<p>miR-1297 Suppresses Osteosarcoma Proliferation and Aerobic Glycolysis by Regulating PFKFB2</p>

Abstract

Background MiR-1297 is reported to function as a tumor suppressor of various cancers. However, the role of miR-1297 in the development of osteosarcoma (OS) has not been elaborated. The purpose of this study was to investigate the functional effects of miR-1297 on OS progression and the underlying mechanism. Methods The expression of protein and mRNA in OS cells was evaluated by Western blotting and quantitative real-time polymerase chain reaction. Cellular proliferation was investigated by cell counting kit-8, colony formation and apoptosis assays. Bioinformatics methods were used to predict target genes. The relationship between PFKFB2 and miR-1297 was demonstrated by dual-luciferase reporter assay. Metabolic changes in OS cells were monitored using an XF96 metabolic flux analyzer. Results We found that miR-1297 was downregulated in OS and that lower expression of miR-1297 promoted proliferation and contributed to the Warburg effect in OS cells. Furthermore, we showed that silencing PFKFB2 inhibited proliferation and reduced aerobic glycolysis while overexpression of PFKFB2 reduced the anti-tumor function of miR-1297 in OS cells. Mechanistically, miR-1297 acted as a tumor suppressor in OS and reduced the expression of PFKFB2 by directly targeting its 3ʹUTR. Conclusion The miR-1297 / PFKFB2 axis regulated OS proliferation by controlling the Warburg effect. Our results revealed a previously undiscovered function of miR-1297 in OS, which strongly linked metabolic alterations with cancer progression. Targeting miR-1297 may become a promising therapeutic approach for OS.

KDM3A-mediated SP1 activates PFKFB4 transcription to promote aerobic glycolysis in osteosarcoma and augment tumor development

“…The aerobic glycolysis is essential to meet the metabolic requirements of cancer cell proliferation [ 9 ]. This is also true for OS cells, since suppression of the glycolytic process has been correlated with blocked tumor growth, survival, and metastasis [ 25 ]. In this research, we confirmed that the KDM3A-SP1 axis-mediated PFKFB4 upregulation promoted aerobic glycolysis in OS and augmented tumor cell growth and metastasis.…”

LINC01123 enhances osteosarcoma cell growth by activating the Hedgehog pathway via the miR‐516b‐5p/Gli1 axis

“…The recently discovered lncRNA LINC01123 was initially identified as an oncogene in non‐small cell lung cancer (NSCLC) 8 . Accumulating evidence indicates that LINC01123 promotes tumor growth in various cancers 6,9 . However, the function of LINC01123 in OS remains unknown.…”

LncRNA HCG18 promotes osteosarcoma growth by enhanced aerobic glycolysis via the miR-365a-3p/PGK1 axis

“…MiRNAs are defined as small endogenous molecules without protein-coding ability and can have an important role in cancer progression [43,44]. For example, miR-1297 was reported to suppress OS proliferation by regulating PFKFB2 [45]. MiR-365a-3p is also a critical participant in regulating cancer growth.…”