Downregulation of glucose‑6‑phosphate dehydrogenase by microRNA‑1 inhibits the growth of pituitary tumor cells
Author(s) -
Chao He,
Jun Yang,
Jiawang Ding,
Song Li,
Hui Wu,
Yan Xiong,
Fei Zhou,
Yu-Rong Jiang,
Lin Teng,
Jian Yang
Publication year - 2018
Publication title -
oncology reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.094
H-Index - 96
eISSN - 1791-2431
pISSN - 1021-335X
DOI - 10.3892/or.2018.6755
Subject(s) - oncogene , pituitary tumors , carcinogenesis , biology , cancer research , apoptosis , glucose 6 phosphate dehydrogenase , nicotinamide adenine dinucleotide phosphate , microrna , downregulation and upregulation , cell cycle , cell growth , molecular medicine , western blot , tumor progression , pentose phosphate pathway , pituitary neoplasm , cancer , glycolysis , endocrinology , pituitary gland , enzyme , dehydrogenase , biochemistry , hormone , gene , genetics , oxidase test
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.
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