MicroRNA‐488 inhibits proliferation and glycolysis in human prostate cancer cells by regulating PFKFB3

Abstract

Prostate cancer (PCa) remains the second leading cause of cancer‐related death among men in the United States, and its molecular mechanism remains to be elucidated. Recent studies have suggested that microRNAs may play an important role in cancer development and progression. By analyzing the Gene Expression Omnibus dataset, we found lower expression for miR‐488 in PCa than in normal tissues. Moreover, CCK‐8, EdU, glucose uptake, and lactate secrete assays revealed that overexpression of miR‐488 in PCa cell lines PC3 and DU145 resulted in inhibition of proliferation and glycolysis. In contrast, downregulation of miR‐488 expression promoted proliferation and glycolysis in PCa cells. Using a bioinformatic approach and dual‐luciferase reporter assays, we identified 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase, isoform3 (PFKFB3), as a direct target of miR‐488. Inhibition of PFKFB3 also suppressed PCa cell glycolysis and proliferation. Our study suggests that miR‐488 inhibits PCa cell proliferation and glycolysis by targeting PFKFB3, and thus, miR‐488 may be a novel therapeutic candidate for PCa.

Long noncoding RNA GSEC promotes neutrophil inflammatory activation by supporting PFKFB3-involved glycolytic metabolism in sepsis

“…However, the biological role of GSEC in sepsis remains unclear. PFKFB3 is a well-known regulator of glycolytic metabolism and plays an important role in cell survival and activation [ 20 – 22 ]. Based on our analysis, GSEC and PFKFB3 were co-expressed in leukocytes of septic patients and associated with neutrophil glycolysis.…”

“…6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a well-known regulator of glycolysis [ 19 ]. By mediating both the synthesis and degradation of fructose-2,6-bisphosphate, PFKFB3 is required for cell proliferation and survival [ 20 – 22 ]. A recent study showed that blockade of the glycolytic activator PFKFB3 in tumor endothelial cells reduced cancer cell invasion, intravasation, and metastasis, and improved the effect of chemotherapy on primary and metastatic tumors [ 23 ].…”

Mir‐488 alleviates chemoresistance and glycolysis of colorectal cancer by targeting PFKFB3

“…MiR‐488, situated in 1q25.2 and comprised of 1 exon, was weakly expressed in prostate cancer and gastrointestinal stromal tumors, besides serving a protective role within cartilage tissue of osteoarthritis patients 23‐25 . In addition to the clinical part, strongly expressed miR‐488 also impaired proliferative and invasive capability of gastric cancer cells 26 .…”

“…tumors, besides serving a protective role within cartilage tissue of osteoarthritis patients. [23][24][25] In addition to the clinical part, strongly expressed miR-488 also impaired proliferative and invasive capability of gastric cancer cells. 26 With regard to CRC, miR-488 was implied to retard progression of CRC, 12 and here we disclosed that lowly expressed miR-488 was predictive of poor CRC prognosis after chemotherapy (Table 1, Figures 1 and 2), which was a bright spot of this investigation.…”

MiR-652-5p elevated glycolysis level by targeting TIGAR in T-cell acute lymphoblastic leukemia

“…Given that miRs are reported to affect glycolysis level by targeting the genes coding glycolysis rate-limiting enzymes, such as PFKFB3 [ 16 ], GLUT-1 [ 17 ], and PFK1 [ 18 ], we reported that impaired miR-652-5p could slow the cell growth of T-ALL in vitro and prolong the survival time in vivo. We then found that impaired miR-652-5p could inhibit glycolysis by targeting TIGAR, thus suppressing PFKFB3 expression, which explained the molecular mechanism of T-ALL.…”