METTL3-mediated m6A modification of circRNF220 modulates miR-330-5p/survivin axis to promote osteosarcoma progression

Abstract

Background Circular RNAs (circRNAs) play a crucial role in regulating various physiological processes. However, the precise regulatory mechanisms of circRNF220s in osteosarcoma (OS) are not well understood. Methods The abundances of circRNF220, miR-330-5p, and survivin were determined using qRT-PCR. To assess the m6A accumulation in circRNF220, a methylated RNA immunoprecipitation (Me-RIP) assay was conducted. Cellular multiplication, motility, and invasion were examined using the cell Counting Kit-8 (CCK-8), EdU, colony formation, Transwell, and wound-healing assays. The binding relationships were measured through RNA immunoprecipitation (RIP) and luciferase reporter assays. In vivo functionality was assessed using xenograft models. Results CircRNF220 was identified as being overexpressed in both OS cells and tissues. In vitro experiments demonstrated that silencing circRNF220 impeded the proliferation, invasion, and motility of OS cells. Similarly, in vivo studies confirmed that downregulating circRNF220 inhibited the growth of OS. Further mechanistic investigations unveiled that METTL3-modulated circRNF220 regulated the progression of OS by upregulating survivin expression through acting as a sponge for miR-330-5p. Conclusion The modulation of METTL3-regulated circRNF220 has been found to promote the progression of OS by modulating the miR-330-5p/survivin axis. This novel finding suggests a potentially unique approach to managing OS.

Circular RNA circLIFR suppresses papillary thyroid cancer progression by modulating the miR-429/TIMP2 axis

“…PTC is the predominant endocrine tumor and has become a significant health concern (Chen et al 2023 ). Previous evidence has highlighted the pivotal role of circRNA in the pathogenesis of various ailments, including cancer (Liu et al 2019 , 2023a , b ; Huang et al 2023 ; Chen 2020 ). Our study is the first to demonstrate the tumor-suppressive role of circLIFR in PTC.…”

N6-methyladenosine methylation analysis of circRNAs in acquired middle ear cholesteatoma

“…Specifically, among these 3,755 circRNAs, 3,742 exhibited hypermethylation while 13 showed hypomethylation ( Figure 1 ). Accumulating evidence has shown that aberrant m6A modification of circRNAs contribute to the development of various diseases, including hepatocellular carcinoma ( Chen et al, 2022 ), innate immune system inhibition ( Chen et al, 2019 ), osteosarcoma ( Liu et al, 2023 ) and age-related cataract progression ( Li et al, 2023 ). These suggest that the m6A-modification patterns of circRNA found in our study may play a significant role in the pathogenesis of middle ear cholesteatoma.…”

Recent advances of m6A methylation in skeletal system disease

“…Furthermore, evidence have shown that circRNF220 and circNRIP1 are identified as oncogenic roles in OS progression via METTL3 methylation. And METTL3-induced circRNF220 and circNRIP1 promote OS proliferation, invasion by modulating miR-330-5p/survivin axis or sponging miR-199a respectively [ 160 , 168 ]. In addition, targeting the METTL3/ZBTB7C axis, METTL3/USP13/ATG5 axis, METTL3/COPS5 axis, METTL3/LEF1/ Wnt/β-catenin axis, METTL3/TRAF6 axis and METTL3/HDAC5/miR-142-5p/ARMC8 axis may help to understand OS pathogenesis and develop the novel strategies for OS therapy [ 161 , 163 , 164 , 166 , 167 , 172 ].…”

“…Proliferation, migration, invasion and metastasis are the main biological processes of OS, of which the underlying mechanisms may help to understand the pathogenesis and prognosis of OS [199]. It is reported that METTL3 plays an essential role in promoting OS progression by cooperating with noncoding RNAs, circRNAs and other targets [159][160][161]. For example, Zhang et al found that METTL3 promoted the proliferation and migration of OS via increasing the stability of MALAT1 [159].…”