Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma

Abstract

Lactate dehydrogenase A (LDHA) has been reported to be involved in the initiation and progression of tumors. However, the potential role of LDHA in pituitary adenoma (PA) remains unknown. In this study, we showed that the expression levels of LDHA mRNA and protein were significantly elevated in invasive PA samples, and positively correlated with higher Ki-67 index. Overexpression of LDHA in a PA cell line (GH3) promoted glucose uptake through the upregulation of glucose transporter-1 (Glut1), lactate secretion and induced cellular invasion by upregulation of matrix metalloproteinase2 (MMP2). LDHA also promoted GH3 cell proliferation through induction of cell cycle progression via activation of the Akt-GSK-3β-cyclinD1 pathway. Accordingly, oxamate-induced inhibition of LDHA suppressed glucose uptake, lactate secretion, invasion and proliferation in GH3 cells via down regulation of Glut1 and MMP2 expression and inhibition of the Akt-GSK-3β-cyclinD1 pathway. Moreover, oxamate induced GH3 cell apoptosis by increasing mitochondrial reactive oxygen species (ROS) generation. In vivo, LDHA overexpression promoted tumor growth, and oxamate delayed tumor growth. In primary PA cell cultures, oxamate also effectively suppressed invasion and proliferation. Our data indicate that LDHA is involved in promoting the progression of PA, and oxamate might be a promising therapeutic agent for the treatment of PA.

Long noncoding RNA LINC01391 restrained gastric cancer aerobic glycolysis and tumorigenesis via targeting miR-12116/CMTM2 axis

“…A number of enzymes have been confirmed to be involved in the aerobic glycolysis process, such as GLUT1, LDH-A [15,16]. Furthermore, LDH-A can accelerate cell invasion, proliferation and glucose uptake of pituitary adenoma (PA) cells via upmodulating GLUT1 [17]. Thus, we here determined the GLUT1 and LDH-A expressions following modulation of LINC01391 expression, and found that LINC01391 knockdown accelerated GLUT1 and LDH-A expressions, and meanwhile LINC01391 overexpression restrained GLUT1 and LDH-A expressions ( Figure 5), suggesting that LINC01391 may repress aerobic glycolysis of GC via upmodulating GLUT1 and LDH-A.…”

LncRNA FAM83H-AS1 Promotes Aerobic Glycolysis and Tumor Progression by Regulating miR-4684-5p/ZBTB38 Axis in Esophageal Squamous Cell Carcinoma

“…A number of enzymes are involved in the aerobic glycolysis process, including GLUT1 and LDH-A [19,29]. LDH-A can accelerate the invasion and proliferation of pituitary adenoma through the upmodulation of GLUT1 [30]. Thus, we determined the GLUT1 and LDH-A expressions following overexpression or downmodulation of FAM83H-AS1, and found that knockdown or overexpression of FAM83H-AS1 decreased or increased the expressions of GLUT1 and LDH-A ( Fig.3), as well as the downmodulation or upmodulation of glucose uptake and lactate production levels, indicating that FAM83H-AS1 may affect aerobic glycolysis process of ESCC partly by modulating GLUT1 and LDH-A.…”

Effect of simulated microgravity on metabolism of HGC‑27 gastric cancer cells

“…The high levels of lactate may be due to the Warburg effect (11), whereas the low glucose levels may be due to the elevated fructose-6-phosphokinase activity (16), high levels of glucose transporters (17) and increased type II hexokinase activity (18) in gastric cancer tissues. High activity levels of pyruvate kinase and lactate dehydrogenase are associated with cancer proliferation and poor prognosis (19,20), whereas their downregulation in vitro can impair tumor invasion (21,22). Based on these reports, several studies have investigated the influence of normal gravity on physiology and metabolism of cancer (23)(24)(25); however, the effect of gravity metabolism on cells, especially gastric cancer cells, is poorly understood.…”