HOTAIR genetic variants are associated with prostate cancer and benign prostate hyperplasia in an Iranian population

Taheri, Mohammad; Habibi, Mohsen; Noroozi, Rezvan; Rakhshan, Azadeh; Sarrafzadeh, Shaghayegh; Sayad, Arezou; Ghafouri‐Fard, Soudeh

doi:10.1016/j.gene.2017.02.031

Cited by 61 publications

(46 citation statements)

References 20 publications

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“…Interestingly, one study demonstrated the association of HOTAIR polymorphisms and genetic variants with PCa. In the study, 3 HOTAIR polymorphisms (rs12826786, rs1899663, and rs4759314) were associated with the risk of PCa [20]. Whether this risk referred to a risk locus for the occurrence and development of PCa remained inconclusive.…”

Section: Hotair In Prostate Cancermentioning

confidence: 94%

“…Aberrantly increased HOTAIR expression has been detected in several tumors, and HOTAIR expression has been positively correlated with initiation, growth, angiogenesis, progression, drug resistance, recurrence, and poor prognosis by regulating several downstream targets via multiple signaling pathways in cancer [11][12][13][14][15] (Table 1). Polymorphisms of lncRNAs, including HOTAIR polymophisms, have been associated with the risk and susceptibility of the occurrence and development of human cancer; whether this is a potentially predictive and therapeutic biomarker remains undetermined [16][17][18][19][20]. Thus, lncRNAs, including HOTAIR, drive important cancer phenotypes by their interactions with other cellular macromolecules, including DNA, protein, and RNA.…”

Section: Reviewmentioning

confidence: 99%

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HOTAIR: An Oncogenic Long Non-Coding RNA in Human Cancer

Tang

Hann

2018

Cell Physiol Biochem

206

130

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Long non-coding RNAs (LncRNAs) represent a novel class of noncoding RNAs that are longer than 200 nucleotides without protein-coding potential and function as novel master regulators in various human diseases, including cancer. Accumulating evidence shows that lncRNAs are dysregulated and implicated in various aspects of cellular homeostasis, such as proliferation, apoptosis, mobility, invasion, metastasis, chromatin remodeling, gene transcription, and post-transcriptional processing. However, the mechanisms by which lncRNAs regulate various biological functions in human diseases have yet to be determined. HOX antisense intergenic RNA (HOTAIR) is a recently discovered lncRNA and plays a critical role in various areas of cancer, such as proliferation, survival, migration, drug resistance, and genomic stability. In this review, we briefly introduce the concept, identification, and biological functions of HOTAIR. We then describe the involvement of HOTAIR that has been associated with tumorigenesis, growth, invasion, cancer stem cell differentiation, metastasis, and drug resistance in cancer. We also discuss emerging insights into the role of HOTAIR as potential biomarkers and therapeutic targets for novel treatment paradigms in cancer.

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Section: Hotair In Prostate Cancermentioning

confidence: 94%

Section: Reviewmentioning

confidence: 99%

HOTAIR: An Oncogenic Long Non-Coding RNA in Human Cancer

Tang

Hann

2018

Cell Physiol Biochem

206

130

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“…15,16 Several studies investigated the impact of HOTAIR gene polymorphisms on the incidence risk of various cancers including BC, gastric cancer, prostate cancer, and ovarian cancer. [17][18][19][20][21][22][23][24][25] However, the data from these studies remain controversial and inconclusive. Furthermore, few studies have been conducted regarding the association of HOTAIR gene polymorphisms on BC risk.…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms of HOTAIR gene are associated with the risk of breast cancer in a sample of southeast Iranian population

et al. 2017

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There is an increasing body of evidence which highlights the critical functions of long non-coding RNAs in the carcinogenicity mechanism of a variety of cancers. It has been reported that HOX transcript antisense intergenic RNA, a member of long non-coding RNA family, increases breast cancer risk. To date, no data regarding the association between HOX transcript antisense intergenic RNA polymorphisms and the risk of breast cancer development has been reported in Iran. Here, we examine the possible association between HOX transcript antisense intergenic RNA gene polymorphisms and breast cancer in a sample of southeast Iranian female population. The HOX transcript antisense intergenic RNA rs920778, rs12826786, rs4759314, and 1899663 gene polymorphisms were genotyped in 220 cases and 231 controls by polymerase chain reaction-restriction fragment length polymorphism. Our findings indicated that rs920778 polymorphism has significant positive association with breast cancer; rs12826786 and rs1899663 polymorphisms demonstrated significant negative association with breast cancer; and the rs4759314 variant was not associated with breast cancer risk. Haplotype analysis revealed that TGAC, CTAT, and TTAT haplotypes significantly decreased the risk of breast cancer compared with rs920778T/rs1899663G/rs4759314A/rs12826786T haplotype. In conclusion, we investigated only four variants of HOX transcript antisense intergenic RNA gene, and the findings suggest that HOX transcript antisense intergenic RNA rs920778, rs12826786, and rs1899663 polymorphisms may be associated with breast cancer risk in a sample of southeast Iranian population. Further replication studies with other polymorphisms of HOX transcript antisense intergenic RNA gene involving a greater sample size and different ethnicities are necessary to verify our findings.

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“…In addition, HOTAIR has been shown to contribute to prostate cancer risk. A recent study demonstrated the association between HOTAIR polymorphisms (rs12826786, rs1899663, and rs4759314) and risk of prostate cancer in patients with prostate cancer, suggesting that HOTAIR is a risk locus for prostate cancer [22]. Thus, HOTAIR can be regarded as a potential independent prognostic biomarker and a potential therapeutic target for treatment of prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Crosstalk of NF-κB/P65 and LncRNA HOTAIR-Mediated Repression of MUC1 Expression Contribute to Synergistic Inhibition of Castration-Resistant Prostate Cancer by Polyphyllin 1–Enzalutamide Combination Treatment

Xiang

Zou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Polyphyllin I (PPI), one of the steroidal saponins in Paris polyphylla, reportedly exhibits antitumor effects. However, the detailed mechanism underlying PPI, particularly in enhancing the effect of the androgen receptor inhibitor enzalutamide in controlling castration-resistant prostate cancer (CRPC) has not been explored. Methods: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) expression was measured by quantitative real time-PCR (qRT-PCR). Western blot analysis was performed to determine the protein expression levels of MUC1, p65, and p50. Silencing of HOTAIR was evaluated using the siRNA procedure. The promoter activity of the MUC1 gene was determined using Secrete-Pair Dual Luminescence Assay Kit. Exogenous expression of HOTAIR, p65, and MUC1 was conducted by transient transfection assay. A xenograft tumor model in nude mice was used to further evaluate the effect of the combination of PPI and enzalutamide in vivo. Results: We showed that PPI significantly inhibited growth and induced cell cycle arrest in CRPC cells. PPI also decreased p65 and MUC1 protein expression and reduced HOTAIR expression. Exogenously expressed p65 resisted the PPI-inhibited expression of HOTAIR, whereas silenced HOTAIR reduced MUC1 protein but exerted no effect on the expression of p65 and p50 proteins. Conversely, exogenously expressed HOTAIR resisted the PPI-inhibited MUC1 protein expression, and excessive expression of MUC1 antagonized the PPI-inhibited cell growth. Notably, PPI combined with enzalutamide exerted a synergistic effect. Consistent with this finding, PPI inhibited tumor growth, HOTAIR expression, as well as p65 and MUC1 protein expressions in vivo. Conclusions: Our results indicate that PPI inhibits the growth of CRPC cells by inhibiting p65 protein and concomitantly reducing HOTAIR expression, thereby suppressing MUC1 gene expression. The novel regulatory interaction of p65 and HOTAIR converge in the inhibition of MUC1 expression and overall PPI response. The combination of PPI and enzalutamide exhibits synergy. This study reveals a novel mechanism underlying the synergistic inhibitory effect of PPI and enzalutamide on the growth of CRPC cells.

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HOTAIR genetic variants are associated with prostate cancer and benign prostate hyperplasia in an Iranian population

Cited by 61 publications

References 20 publications

HOTAIR: An Oncogenic Long Non-Coding RNA in Human Cancer

HOTAIR: An Oncogenic Long Non-Coding RNA in Human Cancer

Genetic polymorphisms of HOTAIR gene are associated with the risk of breast cancer in a sample of southeast Iranian population

Crosstalk of NF-κB/P65 and LncRNA HOTAIR-Mediated Repression of MUC1 Expression Contribute to Synergistic Inhibition of Castration-Resistant Prostate Cancer by Polyphyllin 1–Enzalutamide Combination Treatment

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