<p>Glucosamine-6-Phosphate Isomerase 1 Promotes Tumor Progression and Indicates Poor Prognosis in Hepatocellular Carcinoma</p>

Abstract

Purpose: Reprogramming of metabolic pathways is a hallmark of the pathological changes that occur in cancer cells. Under physiological conditions, glucosamine-6-phosphate isomerase 1 (GNPDA1) promotes the conversion of the hexosamine system to the glycolytic pathway and may, therefore, affect energy metabolism. Low expression of GNPDA1 has been reported in normal liver tissues, however, analysis of the hepatocellular carcinoma (HCC) database in The Cancer Genome Atlas (TCGA) revealed that GNPDA1 was highly expressed in HCC tissues. The purpose of this study was to explore the role of GNPDA1 in HCC. Patients and Methods: We analyzed the expression of GNPDA1 in HCC tissues as well as the clinical outcomes of HCC patients with high or low expression of GNPDA1. Furthermore, the relationship between the expression of GNPDA1 and advanced tumor stage, TNM stage, grade, gender, or metastasis was assessed using high-throughput RNA sequencing data from TCGA HCC cohort and Kaplan-Meier survival analysis. The expression of GNPDA1 in HCC and normal liver cell lines was subsequently detected by qRT-PCR and Western blot analysis. Additionally, the effects of GNPDA1 knockdown in SMMC-7721 and Huh7 cell lines were examined. Cell proliferation, migration, invasion, and apoptosis following knockdown were investigated by the MTT assay and EdU, cell cycle, apoptosis, transwell, and wound healing analyses. Results: There was a significant association between high GNPDA1 expression and advanced tumor stage, TNM stage or grade, but not with gender. High GNPDA1 expression was associated with poor prognosis in patients with HCC. Furthermore, the MTT assay and EdU, cell cycle, apoptosis, wound healing, and transwell analyses revealed that GNPDA1 promoted the proliferation, migration, and invasion of HCC cells and inhibited apoptosis. Conclusion: The results of this study suggest that GNPDA1 may serve as a novel prognostic biomarker and therapeutic target for HCC.

MiR-548d-3p Promotes Gastric Cancer by Targeting RSK4

“…After reverse transcription of RNA into cDNA, RT-PCR was performed using cDNA as described previously. 33 Primers for RT-PCR, designed using DNAMAN 10.0, are presented in Table 2 .…”

“…: E112-01, Nanjing, China), Western blot analysis was performed as previously described. 33 Anti-RSK4 antibody (Abcam, catalog number: ab76117, 1:1000, Shanghai, China) and anti-GAPDH antibody (Abcam, catalog number: ab8245, 1:2000, Shanghai, China) were used as primary antibodies. Goat anti-mouse IgG (Abcam, catalog number: ab6789, 1:2000, Shanghai, China) and goat anti-rabbit IgG (Abcam, catalog number: ab6721, 1:2000, Shanghai, China) were used as secondary antibodies conjugated with horseradish peroxidase.…”

“…MTT (Beyotime, catalog number: ST316, Shanghai, China), EdU (Beyotime, catalog number: ST067, Shanghai, China), and propidium iodide (PI) (Beyotime, catalog number: ST511, Shanghai, China) were used to detect cell proliferation as previously described. 33 …”

“…After cell treatment, wound healing assay, Matrigel-free transwell plates, transwell plates with Matrigel, and transwell assay were performed for cell migration and invasiveness analyses. 33 …”

Prognostic value of a novel glycolysis-related gene expression signature for gastrointestinal cancer in the Asian population

“…Glucosamine-6-phosphate isomerase 1 (GNPDA1) can catalyze the conversion of glucosamine 6-phosphate to fructose 6-phosphate and thereby increase the raw materials for glycolysis [ 61 – 63 ], which enhances cancer progression. GNPDA1 plays important roles in cell proliferation, migration and invasion [ 64 , 65 ]. Elevated GNPDA1 expression levels are associated with poor prognosis in patients with HCC, pancreatic cancer and colorectal cancer [ 64 , 66 – 68 ].…”