The effect of SNPs in lncRNA as ceRNA on the risk and prognosis of hepatocellular carcinoma
Abstract Background Most susceptible loci of hepatocellular carcinoma (HCC) identified by genome-wide association studies (GWAS) are located in non-coding regions, and the mechanism of action remains unclear. The objective of this study was to explore the association of single nucleotide polymorphis...
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12864-022-09010-9 |
| _version_ | 1811210818334752768 |
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| author | Han Mo Xi Wang Guohua Ji Xiao Liang Yi Yang Wenjing Sun Xueyuan Jia Lidan Xu Yuandong Qiao Henan Zhou Wenhui Zhao Songbin Fu Xuelong Zhang |
| author_facet | Han Mo Xi Wang Guohua Ji Xiao Liang Yi Yang Wenjing Sun Xueyuan Jia Lidan Xu Yuandong Qiao Henan Zhou Wenhui Zhao Songbin Fu Xuelong Zhang |
| author_sort | Han Mo |
| collection | DOAJ |
| description | Abstract Background Most susceptible loci of hepatocellular carcinoma (HCC) identified by genome-wide association studies (GWAS) are located in non-coding regions, and the mechanism of action remains unclear. The objective of this study was to explore the association of single nucleotide polymorphisms (SNPs) on long non-coding RNAs (lncRNAs) that affect competing endogenous RNAs (ceRNA) regulation mechanism with the risk and prognosis of HCC. Methods Based on a set of bioinformatics strategies, eight lncRNA genes that affect HCC through the mechanism of lncRNA-mediated ceRNA were systematically screened, and 15 SNPs that affect microRNA (miRNA) binding in these lncRNA genes were annotated. Genotyping was performed in 800 HCC cases and 801 healthy controls to examine associations of these SNPs with HCC in a northeastern Chinese Han population. Results The GG, GC and GG + GC genotypes of HOTAIR rs7958904 were associated with a 0.65, 0.59 and 0.63-fold decreased HCC risk, respectively. In addition, HCC patients with PVT1 rs3931282 AA + GA genotypes were less prone to develop late-stage cancers in a stratified analysis of clinical characteristics. When stratified by clinical biochemical indexes, rs1134492 and rs10589312 in PVT1 and rs84557 in EGFR-AS1 showed significant associations with aspartate aminotransferase (AST), alanine aminotransferase (ALT) or AST/ALT ratio in HCC patients. Furthermore, we constructed potential ceRNA regulatory axes that might be affected by five positive SNPs to explain the causes of these genetic associations. Conclusions HOTAIR rs7958904, PVT1 rs3931282, rs1134492 and rs10589312, and EGFR-AS1 rs84557 might be predictors for HCC risk or prognosis. Our results provide new insights into how SNPs on lncRNA-mediated ceRNAs confer interindividual differences to occurrence and progression of HCC. |
| first_indexed | 2024-04-12T05:02:23Z |
| format | Article |
| id | doaj.art-3fe300cc4ad64b63a299611a25cc115e |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-12T05:02:23Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-3fe300cc4ad64b63a299611a25cc115e2022-12-22T03:46:58ZengBMCBMC Genomics1471-21642022-11-0123111310.1186/s12864-022-09010-9The effect of SNPs in lncRNA as ceRNA on the risk and prognosis of hepatocellular carcinomaHan Mo0Xi Wang1Guohua Ji2Xiao Liang3Yi Yang4Wenjing Sun5Xueyuan Jia6Lidan Xu7Yuandong Qiao8Henan Zhou9Wenhui Zhao10Songbin Fu11Xuelong Zhang12Laboratory of Medical Genetics, Harbin Medical UniversityDepartment of Gastroenterology, the First Affiliated Hospital, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityDepartment of Clinical Laboratory, Harbin Medical University Cancer HospitalDepartment of Internal Medicine, Harbin Medical University Cancer HospitalLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityAbstract Background Most susceptible loci of hepatocellular carcinoma (HCC) identified by genome-wide association studies (GWAS) are located in non-coding regions, and the mechanism of action remains unclear. The objective of this study was to explore the association of single nucleotide polymorphisms (SNPs) on long non-coding RNAs (lncRNAs) that affect competing endogenous RNAs (ceRNA) regulation mechanism with the risk and prognosis of HCC. Methods Based on a set of bioinformatics strategies, eight lncRNA genes that affect HCC through the mechanism of lncRNA-mediated ceRNA were systematically screened, and 15 SNPs that affect microRNA (miRNA) binding in these lncRNA genes were annotated. Genotyping was performed in 800 HCC cases and 801 healthy controls to examine associations of these SNPs with HCC in a northeastern Chinese Han population. Results The GG, GC and GG + GC genotypes of HOTAIR rs7958904 were associated with a 0.65, 0.59 and 0.63-fold decreased HCC risk, respectively. In addition, HCC patients with PVT1 rs3931282 AA + GA genotypes were less prone to develop late-stage cancers in a stratified analysis of clinical characteristics. When stratified by clinical biochemical indexes, rs1134492 and rs10589312 in PVT1 and rs84557 in EGFR-AS1 showed significant associations with aspartate aminotransferase (AST), alanine aminotransferase (ALT) or AST/ALT ratio in HCC patients. Furthermore, we constructed potential ceRNA regulatory axes that might be affected by five positive SNPs to explain the causes of these genetic associations. Conclusions HOTAIR rs7958904, PVT1 rs3931282, rs1134492 and rs10589312, and EGFR-AS1 rs84557 might be predictors for HCC risk or prognosis. Our results provide new insights into how SNPs on lncRNA-mediated ceRNAs confer interindividual differences to occurrence and progression of HCC.https://doi.org/10.1186/s12864-022-09010-9HOTAIRPVT1EGFR-AS1HCCRiskPrognosis |
| spellingShingle | Han Mo Xi Wang Guohua Ji Xiao Liang Yi Yang Wenjing Sun Xueyuan Jia Lidan Xu Yuandong Qiao Henan Zhou Wenhui Zhao Songbin Fu Xuelong Zhang The effect of SNPs in lncRNA as ceRNA on the risk and prognosis of hepatocellular carcinoma BMC Genomics HOTAIR PVT1 EGFR-AS1 HCC Risk Prognosis |
| title | The effect of SNPs in lncRNA as ceRNA on the risk and prognosis of hepatocellular carcinoma |
| title_full | The effect of SNPs in lncRNA as ceRNA on the risk and prognosis of hepatocellular carcinoma |
| title_fullStr | The effect of SNPs in lncRNA as ceRNA on the risk and prognosis of hepatocellular carcinoma |
| title_full_unstemmed | The effect of SNPs in lncRNA as ceRNA on the risk and prognosis of hepatocellular carcinoma |
| title_short | The effect of SNPs in lncRNA as ceRNA on the risk and prognosis of hepatocellular carcinoma |
| title_sort | effect of snps in lncrna as cerna on the risk and prognosis of hepatocellular carcinoma |
| topic | HOTAIR PVT1 EGFR-AS1 HCC Risk Prognosis |
| url | https://doi.org/10.1186/s12864-022-09010-9 |
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