Significance of Methylation of FBP1 Gene in Non-Small Cell Lung Cancer

Abstract

Because NSCLC has poor overall prognosis and is frequently diagnosed at later stage, we aimed to seek novel diagnosis biomarkers or therapy target of the disease in this study. Fructose-1,6-bisphosphatase 1 (FBP1) is a rate-limiting enzyme in gluconeogenesis, which was usually lost in NSCLC due to abnormal methylation in promoter DNA sequence. The clinical data indicated that the methylation rate in FBP1 gene promoter was negatively related to the overall survival of the NSCLC patients. DNA methylation transferase inhibitor 5-aza treatment could significantly increase both expression levels of mRNA and protein in A549 cell line. On the other hand, silence of FBP1 in H460 cell line by using specific siRNA against FBP1 dramatically improved the cell proliferation and cell migration according to the date of FACS and transwell assays. All these findings implied the important roles of FBP1 expression in lung cancer development and progression and the potential use of the methylation status detected in FBP1 promoter region as a novel predictor for prognosis and therapeutic target for NSCLC patients.

Long noncoding RNA DANCR regulates proliferation and migration by epigenetically silencing FBP1 in tumorigenesis of cholangiocarcinoma

“…EZH2, the critical element of a methyltransferase named polycomb repressive complex 2 (PRC2) 31 , could serve as a master regulator of transcription that contributes to cancer development and progression via promoter hypermethylation of target gene 32 . Interestingly, transcriptional inactivation of FBP1 expression due to promoter region DNA hypermethylation was observed in hepatocellular carcinoma 25 , colon cancer 33 , gastric carcinogenesis 34 , basal-like breast cancer 24 and lung cancer 35,36 . Furthermore, recent studies have reported that epigenetic modifications like DNA and histone methylation could exhibit functional cooperation in heritable repression of gene activity 37–40 .…”

Fructose‐1,6‐bisphosphatase aggravates oxidative stress‐induced apoptosis in asthma by suppressing the Nrf2 pathway

“…Fructose‐1,6‐bisphosphatase (Fbp1) is a rate‐limiting enzyme of gluconeogenesis that catalyses the splitting of fructose‐1,6‐bisphosphate into fructose 6‐phosphate and inorganic phosphate 8 . Fbp1 reportedly plays a critical role in several diseases, including type 2 diabetes mellitus, 9 cancers 10‐12 and acute liver failure 13 . Kaur et al 9 reported that Fbp1 can be considered a potential target for the treatment of type 2 diabetes.…”

A Novel Prognostic and Predictive Signature for Lung Adenocarcinoma Derived from Combined Hypoxia and Infiltrating Immune Cell-Related Genes in TCGA Patients

“…In another study in the H460 large cell lung cancer cell line, silencing FBP1 significantly increased cellular proliferation and migration. 29 Therefore, FBP1 seems to consistently act as a tumor suppressor in different types of lung cancer.…”