<p>CircRNA Circ_0001721 Promotes the Progression of Osteosarcoma Through miR-372-3p/MAPK7 Axis</p>

Abstract

Background: Osteosarcoma (OS) is the most common bone tumor. Many studies have reported that circular RNAs (circRNAs) play an important role in the development of a variety of human cancers. However, the underlying mechanism of circ_0001721 in regulating osteosarcoma progression remains unknown. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the levels of circ_0001721, miR-372-3p, and mitogen-activated protein kinase 7 (MAPK7) in osteosarcoma tissues and cells. Besides, glycolysis was investigated by glucose consumption, lactate production and hexokinase II (HK2) protein level. Cell proliferation and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry, separately. Cell migration and invasion were determined by transwell assay. Moreover, the protein levels of HK2 and epithelial-to-mesenchymal transition (EMT) markers were determined by Western blot analysis. The relationship between miR-372-3p and circ_0001721 or MAPK7 was predicated by starbase v3.0 and confirmed by dualluciferase reporter assay or RNA binding protein immunoprecipitation (RIP) assay. Murine xenograft model was established to investigate the role of circ_0001721 in vivo. Results: The levels of circ_0001721 and MAPK7 were upregulated in osteosarcoma tissues and cells, while miR-372-3p was downregulated. Knockdown of circ_0001721 inhibited glycolysis, cell proliferation, cell migration, invasion and epithelial-to-mesenchymal transition (EMT), and promoted apoptosis. Circ_0001721 was validated as a sponge of miR-372-3p and mediated glycolysis, cell proliferation, apoptosis, migration, invasion, and EMT of osteosarcoma cells through miR-372-3p. MAPK7 was a target of miR-372-3p and overexpression of MAPK7 attenuated anti-cancer role of miR-372-3p in OS cells. Further studies revealed that circ_0001721 regulates MAPK7 expression via sponging miR-372-3-p. Finally, knockdown of circ_0001721 inhibited tumor progression in vivo. Conclusion: Circ_0001721 promoted osteosarcoma development through the miR-372-3p/ MAPK7 axis.

Tumor Cell-Derived Exosomal Circ-0072088 Suppresses Migration and Invasion of Hepatic Carcinoma Cells Through Regulating MMP-16

“…Of note, circRNAs are closely related to the development of human malignancies. For instance, circ-0001721 accelerates the development of osteosarcoma via the miR-372-3p/MAPK7 axis ( Gao et al, 2020 ), and circRNA circAGFG1 accelerates the progression of triple-negative breast cancer via regulating CCNE1, the sponge of miR-195-5p ( Yang et al, 2019 ). Circ-0072088, also known as circZFR, is a newly discovered circRNA at chr5:32379220-32388780.…”

Tip of the Iceberg: Roles of CircRNAs in Cancer Glycolysis

“…Knockout of Circ_0001721 can inhibit glycolysis, proliferation, and migration of osteosarcoma cells. 95 Under the regulation of PI3K/Akt signaling pathway, the phosphorylation level of glycogen synthase kinase 3β (GSK-3β) decreases, the activity of Akt and ubiquitin ligase changes, and insulin-like growth factor I (IGF-1) Induces the expression of BNIP3, thus affecting the cell cycle and promoting tumor growth. 96 …”

“…Knockout of Circ_0001721 can inhibit glycolysis, proliferation, and migration of osteosarcoma cells. 95 Under the regulation of PI3K/Akt signaling pathway, the phosphorylation level of glycogen synthase kinase 3β (GSK-3β) decreases, the activity of Akt and ubiquitin ligase changes, and insulin-like growth factor I (IGF-1) Induces the expression of BNIP3, thus affecting the cell cycle and promoting tumor growth. 96 In addition, the abnormal expression of circRNA9953-PKN2, circRNA3706-LAMA3, circRNA5431-PRKAA1, circRNA7681-FN1, circRNA8507-LAMC2, circRNA3703-LAMA3, circRNA3341-HSP90AA1, circRNA4628-EGFR, circRNA7574-ITGA6 and circRNA8506-LAMC1 were detected in ESCC.…”

Hsa_circ_0072309 enhances autophagy and TMZ sensitivity in glioblastoma

“…3 Accumulating evidence revealed that circRNAs are associated with the development of many types of cancers. Gao et al 4 reported that circRNA circ_0001721 promotes the progression of osteosarcoma through miR-372-3p/MAPK7 Axis. Fang et al 5 reported that circ_0005075 stimulates the proliferation and metastasis of glioma via downregulating SIRT1.…”