REV3L 3'UTR 460 T>C polymorphism in microRNA target sites contributes to lung cancer susceptibility.
REV3Lp, the catalytic subunit of DNA polymerase zeta, is the major participant in translesion DNA synthesis. Recent evidence suggests that REV3L has an important role in the maintenance of genome stability despite its mutagenic characteristics. Such a function makes it a cancer susceptibility candidate gene. To investigate association between REV3L polymorphisms and lung cancer risk in a Chinese population, we first genotyped 15 common polymorphisms of the REV3L gene and found that three single nucleotide polymorphisms (rs465646, rs459809 and rs1002481) were significantly associated with lung cancer risk. One of the strongest associations observed was for the 3'-terminal untranslated region (3'UTR) 460 T>C polymorphism (rs465646) (adjusted odds ratio (OR)=0.69 for TC/CC; P=0.007, compared with TT). Similar results were obtained in a subsequent replication study (adjusted OR=0.72; P=0.016). Combined data from the two studies of 1072 lung cancer patients and 1064 cancer-free controls generated an even stronger association (adjusted OR=0.71; P=3.04 Γ 10(-4)). This 3'UTR 460 T>C variant was predicted to modulate the binding of several micro RNAs. Surface plasmon resonance analysis and luciferase assays showed that the T allele demonstrated a stronger binding affinity for miR-25 and miR-32, resulting in significantly weaker reporter expression levels. Additional experiments revealed that miR-25/32 could downregulate endogenous REV3L. Furthermore, the tumor-suppressing role of REV3L was confirmed by the foci formation assay. These results support our hypothesis that the REV3L rs465646 variant modifies lung cancer susceptibility in Chinese Han population by affecting miRNA-mediated gene regulation.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
No citations found.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci. | 2020 | 30617275 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Comprehensive investigation of long non-coding RNA HOTAIR polymorphisms and cancer risk: a current meta-analysis encompassing 96,458 participants. | Krishna BM et al. | β | 2024 | β |
| Tetrahydrobiopterin metabolism attenuates ROS generation and radiosensitivity through LDHA S-nitrosylation: novel insight into radiogenic lung injury. | Feng Y et al. | β | 2024 | β |
| Leveraging the replication stress response to optimize cancer therapy. | Cybulla E et al. | β | 2023 | β |
| Rs15285, a functional polymorphism located in lipoprotein lipase, predicts the risk and prognosis of gastric cancer. | Shen K et al. | β | 2023 | β |
| A microRNA binding site polymorphism in the 3' UTR region of VEGF-A gene modifies colorectal cancer risk based on ethnicity: a meta-analysis. | Kontham SS et al. | β | 2022 | β |
| Genetic variant in miR-17-92 cluster binding sites is associated with esophageal squamous cell carcinoma risk in Chinese population. | Shen Y et al. | β | 2022 | β |
| SGNNMD: signed graph neural network for predicting deregulation types of miRNA-disease associations. | Zhang G et al. | β | 2022 | β |
| Developmental delay with hypotrophy associated with homozygous functionally relevant REV3L variant. | Halas A et al. | β | 2021 | β |
| DNA polymerase eta: A potential pharmacological target for cancer therapy. | Saha P et al. | β | 2021 | β |
| REV3L single nucleotide variants lead to increased susceptibility towards non-small cell lung cancer in the population of Jammu and Kashmir. | Jamwal RS et al. | β | 2021 | β |
| Association of variations in platinum resistance-related genes and prognosis in lung cancer patients. | Zhou YK et al. | β | 2020 | β |
| Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci. | Erzurumluoglu AM et al. | β | 2020 | β |
| Mutant POLQ and POLZ/REV3L DNA polymerases may contribute to the favorable survival of patients with tumors with POLE mutations outside the exonuclease domain. | Huang F et al. | β | 2020 | β |
| The SNP rs4846048 of MTHFR enhances the cervical cancer risk through association with miR-522: A preliminary report. | Zhou X et al. | β | 2020 | β |
| Iron-sulfur clusters in nucleic acid metabolism: Varying roles of ancient cofactors. | Khodour Y et al. | β | 2019 | β |
| MicroRNAβ29a enhances cisplatin sensitivity in nonβsmall cell lung cancer through the regulation of REV3L. | Chen X et al. | β | 2019 | β |
| Upregulation of miR-25 and miR-181 Family Members Correlates with Reduced Expression of ATXN3 in Lymphocytes from SCA3 Patients. | Krauss S et al. | β | 2019 | β |
| A myriad of roles of miR-25 in health and disease. | SΓ‘rkΓΆzy M et al. | β | 2018 | β |
| MicroRNA-340 inhibits the proliferation and promotes the apoptosis of colon cancer cells by modulating REV3L. | Arivazhagan R et al. | β | 2018 | β |
| A comprehensive experiment for molecular biology: Determination of single nucleotide polymorphism in human REV3 gene using PCR-RFLP. | Zhang X et al. | β | 2017 | β |
| A new functional IDH2 genetic variant is associated with the risk of lung cancer. | Li J et al. | β | 2017 | β |
| Whole exome-wide association study identifies a missense variant in SLC2A4RG associated with glioblastoma risk. | Zhao Y et al. | β | 2017 | β |
| DNA polymerase ΞΆ limits chromosomal damage and promotes cell survival following aflatoxin exposure. | Lin YC et al. | β | 2016 | β |
| REV3L, the catalytic subunit of DNA polymerase ΞΆ, is involved in the progression and chemoresistance of esophageal squamous cell carcinoma. | Zhu X et al. | β | 2016 | β |
| A Five-miRNA Panel Identified From a Multicentric Case-control Study Serves as a Novel Diagnostic Tool for Ethnically Diverse Non-small-cell Lung Cancer Patients. | Wang C et al. | β | 2015 | β |
| Eukaryotic DNA polymerase ΞΆ. | Makarova AV et al. | β | 2015 | β |
| Genetic variants in N-myc (and STAT) interactor and susceptibility to glioma in a Chinese Han population. | Meng D et al. | β | 2015 | β |
| High expression of N-myc (and STAT) interactor predicts poor prognosis and promotes tumor growth in human glioblastoma. | Meng D et al. | β | 2015 | β |
| MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium. | Buas MF et al. | β | 2015 | β |
| REV3L, a promising target in regulating the chemosensitivity of cervical cancer cells. | Yang L et al. | β | 2015 | β |
| REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells. | Wang W et al. | β | 2015 | β |
| SNP Regulation of microRNA Expression and Subsequent Colon Cancer Risk. | Mullany LE et al. | β | 2015 | β |
| The superoxide dismutase 1 3'UTR maintains high expression of the SOD1 gene in cancer cells: The involvement of the RNA-binding protein AUF-1. | Zhang S et al. | β | 2015 | β |
| Translesion polymerase genes polymorphisms and haplotypes influence survival of osteosarcoma patients. | GoriΔar K et al. | β | 2015 | β |
| MicroRNA binding site polymorphisms as biomarkers in cancer management and research. | Cipollini M et al. | β | 2014 | β |
| Polymorphisms in translesion polymerase genes influence treatment outcome in malignant mesothelioma. | GoriΔar K et al. | β | 2014 | β |
| Potentially functional SNPs (pfSNPs) as novel genomic predictors of 5-FU response in metastatic colorectal cancer patients. | Wang J et al. | β | 2014 | β |
| Regulatory mutations in the A2M gene are involved in the mastitis susceptibility in dairy cows. | Wang XG et al. | β | 2014 | β |
| Somatic retrotransposition in human cancer revealed by whole-genome and exome sequencing. | Helman E et al. | β | 2014 | β |
| Targeting the microRNA-regulating DNA damage/repair pathways in cancer. | Bottai G et al. | β | 2014 | β |
| Association between SNPs in interferon regulatory factor 2 (IRF-2) gene and resistance to Aeromonas hydrophila in freshwater mussel Hyriopsis cumingii. | Wang G et al. | β | 2013 | β |
| DNA polymerase ΞΆ as a potential biomarker of chemoradiation resistance and poor prognosis for cervical cancer. | Shi TY et al. | β | 2013 | β |
| Evaluation of genetic variants in microRNA biosynthesis genes and risk of breast cancer in Chinese women. | Jiang Y et al. | β | 2013 | β |
| Genetic variation in a miR-335 binding site in BIRC5 alters susceptibility to lung cancer in Chinese Han populations. | Zu Y et al. | β | 2013 | β |
| MicroRNA polymorphisms and environmental smoke exposure as risk factors for oesophageal squamous cell carcinoma. | Wang Y et al. | β | 2013 | β |
| MicroRNAs and DNA damage response: implications for cancer therapy. | Wang Y et al. | β | 2013 | β |
| Polymorphisms of microRNA sequences or binding sites and lung cancer: a meta-analysis and systematic review. | Chen Z et al. | β | 2013 | β |
| The role of microRNAs in lung cancer progression. | Zhang WC et al. | β | 2013 | β |
| The roles of DNA polymerase ΞΆ and the Y family DNA polymerases in promoting or preventing genome instability. | Sharma S et al. | β | 2013 | β |