scholarly journals Four novel polymorphisms in long non-coding RNA HOTTIP are associated with the risk and prognosis of colorectal cancer

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Zhi Lv ◽  
Qian Xu ◽  
Liping Sun ◽  
Jing Wen ◽  
Xinxin Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Susceptibility ◽  
Human Cancer ◽  
Predictive Biomarkers ◽  
Nucleotide Polymorphisms ◽  
Specific Pcr ◽  
Non Coding Rna ◽  
And Function ◽  
Stratified Analysis ◽  
Long Non Coding Rna

AbstractBackground: The role of long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) as an oncogene in varieties of human cancer including colorectal cancer (CRC) has been extensively researched. The expression and function of lncRNAs could be affected by single nucleotide polymorphisms (SNPs), which are associated with cancer susceptibility and prognosis. However, no investigation has focused on the association between HOTTIP SNPs and CRC. The aim of the present study was to explore the association of polymorphisms in the lncRNA HOTTIP gene with CRC risk and prognosis. Methods: A total of 1848 subjects were enrolled in our study, including 884 CRC cases and 964 controls. Genotyping for five HOTTIP tagSNPs (rs3807598, rs17501292, rs2067087, rs17427960, and rs78248039) was performed by applying Kompetitive allele specific PCR (KASP). Results: The results showed three SNPs (rs3807598, rs2067087, and rs17427960) were associated with enhanced CRC risk both in overall and stratified analysis. One polymorphism, rs17501292, could improve the overall survival (OS) of CRC patients in the tumor of ulcerative/invasive-type subgroup. Conclusion: These findings suggest HOTTIP SNPs could potentially be predictive biomarkers for CRC risk and prognosis. The present study provides clues for further exploration of novel lncRNA-based genetic biomarkers to predict CRC susceptibility as well as clinical outcome.

scholarly journals Polymorphisms of a novel long non-coding RNA RP11-108K3.2 with colorectal cancer susceptibility and their effects on its expression

2019 ◽  
Vol 35 (1) ◽  
pp. 3-9
Author(s):  
Danjie Jiang ◽  
Mingjuan Jin ◽  
Ding Ye ◽  
Yingjun Li ◽  
Fangyuan Jing ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Susceptibility ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Chinese Populations ◽  
Lncrna Transcript ◽  
Validated Questionnaire ◽  
Non Coding Rna ◽  
Validation Set ◽  
Long Non Coding Rna

Background: RP11-108K3.2 was recently identified as a novel long non-coding RNA (lncRNA) transcript, and several single nucleotide polymorphisms (SNPs) have been identified in its coding region. This study aimed to explore the associations of tagSNPs in RP11-108K3.2 with the risk of colorectal cancer and their effects on its expression. Methods: A total of 821 colorectal cancer cases and 857 healthy controls were enrolled into this two-stage case-control study. Demographic characteristics and lifestyle information were collected by a validated questionnaire. Six tagSNPs were genotyped by using Sequenom MassARRAY platform. A total of 71 additional colorectal cancer cases were recruited, of which the genotypes of potential polymorphisms and the RP11-108K3.2 expression levels were determined. Results: In the discovery set, only the rs2470151 C/T polymorphism was found to have a promising association with the risk of colorectal cancer, and this polymorphism was further replicated in the validation set with a significantly decreased risk of colorectal cancer (adjusted odds ratio 0.73; 95% confidence interval 0.55, 0.97). Combined discovery set and validation set together, this negative association was found both in the heterozygote codominant model and the dominant model. Furthermore, colorectal cancer patients carrying rs2470151 CT/TT genotypes had a marginally lower RNA expression of RP11-108K3.2 than those carrying the CC genotype. Stratified analyses showed the association between rs2470151 and the risk of colorectal cancer were influenced by family history of cancer, smoking, alcohol consumption, and tea drinking. Conclusions: These findings suggest that RP11-108K3.2 rs2470151 had a significant association with the risk of colorectal cancer; this may help to predict the susceptibility of colorectal cancer in Chinese populations.

scholarly journals GWAS Links New Variant in Long Non-Coding RNA LINC02006 with Colorectal Cancer Susceptibility

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 465
Author(s):  
Ewa E. Hennig ◽  
Anna Kluska ◽  
Magdalena Piątkowska ◽  
Maria Kulecka ◽  
Aneta Bałabas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Susceptibility ◽  
Association Studies ◽  
Bioinformatic Analysis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Tumor Invasiveness ◽  
Non Coding Rna ◽  
New Variant ◽  
Long Non Coding Rna

Despite great efforts, most of the genetic factors contributing to the risk of colorectal cancer (CRC) remain undetermined. Including small but homogenous populations in genome-wide association studies (GWAS) can help us discover new common risk variants specific to the studied population. In this study, including 465 CRC patients and 1548 controls, a pooled DNA samples-based GWAS was conducted in search of genetic variants associated with CRC in a Polish population. Combined with a new method of selecting single-nucleotide polymorphisms (SNPs) for verification in individual DNA samples, this approach allowed the detection of five new susceptibility loci not previously reported for CRC. The discovered loci were found to explain 10% of the overall risk of developing CRC. The strongest association was observed for rs10935945 in long non-coding RNA LINC02006 (3q25.2). Three other SNPs were also located within genes (rs17575184 in NEGR1, rs11060839 in PIWIL1, rs12935896 in BCAS3), while one was intergenic (rs9927668 at 16p13.2). An expression quantitative trait locus (eQTL) bioinformatic analysis suggested that these polymorphisms may affect transcription factor binding sites. In conclusion, four of the identified variants were located within genes likely involved in tumor invasiveness and metastasis. Therefore, they could possibly be markers of poor prognosis in CRC patients.

scholarly journals Association Between Long Non-Coding RNA POLR2E rs3787016 Polymorphism and Cancer Susceptibility: A Meta-analysis of 8725 Cancer Cases and 10710 Controls

2020 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Saeid Ghavami ◽  
Mohsen Taheri ◽  
Mohammad Hashemi
Keyword(s):  
Breast Cancer ◽  
Web Of Science ◽  
Cancer Susceptibility ◽  
Meta Analysis ◽  
Positive Association ◽  
Cancer Development ◽  
Non Coding Rna ◽  
Stratified Analysis ◽  
The Relationship ◽  
Long Non Coding Rna

Objectives: Several studies have reported a correlation between the POLR2E rs3787016 polymorphism and cancer development, but findings are inconsistent. Therefore, we designed the current study to understand how rs3787016 polymorphism impacts cancer susceptibility. Methods: We searched the Scopus, Web of Science, and PubMed databases for studies related to the topic of interest published up to March 2019. A total of 11 relevant studies, encompassing 8,761 cancer cases and 10,534 controls, were retrieved and subject to quantitative analysis. The strength of the relationship was evaluated using the pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: Overall, the findings proposed a positive association between rs189037 polymorphism and susceptibility to cancer in homozygous (OR = 1.32, 95% CI = 1.11 - 1.57, P = 0.002, TT vs. CC), recessive (OR = 1.21, 95% CI = 1.06-1.39, P = 0.005, TT vs. CT + CC), and allele (OR = 1.12, 95% CI = 1.02-1.22, P = 0.021, T vs. C) genetic models. Stratified analysis showed that rs3787016 increased the risk of prostate and breast cancer. In addition, we found a significant association between the variant and increased cancer risk in Asian and Caucasian populations. Conclusions: In summary, the findings of the current meta-analysis suggest that the POLR2E rs3787016 polymorphism is an indicator of cancer susceptibility.

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

2018 ◽  
Vol 47 (3) ◽  
pp. 893-913 ◽  
Author(s):  
Qing Tang ◽  
Swei Sunny Hann
Keyword(s):  
Drug Resistance ◽  
Human Cancer ◽  
Critical Role ◽  
Stem Cell Differentiation ◽  
Human Diseases ◽  
Biological Functions ◽  
Protein Coding ◽  
Non Coding Rna ◽  
And Function ◽  
Long Non Coding Rna

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.

scholarly journals HOTTIP polymorphism may affect gastric cancer susceptibility by altering HOTTIP expression

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Ben-gang Wang ◽  
Yi-zhi Li ◽  
Han-xi Ding ◽  
Zhi Lv ◽  
Qian Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Risk ◽  
Disease Risk ◽  
Cancer Susceptibility ◽  
Recessive Model ◽  
Eqtl Analysis ◽  
Nucleotide Polymorphisms ◽  
Gastric Cancer Risk ◽  
Specific Pcr ◽  
Non Coding Rna

Abstract Background: Non-coding RNA polymorphisms can affect disease risk and prognosis by influencing gene expression. Here, we first investigated the association between single nucleotide polymorphisms (SNPs) of long non-coding RNA (lncRNA) HOTTIP and gastric cancer risk/prognosis. Methods: A total of five HOTTIP SNPs among 627 gastric cancer cases and 935 controls were tested by Kompetitive Allele Specific PCR (KASP) assay. The functional SNPs underwent eQTL analysis and the expression of HOTTIP was assessed by quantitative RT-PCR. Results: The rs2067087 and rs3807598 SNPs of HOTTIP increased susceptibility to gastric cancer (rs2067087: dominant model, P=0.008, odds ratio (OR) = 1.35; rs3807598: recessive model, P=0.037, OR = 1.29). Both HOTTIP rs2067087 and rs3807598 could affect the expression of mature lncRNA (P=0.003 and P=0.032, respectively). Conclusion: The rs2067087 and rs3807598 SNPs of HOTTIP are associated with gastric cancer risk, possibly by affecting the expression of mature HOTTIP.

scholarly journals The PVT1 lncRNA is a novel epigenetic enhancer of MYC, and a promising risk-stratification biomarker in colorectal cancer

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Kunitoshi Shigeyasu ◽  
Shusuke Toden ◽  
Tsuyoshi Ozawa ◽  
Takatoshi Matsuyama ◽  
Takeshi Nagasaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Aberrant Methylation ◽  
Enhancer Activity ◽  
Transcriptional Enhancers ◽  
Cancer Pathogenesis ◽  
Non Coding Rna ◽  
Genome Wide ◽  
A Genome ◽  
And Function ◽  
Long Non Coding Rna

Abstract Accumulating evidence suggests that dysregulation of transcriptional enhancers plays a significant role in cancer pathogenesis. Herein, we performed a genome-wide discovery of enhancer elements in colorectal cancer (CRC). We identified PVT1 locus as a previously unrecognized transcriptional regulator in CRC with a significantly high enhancer activity, which ultimately was responsible for regulating the expression of MYC oncogene. High expression of the PVT1 long-non-coding RNA (lncRNA) transcribed from the PVT1 locus was associated with poor survival among patients with stage II and III CRCs (p < 0.05). Aberrant methylation of the PVT1 locus inversely correlated with the reduced expression of the corresponding the PVT1 lncRNA, as well as MYC gene expression. Bioinformatic analyses of CRC-transcriptomes revealed that the PVT1 locus may also broadly impact the expression and function of other key genes within two key CRC-associated signaling pathways – the TGFβ/SMAD and Wnt/β-Catenin pathways. We conclude that the PVT1 is a novel oncogenic enhancer of MYC and its activity is controlled through epigenetic regulation mediated through aberrant methylation in CRC. Our findings also suggest that the PVT1 lncRNA expression is a promising prognostic biomarker and a potential therapeutic target in CRC.

scholarly journals m6A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Hongjiang Liu ◽  
Shan Qin ◽  
Changqi Liu ◽  
Le Jiang ◽  
Chen Li ◽  
...  
Keyword(s):  
Mrna Stability ◽  
Cancer Susceptibility ◽  
Human Cancer ◽  
Aerobic Glycolysis ◽  
Poor Survival ◽  
Non Coding Rna ◽  
Mrna Binding Protein ◽  
A Site ◽  
Mrna Binding ◽  
Long Non Coding Rna

AbstractN6-methyladenosine (m6A) has been identified to exert critical roles in human cancer; however, the regulation of m6A modification on glioblastoma multiforme (GBM) and long non-coding RNA (lncRNA) CASC9 (cancer susceptibility 9) is still unclear. Firstly, MeRIP-Seq revealed the m6A profile in the GBM. Moreover, the m6A-related lncRNA CASC9 expression was significantly elevated in the GBM tissue and its ectopic high expression was associated with poor survival, acting as an independent prognostic factor for GBM patients. Functionally, the aerobic glycolysis was promoted in the CASC9 overexpression transfection, which was inhibited in CASC9 knockdown in GBM cells. Mechanistically, m6A reader IGF2BP2 (insulin-like growth factor 2 mRNA binding protein 2) could recognize the m6A site of CASC9 and enhance its stability, then CASC9 cooperated with IGF2BP2, forming an IGF2BP2/CASC9 complex, to increase the HK2 (Hexokinase 2) mRNA stability. Our findings reveal that CASC9/IGF2BP2/HK2 axis promotes the aerobic glycolysis of GBM.

Sign in / Sign up

Export Citation Format

Share Document