Hsa_circ_0008259 modulates miR-21-5p and PDCD4 expression to restrain osteosarcoma progression

Abstract

Background: Osteosarcoma (OS) is one of the most common primary bone tumors in children and adolescents. However, the molecular mechanism of OS tumorigenesis is still little known. Circular RNA (circRNA) is a key player in the progression of many cancers. This study is performed to decipher the role and mechanism of circ_0008259 in the progression of OS. Methods: A differentially expressed circRNA, circ_0008259, was screened out by analyzing the expression profile of circRNA in OS tissue. Circ_0008259, miR-21-5p and programmable cell death 4 (PDCD4) mRNA expression levels in OS tissues and cells were detected by qRT-PCR. Cell viability, metastatic potential and apoptosis were evaluated by cell counting kit-8 assay, Transwell and flow cytometry. The targeting relationship between circ_0008259 and miR-21-5p, and miR-21-5p and PDCD4 mRNA was analyzed and probed by bioinformatics analysis and dual-luciferase reporter assay, RNA-binding protein immunoprecipitation assay and RNA-pull down assay. The regulatory effects of circ_0008259 and miR-21-5p on PDCD4 protein expression in OS cells were detected by Western blot assay. Results: Circ_0008259 expression and PDCD4 expression were down-regulated and miR-21-5p expression was elevated in the OS tissues and cells. Functional experiments showed that circ_0008259 overexpression significantly inhibited the proliferation and metastatic potential of OS cells and promoted the apoptosis. Besides, PDCD4 was validated as the target gene of miR-21-5p, and circ_0008259 could competitively bind to miR-21-5p, thus up-regulating PDCD4 expression in OS cells. Conclusions: Circ_0008259 suppresses OS progression via regulating miR-21-5p/PDCD4 axis.

Circ_0051079 functions as an oncogenic regulator in osteosarcoma by leading to MAFB expression upregulation by competitively interacting with miR-1286

“…Moreover, circ_0051079 was identified to regulate MAFB expression via targeting miR-1286 in OS cells. Circ_0008259 was found to inhibit OS progression by upregulation of miR-21-5p-related PDCD4 [ 8 ]. Furthermore, hsa_circ_0000006 enhanced OS tumorigenesis through sequestering miR-361-3p and increasing LRIG1 expression [ 36 ].…”

“…CircRNAs can serve as miRNA sponges to induce gene regulation at post-transcriptional levels, further affecting cancer initiation and development, including OS [ 7 ]. For instance, circ_0008259 might increase PDCD4 level via competitively binding to miR-21-5p, thus delaying cell proliferation and metastatic potential in OS [ 8 ]. In addition, Zhang et al elucidated that circ_0051079 facilitated OS proliferation and metastasis through mediating the miR-26a-5p/TGF-β1 axis [ 9 ].…”

Emerging role of mesenchymal stem/stromal cells (MSCs) and MSCs-derived exosomes in bone- and joint-associated musculoskeletal disorders: a new frontier

“…PDCD4 down-regulates various survival and proliferation involved signaling axis, like the MAPK axis, thus compromising the expansion and growth of the osteoblast [ 193 ]. Although it acts as a tumor suppressor in osteosarcoma [ 194 ], elevated levels of the PDCD4 may stall bone repair due to its suppressive effects on multiple axes.…”

Circ_001422 aggravates osteosarcoma progression through targeting miR-497-5p/E2F3 axis

“…As an important participant in the ceRNA network, circRNAs can adsorb miRNAs through sponges, thereby affecting the latter downstream target gene levels, resulting in changes in cell phenotypes [12][13][14] . Here, we have demonstrated miR-497-5p as circ_001422's target, while E2F3 as miR-497-5p's target.…”