RT Journal Article
T1 The Roles of Imprinted SLC22A18 and SLC22A18AS Gene Overexpression Caused by Promoter CpG Island Hypomethylation as Diagnostic and Prognostic Biomarkers for Non-Small Cell Lung Cancer Patients.
A1 Noguera-Uclés, José Francisco
A1 Boyero, Laura
A1 Salinas, Ana
A1 Cordero Varela, Juan Antonio
A1 Benedetti, Johana Cristina
A1 Bernabé-Caro, Reyes
A1 Sánchez-Gastaldo, Amparo
A1 Alonso, Miriam
A1 Paz-Ares, Luis
A1 Molina-Pinelo, Sonia
K1 IMPT1
K1 NSCLC
K1 SLC22A18
K1 SLC22A18AS
K1 TSSC5
K1 biomarkers
K1 diagnostic
K1 genomic imprinting
K1 prognosis
AB Genomic imprinting is a process that involves one gene copy turned-off in a parent-of-origin-dependent manner. The regulation of imprinted genes is broadly dependent on promoter methylation marks, which are frequently associated with both oncogenes and tumor suppressors. The purpose of this study was to assess the DNA methylation patterns of the imprinted solute-carrier family 22 member 18 (SLC22A18) and SLC22A18 antisense (SLC22A18AS) genes in non-small cell lung cancer (NSCLC) patients to study their relevance to the disease. We found that both genes were hypomethylated in adenocarcinoma and squamous cell carcinoma patients. Due to this imprinting loss, SLC22A18 and SLC22A18AS were found to be overexpressed in NSCLC tissues, which is significantly more evident in lung adenocarcinoma patients. These results were validated through analyses of public databases of NSCLC patients. The reversed gene profile of both genes was achieved in vitro by treatment with ademetionine. We then showed that high SLC22A18 and SLC22A18AS expression levels were significantly associated with worsening disease progression. In addition, low levels of SLC22A18AS were also correlated with better overall survival for lung adenocarcinoma patients. We found that SLC22A18 and SLC22A18AS knockdown inhibits cell proliferation in vitro. All these results suggest that both genes may be useful as diagnostic and prognostic biomarkers in NSCLC, revealing novel therapeutic opportunities.
SN 2072-6694
YR 2020
FD 2020-07-27
LK https://hdl.handle.net/10668/27492
UL https://hdl.handle.net/10668/27492
LA en
DS RISalud
RD Apr 18, 2025