ArticleCancer science2021
Methylation of NRN1 is a novel synthetic lethal marker of PI3K-Akt-mTOR and ATR inhibitors in esophageal cancer.
Article in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Epigenetic silencingCancer biology & therapy · 2026Article
- drGT: interpretable drug response prediction with attention-guided gene attribution on a drug-cell-gene heterogeneous graph.BMC bioinformatics · 2026Article
- L-Selenomethylselenocysteine Exerts Inhibitory Effects on the Progression of Esophageal Cancer by Targeting the PI3K/AKT Signaling Pathway.Recent patents on anti-cancer drug discovery · 2026Article
- Article
- Regulatory role of ezrin in esophageal cancer progression via the PI3K-AKT signaling pathway.Hereditas · 2025Article
- drGT: Attention-Guided Gene Assessment of Drug Response Utilizing a Drug-Cell-Gene Heterogeneous Network.ArXiv · 2025Article
- NEFL Modulates NRN1-Mediated Mitochondrial Pathway to Promote Diacetylmorphine-Induced Neuronal Apoptosis.Molecular neurobiology · 2025Article
- Aberrant DNA Methylation in Esophageal Squamous Cell Carcinoma and its Clinical Implications in Systemic Chemotherapy.International journal of medical sciences · 2025Review
- Epigenetic silencingCancer biology & therapy · 2024Article
- Epigenetic silencing of BEND4, a novel DNA damage repair gene, is a synthetic lethal marker for ATM inhibitor in pancreatic cancer.Frontiers of medicine · 2024Article
- Neuritin accelerates Schwann cell dedifferentiation via PI3K/Akt/mTOR signalling pathway during Wallerian degeneration.Journal of cellular and molecular medicine · 2024Article
- WTAP promotes proliferation of esophageal squamous cell carcinoma via mCancer science · 2024Article
- Methylation ofJournal of translational internal medicine · 2024Article
- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
- Circulating cell-free DNA-based methylation pattern in plasma for early diagnosis of esophagus cancer.PeerJ · 2024Review
- Epigenetic silencing ofEpigenomics · 2024Article
- Targeting epigenetic deregulations for the management of esophageal carcinoma: recent advances and emerging approaches.Cell biology and toxicology · 2023Review
- Long-read sequencing of diagnosis and post-therapy medulloblastoma reveals complex rearrangement patterns and epigenetic signatures.Cell genomics · 2023Article
- Epigenetic silencing of JAM3 promotes esophageal cancer development by activating Wnt signaling.Clinical epigenetics · 2022Article
- Development and validation of a prognostic model related to pyroptosis-related genes for esophageal squamous cell carcinoma using bioinformatics analysis.Journal of thoracic disease · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Wnt, PI3K-Akt-mTOR, and NF-κB pathways were reported to be involved in DNA damage repair (DDR). DDR-deficient cancers become critically dependent on backup DNA repair pathways. Neuritin 1 (NRN1) is reported to be involved in PI3K-Akt-mTOR, and its role in DDR remains unclear. Methylation-specific PCR, siRNA, flow cytometry, esophageal cancer cell lines, and xenograft mouse models were used to examine the role of NRN1 in esophageal cancer. The expression of NRN1 is frequently repressed by promoter region methylation in human esophageal cancer cells. NRN1 was methylated in 50.4% (510/1012) of primary esophageal cancer samples. NRN1 methylation is associated significantly with age (P < .001), tumor size (P < .01), TNM stage (P < .001), differentiation (P < .001) and alcohol consumption (P < .05). We found that NRN1 methylation is an independent prognostic factor for poor 5-y overall survival (P < .001). NRN1 inhibits colony formation, cell proliferation, migration, and invasion, and induces apoptosis and G1/S arrest in esophageal cancer cells. NRN1 suppresses KYSE150 and KYSE30 cells xenografts growth in nude mice. PI3K signaling is reported to activate ATR signaling by targeting CHK1, the downstream component of ATR. By analyzing the synthetic efficiency of NVP-BEZ235 (PI3K inhibitor) and VE-822 (an ATR inhibitor), we found that the combination of NVP-BEZ235 and VE-822 increased cytotoxicity in NRN1 methylated esophageal cancer cells, as well as KYSE150 cell xenografts. In conclusion, NRN1 suppresses esophageal cancer growth both in vitro and in vivo by inhibiting PI3K-Akt-mTOR signaling. Methylation of NRN1 is a novel synthetic lethal marker for PI3K-Akt-mTOR and ATR inhibitors in human esophageal cancer.
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