miR‑21‑5p targets PDHA1 to regulate glycolysis and cancer progression in gastric cancer

Liu, Zhuo; Yu, Miao; Fei, Bingyuan; Fang, Xuedong; Ma, Tiantian; Wang, Dong‐Xin

doi:10.3892/or.2018.6695

Cited by 51 publications

(55 citation statements)

References 22 publications

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“…For instance, miR-129-5p inhibited glucose metabolism and proliferation in GC cells via targeting SLC2A3 (solute carrier family 2 member 3), a glucose transporter (30). Via targeting PDHA1, miR-21-5p overexpression could significantly promote glycolysis and accelerate GC progression (31).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-4290 suppresses PDK1-mediated glycolysis to enhance the sensitivity of gastric cancer cell to cisplatin

Qian

Wang

et al. 2020

Braz J Med Biol Res

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The development of chemotherapy resistance significantly impairs the efficiency of chemotherapy, but the underlying mechanisms of chemotherapy resistance in gastric cancer (GC) are complicated and still need to be further explored. Here, we aimed to reveal the effects of miR-4290/PDK1 (pyruvate dehydrogenase kinase 1) axis on chemotherapy resistance of GC in vitro. The expression patterns of miR-4290 in GC tissues and cell lines were determined by real-time quantitative PCR. Kaplan-Meier was used to assess the relationship between miR-4290 expression levels and patients' overall survival. CCK-8 and flow cytometry technologies were applied to detect cell proliferation and apoptosis. The luciferase gene reporter assay was used to evaluate the interaction between miR-4290 and PDK1. miR-4290 was lowly expressed in GC tissues and cell lines, which was closely associated with the shorter overall survival of GC patients. miR-4290 mimics significantly inhibited cell proliferation and induced cell apoptosis, as well as induced a significant reduction in the expression of PDK1. Moreover, miR-4290 significantly inhibited glycolysis and decreased the IC50 value to cisplatin in SGC7901 cells, whereas these effects were abolished and cell apoptosis was promoted when PDK1 was overexpressed. In conclusion, this study revealed that miR-4290 suppressed PDK1-mediated glycolysis to enhance the sensitivity of GC cells to cisplatin.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-4290 suppresses PDK1-mediated glycolysis to enhance the sensitivity of gastric cancer cell to cisplatin

Qian

Wang

et al. 2020

Braz J Med Biol Res

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“… 30 , 31 The underlying molecular mechanism of glycolysis in GC may involve the abnormal activity of glycolysis genes, such as increased expression of HK II and the suppression of PDH. 32 , 33 Elevated HK II expression in non-small-cell lung cancer, colon cancer, myeloma, breast cancer and pancreatic cancer cells compared with normal tissues has been reported. 34 , 35 For example, a high glycolytic rate has been shown to be closely associated with the increased expression of HK II and its binding with voltage-dependent anionic channel (VDAC) in the mitochondria of breast cancer cells, resulting in apoptosis inhibition and chemotherapeutic agent resistance.…”

Section: Discussionmentioning

confidence: 99%

<p>Monoamine Oxidase A is a Major Mediator of Mitochondrial Homeostasis and Glycolysis in Gastric Cancer Progression</p>

Chen¹,

Li²,

Sun³

et al. 2020

CMAR

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Objective: Monoamine oxidase A (MAO-A) is a mitochondrial protein involved in tumourigenesis in different types of cancer. However, the biological function of MAO-A in gastric cancer development remains unknown. Methods: We examined MAO-A expression in gastric cancer tissues and in gastric cancer cell lines by immunohistochemistry and Western blot analyses. CCK8, FACS and bromodeoxyuridine incorporation assays were performed to assess the effects of MAO-A on gastric cancer cell proliferation. The role of MAO-A in mitochondrial function was determined through MitoSOX Red staining, ATP generation and glycolysis assays. Results: In the present study, we observed that MAO-A was significantly upregulated in gastric cancer tissues and in AGS and MGC803 cells. The observed MAO-A inhibition indicated decreased cell cycle progression and proliferation. Silencing MAO-A expression was associated with suppressed migration and invasion of gastric cancer cells in vitro. Moreover, alleviated mitochondrial damage in these cells was demonstrated by decreased levels of mitochondrial reactive oxygen species and increased ATP generation. MAO-A knockdown also regulated the expression of the glycolysis rate-limiting enzymes hexokinase 2 and pyruvate dehydrogenase. Finally, we observed that the glycolysis-mediated effect was weakened in AGS and MGC803 cells when MAO-A was blocked. Conclusion: The findings of the present study indicate that MAO-A is responsible for mitochondrial dysfunction and aerobic glycolysis, which in turn leads to the proliferation and metastasis of human gastric tumour cells.

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“…PdH is a heterogeneous tetramer, whose components are encoded by the PDHA1 and PDHB genes (26). The expression level of PDHA1 is the primary determinant of PdH activity (45,46). When the activity of PdHa1 is impaired, pyruvate can no longer be metabolized into acetyl-coa.…”

Section: Discussionmentioning

confidence: 99%

Conditional knockout of pyruvate dehydrogenase in mouse pancreatic β‑cells causes morphological and functional changes

Wang

Lai

et al. 2020

Mol Med Report

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diabetes mellitus is a metabolic disorder predominantly caused by the dysfunction of pancreatic β-cells. This dysfunction is partly caused by the dysregulation of pyruvate dehydrogenase (PdH), which acts as an important mediator of pyruvate oxidation after glycolysis and fuels the tricarboxylic acid cycle. Previous studies have reported decreased PdH expression in rodent models and humans with type 2 diabetes mellitus (T2dM), suggesting that PdH may play an important role in the development of T2dM. However, the mechanism by which PdH affects insulin secretion and β-cell development is poorly understood. Using immunofluorescence staining, the present study found that the expression of pyruvate dehydrogenase e1-α subunit (PdHa1; encoded by the PDHA1 gene) in the islets of type 2 diabetic mice (db/db mice) was lower than in wild-type mice, which indicated the possible association between PdHa1and diabetes. To further understand this mechanism, an inducible, islet-specific PdHa1 knockout mouse (βKo) model was established. The phenotype was authenticated, and the blood glucose levels and islet function between the βKo and control mice were compared. Though no changes were found in food intake, development status, fasting blood glucose or weight between the groups, the level of insulin secretion at 30 min after glucose injection in the βKO group was significantly lower compared with the control group. Furthermore, the performed of the βKo mice on the intraperitoneal glucose tolerance test was visibly impaired when compared with the control mice. Pancreatic tissues were collected for hematoxylin and eosin staining, immunohistochemical and confocal laser-scanning microscopy analysis. examination of the islets from the βKo mouse model indicated that abolishing the expression of PdH caused a compensatory islet enlargement and impaired insulin secretion.

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miR‑21‑5p targets PDHA1 to regulate glycolysis and cancer progression in gastric cancer

Cited by 51 publications

References 22 publications

MicroRNA-4290 suppresses PDK1-mediated glycolysis to enhance the sensitivity of gastric cancer cell to cisplatin

MicroRNA-4290 suppresses PDK1-mediated glycolysis to enhance the sensitivity of gastric cancer cell to cisplatin

<p>Monoamine Oxidase A is a Major Mediator of Mitochondrial Homeostasis and Glycolysis in Gastric Cancer Progression</p>

Conditional knockout of pyruvate dehydrogenase in mouse pancreatic β‑cells causes morphological and functional changes

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