N6-methyladenosine-related single-nucleotide polymorphism analyses identify oncogene RNFT2 in bladder cancer
Abstract Background Single-nucleotide polymorphisms (SNPs) in N6-methyladenosine (m6A) related genetic locus play significant roles in tumorigenesis and development. The expression level of many oncogenes and tumour suppressor genes changed because of m6A-associated SNPs. In addition, the relationsh...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-10-01
|
| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-022-02701-z |
| _version_ | 1828161093542871040 |
|---|---|
| author | Jiancheng Lv Qiang Song Kexin Bai Jie Han Hao Yu Kai Li Juntao Zhuang Xiao Yang Haiwei Yang Qiang Lu |
| author_facet | Jiancheng Lv Qiang Song Kexin Bai Jie Han Hao Yu Kai Li Juntao Zhuang Xiao Yang Haiwei Yang Qiang Lu |
| author_sort | Jiancheng Lv |
| collection | DOAJ |
| description | Abstract Background Single-nucleotide polymorphisms (SNPs) in N6-methyladenosine (m6A) related genetic locus play significant roles in tumorigenesis and development. The expression level of many oncogenes and tumour suppressor genes changed because of m6A-associated SNPs. In addition, the relationship between m6A-SNP and bladder cancer (BCa) has not been well studied. Methods We screened m6A-SNPs in BCa by combining m6A-SNPs data and GWAS-SNPs data. Expression quantitative trait loci (eQTL) and differential expression gene (DEGs) analyses were performed. In ring finger protein, transmembrane 2 (RNFT2), rs3088107 (C > G) was found to have significant eQTL signals and make RNFT2 gene differentially-regulated mostly in BCa. We validated the expression level of RNFT2 in 32 pairs of BCa tissues and eight BCa cell lines by quantitative real-time PCR (qRT-PCR). Functional assays were performed to investigate the role of rs3088107 and RNFT2 in BCa in vitro. Results We identified 673 m6A-SNPs, which were associated with BCa. Of these m6A-SNPs, 221 showed eQTL signals, amongst which, rs3088107 in RNFT2 showed significant eQTL signals. Results of bioinformatic analyses showed that 11 genes with m6A-SNPs had a differential expression level in BCa. RNFT2 was predicted to be significantly up-regulated in BCa. The qRT-PCR results validated that RNFT2 was highly expressed in our own BCa tissues and cell lines. High expression of RNFT2 also indicated a worse overall survival. We also revealed that rs3088107 (C > G) could inhibit the expression and m6A modification of RNFT2 by qRT-PCR, western-blot and m6A-RIP assays. Moreover, the results of functional assays indicated that RNFT2 promoted BCa cell proliferation and migration. Conclusion This research found that m6A-SNPs were associated with oncogene RNFT2 in BCa. Furthermore, m6A-SNPs showed great application potential as a new BCa diagnostic biomarker and prognostic indicator. |
| first_indexed | 2024-04-12T00:33:13Z |
| format | Article |
| id | doaj.art-75ae5045dec94f03942bf3763be0c52d |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-12T00:33:13Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-75ae5045dec94f03942bf3763be0c52d2022-12-22T03:55:17ZengBMCCancer Cell International1475-28672022-10-0122111410.1186/s12935-022-02701-zN6-methyladenosine-related single-nucleotide polymorphism analyses identify oncogene RNFT2 in bladder cancerJiancheng Lv0Qiang Song1Kexin Bai2Jie Han3Hao Yu4Kai Li5Juntao Zhuang6Xiao Yang7Haiwei Yang8Qiang Lu9Department of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityAbstract Background Single-nucleotide polymorphisms (SNPs) in N6-methyladenosine (m6A) related genetic locus play significant roles in tumorigenesis and development. The expression level of many oncogenes and tumour suppressor genes changed because of m6A-associated SNPs. In addition, the relationship between m6A-SNP and bladder cancer (BCa) has not been well studied. Methods We screened m6A-SNPs in BCa by combining m6A-SNPs data and GWAS-SNPs data. Expression quantitative trait loci (eQTL) and differential expression gene (DEGs) analyses were performed. In ring finger protein, transmembrane 2 (RNFT2), rs3088107 (C > G) was found to have significant eQTL signals and make RNFT2 gene differentially-regulated mostly in BCa. We validated the expression level of RNFT2 in 32 pairs of BCa tissues and eight BCa cell lines by quantitative real-time PCR (qRT-PCR). Functional assays were performed to investigate the role of rs3088107 and RNFT2 in BCa in vitro. Results We identified 673 m6A-SNPs, which were associated with BCa. Of these m6A-SNPs, 221 showed eQTL signals, amongst which, rs3088107 in RNFT2 showed significant eQTL signals. Results of bioinformatic analyses showed that 11 genes with m6A-SNPs had a differential expression level in BCa. RNFT2 was predicted to be significantly up-regulated in BCa. The qRT-PCR results validated that RNFT2 was highly expressed in our own BCa tissues and cell lines. High expression of RNFT2 also indicated a worse overall survival. We also revealed that rs3088107 (C > G) could inhibit the expression and m6A modification of RNFT2 by qRT-PCR, western-blot and m6A-RIP assays. Moreover, the results of functional assays indicated that RNFT2 promoted BCa cell proliferation and migration. Conclusion This research found that m6A-SNPs were associated with oncogene RNFT2 in BCa. Furthermore, m6A-SNPs showed great application potential as a new BCa diagnostic biomarker and prognostic indicator.https://doi.org/10.1186/s12935-022-02701-zBladder cancerSingle-nucleotide polymorphismsN6-methyladenosineRing finger proteinTransmembrane 2Proliferation |
| spellingShingle | Jiancheng Lv Qiang Song Kexin Bai Jie Han Hao Yu Kai Li Juntao Zhuang Xiao Yang Haiwei Yang Qiang Lu N6-methyladenosine-related single-nucleotide polymorphism analyses identify oncogene RNFT2 in bladder cancer Cancer Cell International Bladder cancer Single-nucleotide polymorphisms N6-methyladenosine Ring finger protein Transmembrane 2 Proliferation |
| title | N6-methyladenosine-related single-nucleotide polymorphism analyses identify oncogene RNFT2 in bladder cancer |
| title_full | N6-methyladenosine-related single-nucleotide polymorphism analyses identify oncogene RNFT2 in bladder cancer |
| title_fullStr | N6-methyladenosine-related single-nucleotide polymorphism analyses identify oncogene RNFT2 in bladder cancer |
| title_full_unstemmed | N6-methyladenosine-related single-nucleotide polymorphism analyses identify oncogene RNFT2 in bladder cancer |
| title_short | N6-methyladenosine-related single-nucleotide polymorphism analyses identify oncogene RNFT2 in bladder cancer |
| title_sort | n6 methyladenosine related single nucleotide polymorphism analyses identify oncogene rnft2 in bladder cancer |
| topic | Bladder cancer Single-nucleotide polymorphisms N6-methyladenosine Ring finger protein Transmembrane 2 Proliferation |
| url | https://doi.org/10.1186/s12935-022-02701-z |
| work_keys_str_mv | AT jianchenglv n6methyladenosinerelatedsinglenucleotidepolymorphismanalysesidentifyoncogenernft2inbladdercancer AT qiangsong n6methyladenosinerelatedsinglenucleotidepolymorphismanalysesidentifyoncogenernft2inbladdercancer AT kexinbai n6methyladenosinerelatedsinglenucleotidepolymorphismanalysesidentifyoncogenernft2inbladdercancer AT jiehan n6methyladenosinerelatedsinglenucleotidepolymorphismanalysesidentifyoncogenernft2inbladdercancer AT haoyu n6methyladenosinerelatedsinglenucleotidepolymorphismanalysesidentifyoncogenernft2inbladdercancer AT kaili n6methyladenosinerelatedsinglenucleotidepolymorphismanalysesidentifyoncogenernft2inbladdercancer AT juntaozhuang n6methyladenosinerelatedsinglenucleotidepolymorphismanalysesidentifyoncogenernft2inbladdercancer AT xiaoyang n6methyladenosinerelatedsinglenucleotidepolymorphismanalysesidentifyoncogenernft2inbladdercancer AT haiweiyang n6methyladenosinerelatedsinglenucleotidepolymorphismanalysesidentifyoncogenernft2inbladdercancer AT qianglu n6methyladenosinerelatedsinglenucleotidepolymorphismanalysesidentifyoncogenernft2inbladdercancer |