HOTAIR lncRNA SNPs rs920778 and rs1899663 are associated with smoking, male gender, and squamous cell carcinoma in a Chinese lung cancer population

Wang, Cong; Li, Ying; Li, Yongwen; Zhang, Hongbing; Gong, Hao; Yin, Yuan; Li, Wei-ting; Liu, Hongyu; Chen, Jun

doi:10.1038/s41401-018-0083-x

Cited by 34 publications

(30 citation statements)

References 34 publications

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“…Cancer patients with these three cancer types who harbored the HOTAIR rs920778T allele were significantly associated with an elevated risk or an advanced TNM stage of these cancers compared to those with the C allele in a Chinese population [27,28,29]. Recently, gene polymorphisms in rs920778 were also found to significantly increase one’s susceptibility to lung cancer in a Chinese lung cancer population [24]. About the analysis stratified by ethnicity, there is a meta-analysis which showed that a significant association between rs920778 SNPs and cancer susceptibility was observed in Asians under dominant, recessive, homozygous, and heterozygous models.…”

Section: Discussionmentioning

confidence: 99%

“…Total DNA was extracted from peripheral blood of each participant using a QIAamp DNA Blood Mini Kit (Qiagen, Valencia, CA, USA) according to the manufacturer’s protocols. In total, four intronic SNPs of HOX transcript antisense RNA ( HOTAIR ) (rs920778 T>C, rs1899663 G>T, rs4759314 A>G, and rs12427129 C>T) were chosen in this study based on the International HapMap Project and previous studies [23,24,25,26]. These four HOTAIR SNPs were selected due to these SNPs being well-defined, and have been widely evaluated in their association with cancer susceptibility in a broad range of cancers such as oral, lung, cervical, and liver cancers in the Han Chinese population from Taiwan and Mainland China [23,24,26,27].…”

Section: Methodsmentioning

confidence: 99%

“…However, the effects of HOTAIR gene polymorphisms on the risk of UCC remain unexplored. Accordingly, we selected four intronic SNPs (rs920778, rs1899663, rs4759314, and rs12427129) which were recently identified to be associated with cancer risk or development [23,24] and conducted the present case-control study which included 431 UCC patients and 862 healthy controls, in an attempt to investigate the roles of HOTAIR SNPs in the risk and clinical characteristics of UCC in a Taiwanese population.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Impact of Long Non-Coding RNA HOTAIR Genetic Variants on the Susceptibility and Clinicopathologic Characteristics of Patients with Urothelial Cell Carcinoma

Tung

Wen

Wang

et al. 2019

JCM

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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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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of Long Non-Coding RNA HOTAIR Genetic Variants on the Susceptibility and Clinicopathologic Characteristics of Patients with Urothelial Cell Carcinoma

Tung

Wen

Wang

et al. 2019

JCM

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“…The thermocycling conditions maintained were as follows: 95°C for 30 sec, then 40 cycles of 95°C for 5 sec followed by 60°C for 30 sec. The relative expression level of lincRNA-p21 was normalized to internal control GAPDH, and quantified using the 2 −ΔΔCq cycle threshold method (13).…”

Section: Methodsmentioning

confidence: 99%

lincRNA‑p21 inhibits the progression of non‑small cell lung cancer via targeting miR‑17‑5p

Jiang

Zhou

et al. 2018

Oncol Rep

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Non-small-cell lung cancer (NSCLC) is well established as one of the major subtypes of human lung cancer. NSCLC is characterized by a high incidence rate and poor patient prognosis. Previous studies have identified that long intergenic non-coding RNA (lincRNA) serves a key role in the development of tumor and malignant metastasis. However, the majority of the underlying mechanisms for lincRNA deregulation in various diseases, including cancer and diabetes, have not been completely elucidated. In the present study, the deregulation of lincRNA-p21 in NSCLC tumor tissues in comparison to adjacent healthy tissues was examined using reverse transcription-quantitative polymerase chain reaction. Furthermore, the effect of lincRNA-p21 overexpression and knockdown on different NSCLC cell lines was further investigated in vitro. The association between lincRNA-p21 expression and microRNA (miR)-17-5p level in NSCLC tumor cells was also investigated to clarify the underlying mechanism. The influence of miR-17-5p on different NSCLC cell lines A549 and PC9 were also examined in vitro using miR-17-5p mimics and inhibitors. Bioinformatics and luciferase assays were conducted to verify the direct binding sites on lincRNA-p21 for miR-17-5p. The results demonstrated that there was a significant low-expression of lincRNA-p21 in NSCLC tumor tissues, and lincRNA-p21 effectively inhibited the progression of lung cancer cells by suppressing cell proliferation and migration and promoting cell apoptosis. An evident negative association between lincRNA-p21 and miR-17-5p expression was observed, and the inhibitory effect of overexpressed lincRNA-p21 on lung cancer cells was counteracted by miR-17-5p. Bioinformatics and luciferase reporter analysis results confirmed that miR-17-5p is a direct target for lincRNA-p21. The present study provides evidence for lincRNA-p21 to inhibit the progression of NSCLC via direct targeting of a miR-17-5p associated signaling pathway.

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“…LncRNAs regulate gene expression at epigenetic, transcriptional, and post-transcriptional levels (Chen et al, 2019). In lung cancers, HOX antisense intergenic RNA (HOTAIR), a well-studied lncRNA, has been shown to correlate with metastasis and poor prognosis (Loewen et al, 2014;Wang et al, 2018). In addition, aside from regulating expression levels of genes, lncRNA structures govern a complex post-transcriptional regulatory program in diseases (Fujimoto et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Detection of Allosteric Effects of lncRNA Secondary Structures Altered by SNPs in Human Diseases

Ding

Bai

et al. 2020

Front. Cell Dev. Biol.

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Recent studies have shown that structuralized long non-coding RNAs (lncRNAs) play important roles in genetic and epigenetic processes. The spatial structures of most lncRNAs can be altered by distinct in vivo and in vitro cellular environments, as well as by DNA structural variations, such as single-nucleotide polymorphisms (SNPs) and variants (SNVs). In the present study, we extended candidate SNPs that had linkage disequilibria with those significantly associated with lung diseases in genome-wide association studies in order to investigate potential disease mechanisms originating from SNP structural changes of host lncRNAs. Following accurate alignments, we recognized 115 ternary-relationship pairs among 41 SNPs, 10 lncRNA transcripts, and 1 type of lung disease (adenocarcinoma of the lung). Then, we evaluated the structural heterogeneity induced by SNP alleles by developing a local-RNA-structure alignment algorithm and employing randomized strategies to determine the significance of structural variation. We identified four ternary-relationship pairs that were significantly associated with SNPinduced lncRNA allosteric effects. Moreover, these conformational changes disrupted the interactive regions and binding affinities of lncRNA-HCG23 and TF-E2F6, suggesting that these may represent regulatory mechanisms in lung diseases. Taken together, our findings support that SNP-induced changes in lncRNA conformations regulate many biological processes, providing novel insight into the role of the lncRNA "structurome" in human diseases.

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HOTAIR lncRNA SNPs rs920778 and rs1899663 are associated with smoking, male gender, and squamous cell carcinoma in a Chinese lung cancer population

Cited by 34 publications

References 34 publications

Impact of Long Non-Coding RNA HOTAIR Genetic Variants on the Susceptibility and Clinicopathologic Characteristics of Patients with Urothelial Cell Carcinoma

Impact of Long Non-Coding RNA HOTAIR Genetic Variants on the Susceptibility and Clinicopathologic Characteristics of Patients with Urothelial Cell Carcinoma

lincRNA‑p21 inhibits the progression of non‑small cell lung cancer via targeting miR‑17‑5p

Detection of Allosteric Effects of lncRNA Secondary Structures Altered by SNPs in Human Diseases

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