Association between the flap endonuclease 1 gene polymorphisms and cancer susceptibility: An updated meta‐analysis

Moazeni‐Roodi, Abdolkarim; Ghavami, Saeid; Ansari, Hossein; Hashemi, Mohammad

doi:10.1002/jcb.28633

Cited by 10 publications

(8 citation statements)

References 30 publications

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“…As a structure-specific endonuclease, Flap endonuclease 1 (FEN1) plays vital roles in DSB repair via HR and MMEJ, as well as through the long patch base excision repair (LP-BER) pathway 19 , 27 , 28 . A higher level of FEN1 expression was detected in rapidly dividing cells, including various types of cancer cells, than in cells with normal division kinetics and is associated with enhanced malignancy and decreased survival rates 29 – 31 . In addition, robust evidence revealed that silencing FEN1 leads to enhanced cisplatin sensitivity in glioma 32 , indicating a potential strategy for glioma cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of miR-1193 leads to synthetic lethality in glioblastoma multiforme cells deficient of DNA-PKcs

Zhang

Tan

et al. 2020

Cell Death Dis

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Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and has the highest mortality rate among cancers and high resistance to radiation and cytotoxic chemotherapy. Although some targeted therapies can partially inhibit oncogenic mutation-driven proliferation of GBM cells, therapies harnessing synthetic lethality are ‘coincidental’ treatments with high effectiveness in cancers with gene mutations, such as GBM, which frequently exhibits DNA-PKcs mutation. By implementing a highly efficient high-throughput screening (HTS) platform using an in-house-constructed genome-wide human microRNA inhibitor library, we demonstrated that miR-1193 inhibition sensitized GBM tumor cells with DNA-PKcs deficiency. Furthermore, we found that miR-1193 directly targets YY1AP1, leading to subsequent inhibition of FEN1, an important factor in DNA damage repair. Inhibition of miR-1193 resulted in accumulation of DNA double-strand breaks and thus increased genomic instability. RPA-coated ssDNA structures enhanced ATR checkpoint kinase activity, subsequently activating the CHK1/p53/apoptosis axis. These data provide a preclinical theory for the application of miR-1193 inhibition as a potential synthetic lethal approach targeting GBM cancer cells with DNA-PKcs deficiency.

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Section: Introductionmentioning

confidence: 99%

Inhibition of miR-1193 leads to synthetic lethality in glioblastoma multiforme cells deficient of DNA-PKcs

Zhang

Tan

et al. 2020

Cell Death Dis

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“…The association between this SNP and the potential risk of different types of cancers, including esophageal, lung, gastrointestinal, gallbladder, breast cancer in Chinese and Iran populations, glioma and childhood leukemia, has been previously studied. The rs4246215 variant was also associated with colorectal cancer in East Asians and the Chinese population (Chou et al 2017;Moazeni-Roodi et al 2019).…”

Section: Discussionmentioning

confidence: 96%

Repurposing Non-invasive prenatal testing data; population study of single nucleotide variants associated with colorectal cancer and Lynch syndrome

Forgacova

Gazdarica

Budiš

et al. 2021

Preprint

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PURPOSE: In our previous work, we described genomic data generated through non-invasive prenatal testing (NIPT) based on low-coverage massively parallel whole-genome sequencing of total plasma DNA of pregnant women in Slovakia as a valuable source of population specific data. In the present study, we used these data to determine the population allele frequency of common risk variants located in genes associated with colorectal cancer (CRC) and Lynch syndrome (LS). METHODS: Allele frequencies of identified variants were compared with six world populations to detect significant differences between populations. Finally, we interpreted variants and searched for functional consequences and clinical significance of variants using publicly available databases.RESULTS: Although we could not identify any pathogenic variants associated with CRC or LS in the Slovak population using NIPT data, we observed significant differences in the allelic frequency of risk CRC variants previously reported in GWAS and common variants located in genes associated with LS. CONCLUSION: As Slovakia is the third country with the highest incidence of CRC per 100 000 population in the world, we highlight a need for studies dedicated to the cause of such a high incidence of CRC in Slovakia. We also assume that extensive cross-country data aggregation of NIPT results would represent an unprecedented source of information about human genome variation, also in cancer research.

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Section: Discussionmentioning

confidence: 99%

Repurposing non‑invasive prenatal testing data: Population study of single nucleotide variants associated with colorectal cancer and Lynch syndrome

et al. 2021

View full text Add to dashboard Cite

In our previous work, genomic data generated through non-invasive prenatal testing (NIPT) based on low-coverage massively parallel whole-genome sequencing of total plasma DNA of pregnant women in Slovakia was described as a valuable source of population specific data. In the present study, these data were used to determine the population allele frequency of common risk variants located in genes associated with colorectal cancer (CRC) and Lynch syndrome (LS). Allele frequencies of identified variants were compared with six world populations to detect significant differences between populations. Finally, variants were interpreted, functional consequences were searched for and clinical significance of variants was investigated using publicly available databases. Although the present study did not identify any pathogenic variants associated with CRC or LS in the Slovak population using NIPT data, significant differences were observed in the allelic frequency of risk CRC variants previously reported in genome-wide association studies and common variants located in genes associated with LS. As Slovakia is one of the leading countries with the highest incidence of CRC among male patients in the world, there is a need for studies dedicated to investigating the cause of such a high incidence of CRC in Slovakia. The present study also assumed that extensive cross-country data aggregation of NIPT results would represent an unprecedented source of information concerning human genome variation in cancer research.

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Association between the flap endonuclease 1 gene polymorphisms and cancer susceptibility: An updated meta‐analysis

Cited by 10 publications

References 30 publications

Inhibition of miR-1193 leads to synthetic lethality in glioblastoma multiforme cells deficient of DNA-PKcs

Inhibition of miR-1193 leads to synthetic lethality in glioblastoma multiforme cells deficient of DNA-PKcs

Repurposing Non-invasive prenatal testing data; population study of single nucleotide variants associated with colorectal cancer and Lynch syndrome

Repurposing non‑invasive prenatal testing data: Population study of single nucleotide variants associated with colorectal cancer and Lynch syndrome

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