CircSAMD4A regulates cell progression and epithelial‑mesenchymal transition by sponging miR‑342‑3p via the regulation of FZD7 expression in osteosarcoma

Abstract

Osteosarcoma (OS) is a primary malignant tumor with a complex etiology. Therefore, research into the pathogenesis of osteosarcoma is considered a priority. circular RNAs play important roles in cell metabolism and in the immune response and are closely associated with cancer treatment. However, research into the association of circular RNAs with osteosarcoma is limited. In the present study, circSAMd4A was validated by RT-qPcR and agarose gel electrophoresis. circSAMd4A and miR-342-3p expression was detected by RT-qPcR. The relative protein expression levels were measured by western blot analysis. MTT assay and flow cytometry were used to detect cell cytotoxicity and apoptosis, respectively. Transwell assay was applied to assess cell migration and invasion. dual-luciferase reporter assay was used to determine the association among circSAMd4A, Frizzled-7 (FZd7) and miR-342-3p. In vivo, subcutaneous tumor formation assay was performed in an experiment with nude mice. The results revealed that the expression levels of circSAMd4A and FZd7 were upregulated, while those of miR-342-3p were downregulated in OS tissues and cells. The inhibition of circSAMd4A suppressed cell progression and epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in OS. The reduction of miR-342-3p reversed the effects of circSAMd4A downregulation on cell cytotoxicity, migration, invasion, apoptosis and EMT in OS, while FZd7 overexpression blocked the effect of miR-342-3p upregulation on OS progression. The suppressive effect of sh-circSAMd4A on tumor growth was thus verified in OS. Overall, the present study demonstrated that circSAMd4A affected cell cytotox-icity, invasion, apoptosis, migration and EMT by regulating the miR-342-3p/FdZ7 axis in OS, thereby providing a novel regulatory mechanism and a potential therapeutic target for OS.

Cancer chemoprevention through Frizzled receptors and EMT

“…Overexpression of FZD7 is associated with EMT in many types of cancer. In melanoma, glioblastoma, and osteosarcoma, FZD7 expression is increased and inhibition of FZD7 suppresses EMT [ 88 , 118 , 119 ]. In cervical cancer, inhibiting FZD7 reverses EMT through decreased MMP2 and MMP9 activity [ 86 ].…”

Circular RNA sterile alpha motif domain containing 4A contributes to cell 5-fluorouracil resistance in colorectal cancer by regulating the miR-545-3p/6-phosphofructo-2-kinase/fructose-2,6-bisphosphataseisotype 3 axis

“…It is a key regulator of cell growth, differentiation, invasion, and drug action, and is involved in tumor development [17]. Xie et al [18] confirmed that circSAMD4A targeted miR-342-3p via the regulation of FZD7 expression to regulate cell progression and epithelial-mesenchymal transition in osteosarcoma. Wei et al [19] proved that circSAMD4A promoted doxorubicin resistance in osteosarcoma cells by regulating the miR-218-5p/KLF8 axis.…”

Understanding Competitive Endogenous RNA Network Mechanism in Type 1 Diabetes Mellitus Using Computational and Bioinformatics Approaches

“…A previous study has reported the oncogene role of circSAMD4A in osteosarcoma. 49 Liu et al found that circSAMD4A acts as an adipogenesis promoting factor. 50 In this study, we found that hsa_circ_0002202 was up-regulated in T1DM PBMCs samples, suggesting that hsa_circ_0002202 may take part in the T1DM procession.…”