Shohada Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Mahsa Ahadi
- Cancer Research Center, Faculty of Medicine, Shohada Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Mir Davood Omrani
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Minn AKK, Sato N, Mieno MN, Arai T, Muramatsu M. Association study of long non-coding RNA HOTAIR rs920778 polymorphism with the risk of cancer in an elderly Japanese population. Gene 2019; 729:144263. [PMID: 31759985 DOI: 10.1016/j.gene.2019.144263] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 11/07/2019] [Accepted: 11/08/2019] [Indexed: 02/07/2023]
Abstract
The HOTAIR gene encodes a long noncoding RNA (lncRNA), which functions in development and tumorigenesis. A single nucleotide polymorphism (SNP) rs920778 in the HOTAIR gene, has been recurrently studied for susceptibility to many cancers including oesophageal cancer, gastric cancer, lung cancer, and hepatocellular carcinoma. Most of these studies were conducted in Chinese populations, and a few in Turkish, Iranian, and Portuguese populations. They mostly give rise to controversial results. It still remains largely unknown whether the cancer risk is conferred in a Japanese population. Here, we established an association study on the representative SNP rs920778, to examine its contribution to the presence of cancer in consecutive autopsy cases in the JG-SNP database. A total of 1373 subjects (mean age 80) including 827 cancer positive and 546 cancer negative subjects were analyzed. As a result, the occurrence of overall cancer was not associated with the rs920778 polymorphism (p > 0.05). For each cancer type, we did not find association except for lung cancer (p = 0.04) which was more likely a by-chance association after multiple testing. Our findings imply that rs920778 polymorphism does not affect total cancer presence and the effect on specific cancer types is also weak in the Japanese population.
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Affiliation(s)
- Aye Ko Ko Minn
- Department of Molecular Epidemiology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan.
| | - Noriko Sato
- Department of Molecular Epidemiology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan
| | | | - Tomio Arai
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
| | - Masaaki Muramatsu
- Department of Molecular Epidemiology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan
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Association of HOTAIR gene polymorphisms and haplotypes with uterine leiomyoma susceptibility in southeast of Iran. Mol Biol Rep 2019; 46:4271-4277. [PMID: 31119441 DOI: 10.1007/s11033-019-04881-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 04/27/2019] [Indexed: 12/12/2022]
Abstract
Uterine leiomyoma (UL) is the most common benign tumor of the uterus. HOX transcript antisense RNA (HOTAIR) as a lncRNAs is the product of HOXC gene that plays a major role in the invasion and development of different tumors. Several lines of evidence have been suggested the effects of HOTAIR polymorphisms on cancer risk. The aim of the present study was to analyze the effects of HOTAIR polymorphisms (rs12826786, rs920778, rs4759314 and rs1899663) on UL in southeast of Iran. A total of 152 women with UL and 182 age-matched healthy women were selected in the case-control study. The PCR-RFLP and ARMS-PCR methods were used for genotyping. HOTAIR rs920778 polymorphism was associated with a lower risk of UL in dominant [OR, 0.5 (95% CI, 0.3-0.9); P = 0.03], recessive [OR, 0.6 (95% CI, 0.4-0.9; P = 0.016] and allelic models [OR, 0.6(95% CI, 0.5-0.9); P = 0.004]. However, HOTAIR rs12826786 polymorphism was associated with a higher risk of UL in dominant [OR, 2.6 (95% CI, 1.6-4.1); P = 0.0001], recessive [OR, 1.9 (95% CI, 1-3.6); P = 0.04] and allelic models [OR, 1.8 (95% CI, 1.3-2.4); P = 0.0003]. There was no association between HOTAIR rs4759314 and rs1899663 polymorphisms and UL susceptibility. The frequency of CTGA haplotype was lower in UL women; however, the CCGA, TCGA, TTTA, and TTGA haplotypes were more frequent in UL women. Our results indicated that HOTAIR rs12826786 and rs920778 polymorphisms had a significant effect on UL susceptibility. The HOTAIR haplotypes could affect UL susceptibility.
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Yang F, Mu X, Bian C, Zhang H, Yi T, Zhao X, Lin X. Association of excision repair cross-complimentary group 1 gene polymorphisms with breast and ovarian cancer susceptibility. J Cell Biochem 2019; 120:15635-15647. [PMID: 31081240 DOI: 10.1002/jcb.28830] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 02/20/2019] [Accepted: 02/28/2019] [Indexed: 12/13/2022]
Abstract
The role of excision repair cross-complimentary group 1 (ERCC1) gene polymorphisms in breast and ovarian cancer development has long been controversial and existing data were inconsistent. Here, we conducted a comprehensive meta-analysis to better clarify the association. Case-control studies published from December 2008 to November 2018 were assessed. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. Fifteen articles with 24 case-control studies and 3 ERCC1 polymorphisms were enrolled. A total of 20 923 participants including 9896 cases and 11 027 controls were analyzed. The results showed that C to T variation in the ERCC1 rs11615 (C/T) polymorphisms was correlated with breast cancer susceptibility (T vs C: OR = 1.19, 95% CI = 1.02-1.38; TT + CT vs CC: OR = 1.24, 95% CI = 1.12-1.36). ERCC1 rs3212986 (C/A) polymorphisms posed an increased risk for breast and ovarian cancer as whole (A vs C: OR = 1.12, 95% CI = 1.01-1.25; AA + CA vs CC: OR = 1.11, 95% CI = 1.02-1.22), and presented especially higher risk for ovarian cancer (A vs C: OR = 1.31, 95% CI = 1.05-1.63; AA vs CA + CC: OR = 1.66, 95% CI = 1.12-2.47; AA vs CC: OR = 1.72, 95% CI = 1.12-2.64). Meanwhile, neither overall group analyses nor stratified analyses displayed any association of ERCC1 rs2298881 (A/C) polymorphisms in breast and ovarian cancer susceptibility. This meta-analysis suggested that ERCC1 rs11615 (C/T) polymorphisms were associated with breast cancer susceptibility and rs3212986 (C/A) polymorphisms were especially correlated with ovarian cancer risk. More case-control studies with well-adjusted data and diverse populations are essential for validation of our conclusion.
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Affiliation(s)
- Fan Yang
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, P R China
| | - Xiyan Mu
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, P R China
| | - Ce Bian
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, P R China
| | - Huan Zhang
- Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, P R China
| | - Tao Yi
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, P R China
| | - Xia Zhao
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, P R China
| | - Xiaojuan Lin
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, P R China
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The association of FOXP3 gene polymorphisms with cancer susceptibility: a comprehensive systemic review and meta-analysis. Biosci Rep 2019; 39:BSR20181809. [PMID: 30782783 PMCID: PMC6422890 DOI: 10.1042/bsr20181809] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 02/11/2019] [Accepted: 02/18/2019] [Indexed: 12/12/2022] Open
Abstract
The role of forkhead box P3 (FOXP3) protein in tumorigenesis has long been controversial and existing data on the association between FOXP3 gene polymorphisms and cancer susceptibility were inconsistent. Here, we conducted a meta-analysis to better clarify the relationship. A comprehensive search of studies published from July 2008 to June 2018 was conducted. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs) were performed using the Revman 5.2 software. A total of 12 articles with 19 case–control studies and 10389 participants were included. Three FOXP3 polymorphisms and six cancer types were evaluated. While no significant results were observed in overall and breast cancer groups for rs3761548 (A/C) polymorphisms, the pooled data showed an elevated risk of cancer in variant AA genotypes and A allele for Chinese population (AA vs. AC+CC: OR = 1.61, 95% CI = 1.09, 2.39; AA vs. CC: OR = 1.74, 95% CI = 1.05, 2.89; A vs. C: OR = 1.34, 95% CI = 1.00, 1.78). Neither the overall group analyses nor the subgroup analyses stratified by cancer type and ethnicity proposed any significant association of rs2280883 (C/T) and rs3761549 (T/C) polymorphisms with cancer susceptibility. This meta-analysis suggested that FOXP3 rs3761548 (A/C) polymorphisms were associated with increased cancer risk in Chinese population while rs2280883 (C/T) and rs3761549 (T/C) polymorphisms were not. More large-sample researches with diverse ethnicities and cancer types are needed to draw a concrete conclusion.
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Jiang D, Xu L, Ni J, Zhang J, Cai M, Shen L. Functional polymorphisms in LncRNA HOTAIR contribute to susceptibility of pancreatic cancer. Cancer Cell Int 2019; 19:47. [PMID: 30867650 PMCID: PMC6396528 DOI: 10.1186/s12935-019-0761-x] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2018] [Accepted: 02/15/2019] [Indexed: 12/15/2022] Open
Abstract
Background Pancreatic cancer (PC) remains one of the most aggressive cancers worldwide. However, genetic factors underlying PC susceptibility remain largely unclear. Long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) acts as an oncogene and its genetic variation has been linked to many cancers. However, the associations between genetic variants in HOTAIR gene and PC risk has not yet been reported. Methods A two-stage, case–control study was conducted to investigate the associations between HOTAIR SNPs and the PC risk. Dual luciferase reporter assay and real-time -PCR (RT-PCR) was conducted to evaluate the potential regulatory function of HOTAIR rs4759314 and rs200349340. Results We found the minor alleles of rs4759314 (OR = 1.76; 95 CI 1.37–2.25; P = 0.001) and rs200349340 (OR = 1.32; 95 CI 1.12–1.56; P = 0.001) were significantly associated with PC susceptibility. In functional experiments, we found subjects carrying the minor alleles of rs4759314 and rs200349340 had significantly higher HOTAIR RNA levels (mean ± SD) than those carrying the major alleles in PC tissues. For rs4759314, cells transfected with rs4759314 -G allele construct showed higher relative luciferase activity; while for rs200349340, cells transfected with rs200349340 -G allele construct showed more sensitive change of the relative luciferase activity. Conclusion Our studies revealed that functional SNP rs4759314 and rs200349340 of HOTAIR had strong associations with PC susceptibility. These findings elucidate that functional genetic variants influencing lncRNA expression may explain a portion of PC genetic basis. Electronic supplementary material The online version of this article (10.1186/s12935-019-0761-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Dawei Jiang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jiaxing University, No. 1882 Zhonghuan South Road, Jiaxing, 314001 Zhejiang People's Republic of China
| | - Liu Xu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jiaxing University, No. 1882 Zhonghuan South Road, Jiaxing, 314001 Zhejiang People's Republic of China
| | - Jianqi Ni
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jiaxing University, No. 1882 Zhonghuan South Road, Jiaxing, 314001 Zhejiang People's Republic of China
| | - Jie Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jiaxing University, No. 1882 Zhonghuan South Road, Jiaxing, 314001 Zhejiang People's Republic of China
| | - Min Cai
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jiaxing University, No. 1882 Zhonghuan South Road, Jiaxing, 314001 Zhejiang People's Republic of China
| | - Lan Shen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jiaxing University, No. 1882 Zhonghuan South Road, Jiaxing, 314001 Zhejiang People's Republic of China
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Jiang D, Li H, Xiang H, Gao M, Yin C, Wang H, Sun Y, Xiong M. Long Chain Non-Coding RNA (lncRNA) HOTAIR Knockdown Increases miR-454-3p to Suppress Gastric Cancer Growth by Targeting STAT3/Cyclin D1. Med Sci Monit 2019; 25:1537-1548. [PMID: 30810117 PMCID: PMC6402277 DOI: 10.12659/msm.913087] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Gastric cancer is a common gastrointestinal tumor. The incidence and mortality of gastric cancer are very high. Therefore, it is important to study targeted drugs. Recent studies found long chain non-coding RNA (lncRNAs) and microRNAs (miRNAs) were abnormal in gastric cancer. MATERIAL AND METHODS We collected adjacent normal and cancer tissues of gastric cancer patients and measured HOTAIR, miR-454-3p, STAT3, and Cyclin D1 expression and analyzed the correlation with clinical status. We also measured AGS and SGC7901 cells proliferation rate of different groups by MTT assay, and we evaluated AGS and SGC7901 cell apoptosis and cell cycle by flow cytometry. In addition, we assessed the relative proteins expressions by WB assay. Finally, we explored the correlation between miR-454-3p and STAT3 by use of double luciferase reporter. RESULTS lncRNA HOTAIR was negatively correlated with miR-454-3p expression in gastric cancer tissues. lncRNA HOTAIR knockdown suppressed AGS and SGC7901, which are gastric cancer cell lines that promote cell proliferation by increasing cell apoptosis and keeping the cell cycle in G1 phase. In further mechanism research, we found that the STAT3 and Cyclin D1 proteins expressions were suppressed by lncRNA HOTAIR down-regulation in AGS and SGC7901 cells. CONCLUSIONS Our results suggest that lncRNA HOTAIR knockdown stimulates miR-454-3p expression to inhibit gastric cancer growth by depressing STAT3/Cyclin D1 activity.
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Affiliation(s)
- Datong Jiang
- Department of Emergency Surgery, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland)
| | - He Li
- Department of Emergency Surgery, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland)
| | - Heping Xiang
- Department of Emergency Surgery, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland)
| | - Ming Gao
- Department of Emergency Surgery, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland)
| | - Chunlin Yin
- Department of Emergency Surgery, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland)
| | - Haiping Wang
- Department of Emergency Surgery, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland)
| | - Yuansong Sun
- Department of Emergency Surgery, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland)
| | - Maoming Xiong
- Department of Gastroenterological Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland)
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Tung MC, Wen YC, Wang SS, Lin YW, Chow JM, Yang SF, Chien MH. Impact of Long Non-Coding RNA HOTAIR Genetic Variants on the Susceptibility and Clinicopathologic Characteristics of Patients with Urothelial Cell Carcinoma. J Clin Med 2019; 8:jcm8030282. [PMID: 30813594 PMCID: PMC6462928 DOI: 10.3390/jcm8030282] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 02/19/2019] [Accepted: 02/22/2019] [Indexed: 12/20/2022] Open
Abstract
Increasing evidence shows that dysregulated expression of long non-coding (lnc)RNAs can serve as diagnostic or prognostic markers in urothelial cell carcinoma (UCC), the most common pathological type of bladder cancer. lncRNA HOX transcript antisense RNA (HOTAIR) was shown to promote tumor progression and be associated with a poor prognosis in multiple cancers including bladder cancer. Polymorphisms of HOTAIR were recently linked to a predisposition for diverse malignancies. Herein we conducted a case-control study to evaluate whether genetic polymorphisms of HOTAIR were associated with UCC risk and clinicopathologic characteristics. Four loci (rs920778 T>C, rs1899663 G>T, rs4759314 A>G, and rs12427129, C>T) of HOTAIR were genotyped by a TaqMan allelic discrimination method in 431 cases and 862 controls. We found that female patients who carried AG + GG genotype of rs4759314 were associated with an increased UCC risk after controlling for age and tobacco consumption (adjusted odds ratio (AOR) = 1.92, 95% confidence interval (CI): 1.01–3.64, p = 0.047) and a lower overall survival rate (p = 0.008). Moreover, patients with a smoking habit or younger age (≤65 years), who had at least one T allele of HOTAIR rs12427129 were at a higher risk of developing advance tumor T satge (p = 0.046), compared to those patients with CC homozygotes. In contrast, rs920778 C allele carriers were negatively correlated with the development of lymph node metastasis (OR = 0.51, 95% CI: 0.28–0.94, p = 0.031). Further analyses of clinical datasets revealed correlations of the expression of HOTAIR with tumor metastasis and a poor survival rate in patients with UCC. Our results verified the diverse impacts of HOTAIR variants on UCC susceptibility and clinicopathologic characteristics.
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Affiliation(s)
- Min-Che Tung
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
- Department of Surgery, Tungs' Taichung Metro Harbor Hospital, Taichung 43304, Taiwan.
| | - Yu-Ching Wen
- Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan.
- Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
| | - Shian-Shiang Wang
- Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 00407, Taiwan.
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
| | - Yung-Wei Lin
- Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan.
- Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
| | - Jyh-Ming Chow
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan.
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
| | - Ming-Hsien Chien
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
- Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei 40201, Taiwan.
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Lampropoulou DI, Aravantinos G, Katifelis H, Lazaris F, Laschos K, Theodosopoulos T, Papadimitriou C, Gazouli M. Long non-coding RNA polymorphisms and prediction of response to chemotherapy based on irinotecan in patients with metastatic colorectal cancer. Cancer Biomark 2019; 25:213-221. [PMID: 31045514 DOI: 10.3233/cbm-182383] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Colorectal cancer is the fourth cause of cancer related death. Drug resistance and toxicity remain major clinical issues. HOTAIR and MALAT1 are long non-coding RNAS that affect cellular proliferation, apoptosis and drug resistance; their up-regulation has been linked with a poor prognosis. OBJECTIVE Investigation of the association between rs4759314 HOTAIR and rs3200401 MALAT1 polymorphisms and irinotecan-based chemotherapy in terms of drug efficacy and toxicity. METHODS Samples from 98 patients receiving different regimens of irinotecan-based therapy were included. Efficacy and toxicity were evaluated. KRAS mutation, rs3200401 HOTAIR and rs4759314 MALAT1 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR. RESULTS Neither rs3200401 MALAT1 nor rs4759314 HOTAIR polymorphism are associated with response to treatment regimens. Rs4759314 was also not associated with increased toxicity in patients receiving irinotecan-based regimens. CT genotype of rs3200401 was associated with significantly reduced overall survival. An association between KRAS mutation and AG/GG genotypes in the rs4759314 was detected. CONCLUSIONS CT genotype of rs3200401 MALAT1 polymorphism could serve as a toxicity biomarker. Carriers of the G allele of the rs4759314 HOTAIR are more likely to be carriers of KRAS mutations too. However, further studies in larger patient populations are required.
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Affiliation(s)
| | - Gerasimos Aravantinos
- Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece
| | - Hector Katifelis
- Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Foivos Lazaris
- Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Konstantinos Laschos
- Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece
| | - Theodosios Theodosopoulos
- Second Department of Surgery, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Christos Papadimitriou
- Second Department of Surgery, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Gazouli
- Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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