Downregulation of glucose‑6‑phosphate dehydrogenase by microRNA‑1 inhibits the growth of pituitary tumor cells

Abstract

Pituitary tumors are generally intracranial neoplasms with high incidence and mortality rates. The investigation of novel factors involved in the tumorigenesis of pituitary tumors and the characterization of the underlying molecular mechanisms is urgently required for the diagnosis and treatment of pituitary tumors. Accumulating evidence has indicated that microRNAs (miRs) serve important roles in the initiation and progression of cancer. The present study found that miR-1 was significantly downregulated in pituitary tumor tissues upon reverse transcription-quantitative polymerase chain reaction analysis. Decreased expression of miR-1 was associated with the progression and worse prognosis of patients with pituitary tumors. The MTT assay showed that overexpression of miR-1 significantly suppressed proliferation. Highly expressed miR-1 promoted the apoptosis of pituitary tumor cells upon fluorescence-activated cell sorting analysis. Further molecular study revealed that glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the pentose phosphate pathway (PPP), was one of the targets of miR-1. Western blot assays showed that overexpression of miR-1 significantly decreased the protein level of G6PD in pituitary tumor cells without changing the mRNA level of G6PD. Consequently, oxidative PPP flux analysis revealed that suppression of G6PD by miR-1 decreased the production of nicotinamide adenine dinucleotide phosphate and the glycolysis of pituitary cancer cells. Restoration of the expression of G6PD significantly reversed the inhibitory effect of miR-1 on the PPP and the growth of pituitary tumor cells. Collectively, the present results uncovered the critical involvement of miR-1 in pituitary tumors, indicating that miR-1 is a potential therapeutic target for the treatment of pituitary tumors.

miR‑218 inhibits glucose metabolism in non‑small cell lung cancer via the NF‑κB signaling pathway

“…Several rate-limiting enzymes such as GLUT1, HK2, PFK1 and G6PD play crucial roles during these glucose metabolism processes (27). Previous studies have shown that these enzymes are regulated directly or indirectly by miRNAs (28)(29)(30)(31)(32). The present results indicated that the expression levels of these enzymes were decrease by miR-218 in NSCLC cell lines.…”

Downregulation of glucose-6-phosphate dehydrogenase contributes to diabetic neuropathic pain through upregulation of toll-like receptor 4 in rats

“…However, why and how G6PD was downregulated in DM rats remains unclear. Some researchers reported in other pathology models and pointed out that the causes of G6PD deficiency or downregulation mainly included four factors: DNA methylation, 33 histone deacetylation, 5,34 alteration in miRNA expression, 35,36 and DNA damage. 37 So, the upstream mechanism of G6PD deficiency or downregulation in diabetic neuropathic pain needs to be further investigated.…”

The Multiple Roles of Glucose-6-Phosphate Dehydrogenase in Tumorigenesis and Cancer Chemoresistance

“…In addition, EDTA, NADPH and G6P favor disruption of the dimer, whereas NADP + or certain metal ions favor the tetramer [14]. Additionally, the substrate-binding site and the dinucleotide-binding fingerprint are conserved in human G6PD with the sequences RIDHYLGKE (residues 198-206) and GxxGGDLA (residues [38][39][40][41][42][43][44], respectively [17].…”