<p>Antitumor Effect of miR-1294/Pyruvate Kinase M2 Signaling Cascade in Osteosarcoma Cells</p>

Abstract

Background: MicroRNAs (miRNAs) can act as negative regulators of gene expression, and play a crucial role in cancer progression. The aim of this study was to investigate the role of miR-1294/pyruvate kinase M2 (PKM2) axis in osteosarcoma cells in vitro and in vivo. Methods: The function of miR-1294 and its association with PKM2 in osteosarcoma cells were studied by real-time PCR, CCK-8, Western blot, scratch test, transwell assay, flow cytometry, and dual-luciferase reporter assays. The effect of miR-1294 on tumor growth in vivo was evaluated in a subcutaneous xenograft model of osteosarcoma. Results: miR-1294 was downregulated in osteosarcoma cells. Forced overexpression of miR-1294 inhibited cell proliferation, migration, and invasion, and induced G0/G1 arrest and apoptosis. Consistently, protein expression levels of proliferating cell nuclear antigen, c-Myc, cyclin D1, active matrix metalloproteinase 2, and active matrix metalloproteinase 9 were decreased, and cleaved caspase 3 and cleaved PARP were increased following miR-1294 overexpression. Moreover, we demonstrated that PKM2 was a target of miR-1294 in osteosarcoma cells, and the effects caused by miR-1294 mimic were reversed by the overexpression of PKM2. Furthermore, we found that upregulation of miR-1294 inhibited tumorigenesis of osteosarcoma cells in vivo, which was accompanied by downregulation of PKM2. Conclusion: Our results revealed that miR-1294/PKM2 signaling cascade exerts important roles in the regulation of tumor progression, implying that this pathway may serve as a potential therapeutic target in osteosarcoma.

Oxygen sensing, mitochondrial biology and experimental therapeutics for pulmonary hypertension and cancer

“…PKM2 synthetic peptide aptamers and small molecules targeting PKM2 have also been shown to reduce the growth of tumor cells [174,202], indicating the pathologic role of the PKM2 isoform in cancer cells. Overexpression of miR-1294, which inhibits PKM2 expression, inhibits cell proliferation, migration, and invasion, and induces apoptosis in osteosarcoma cells [203]; however, miRs have many targets and this miR intervention would not selectively target PKM2. Increased expression of the PKM2 tetramer, which is the active form of PKM2, inhibits glycolysis and promotes glucose oxidation [204].…”

LncCCAT1 interaction protein PKM2 upregulates SREBP2 phosphorylation to promote osteosarcoma tumorigenesis by enhancing the Warburg effect and lipogenesis

“…Previous studies have shown that PKM2 is correlated with the Enneking stage and distant metastasis in OS, and it has been identified as an independent prognostic factor for lethal disease (13)(14)(15)18,42). These studies revealed that PKM2 may represent a new therapeutic target for OS.…”

“…Another study confirmed that metformin increased the sensitivity of OS stem cells to cisplatin by inhibiting the expression of PKM2 (14). The miR-1294/PKM2 signaling cascade plays important roles in the regulation of OS progression (15). Through direct binding to specific sequence element(s), RNA binding proteins (RBPs) play a pivotal role in co-and post-transcriptional RNA regulatory events (16).…”

“…Genetic alteration and epigenetic modification of PKM2 lead to dysregulation of tumor-associated genes, which finally results in tumor progression (45). Previous studies have reported that PKM2 can be translocated into the nucleus of tumor cells via a variety of mechanisms, which subsequently interact with the molecules responsible for cell proliferation, invasion, and metastasis (15,18,46).…”

Exosomal circSHKBP1 participates in non-small cell lung cancer progression through PKM2-mediated glycolysis

“…miR-1294 was predicted to be a cotarget for circSHKBP1 and PKM2 through an online database and article. 21 miR-1294 was found to be downregulated, while PKM2 was upregulated in 30 NSCLC tissues with high levels of circSHKBP1 (Figures S3A and S3B). Furthermore, we found that the expression of miR-1294 was negatively associated with the expression of circSHKBP1, and that the expression of PKM2 was positively associated with the expression of circSHKBP1 (Figures S3C and S3D).…”