The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression
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Cancer Cell International Open Access
PRIMARY RESEARCH
The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression Feng Pan1,2 , Jun Zhang2, Benseng Tang2, Li Jing2, Bing Qiu2* and Zhengang Zha1*
Abstract Background: Recently, it has been demonstrated that circular RNA (circRNA) contributes to the production and progression in human cancer. However, the specific function and underlying mechanism of circ_0028171 in osteosarcoma (OS) still remain largely unclear and require to be investigated. Methods: In our study, we confirmed differentially expressed circRNAs by microarray analysis in normal bone cells vs. OS cell lines. The expression of circ-0028171 in OS was measured by qRT-PCR. Nuclear-cytoplasmic fractionation was employed to identify the localization of circ-0028171, and RNase R and actinomycin D treatment were used to prove its circular characteristic. In vitro experiments, such as CCK-8 method, cell count, cell colony formation, transwell migration and invasion assays, and in vivo tumor models were adopted to evaluate the effect of circ_0028171. Further, luciferase reporter, RIP and RNA pull-down assays were conducted to confirm the binding sites of circ_0028171 with miR-218-5p. Results: We found that circ_0028171 displayed a remarkably higher expression in both OS tissues and cell lines. Circ_0028171 mainly located in the cytoplasm as a stable cyclic transcript. Knockdown of circ_0028171 suppressed OS tumor growth in vitro and in vivo, while up-regulated circ_0028171 remarkably enhanced cell proliferation, migration and invasion abilities in OS. Several mechanistic experiments revealed that circ_0028171 served as a sponge of miR-218-5p to increase IKBKB expression. Conclusions: our research reveals that circ_0028171 might promote the malignant behavior of OS tissues through miR-218-5p/IKBKB axis, which could be a potential novel marker for early diagnosis of OS. Keywords: Circ_0028171, miR-218-5p, IKBKB, osteosarcoma, growth, metastasis Background Osteosarcoma (OS) is the third prevalent and lethal malignant bone tumor among children and adolescents. A great number of cancer-related deaths are caused by Osteosarcoma annually due to its fast proliferation, high metastatic properties, and chemo-resistance [1, 2]. In recent years, a wide variety of medical therapies have been proposed for Osteosarcoma, including surgery, *Correspondence: [email protected]; [email protected] 1 Department of Bone and Joint Surgery, Institute of Orthopedic Diseases, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China 2 Department of Bone and Joint Surgery, Gui Zhou Orthopedic Hospital, Gui Zhou, China
chemotherapy, radiotherapy, hormonotherapy, and small molecular targeting treatments. Indeed, we have obtained promising results, as previously reported, the prognosis of OS patients without metastasis is generally excellent, and the five-year survival is greater than 60% [3]. Nevertheless, the prognosis of patients with advanced disease is very poor because of the recurre
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