Circular RNA circUBAP2 regulates proliferation and invasion of osteosarcoma cells through miR-641/YAP1 axis

Abstract

Background: Osteosarcoma (OS) is a common malignant bone cancer and is still a growing threat to young people. Circular RNAs (CircRNAs) are reported to be involved in the development of diverse human cancers. However, the role of circUBAP2 in OS progression is rarely reported. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression levels of circUBAP2 and miR-641 in OS tissues and cells. Cell Counting Kit-8 (CCK-8) assay was employed to check cell proliferation. The ability of cell invasion was evaluated by transwell assay. The protein levels of E-cadherin, Vimentin and Yes-associated protein 1 (YAP1) were measured by western blot. The starBase was used to predict binding sites between miR-641 and circUBAP2 or YAP1 and the dual-luciferase reporter assay was performed to verify the interaction. Results: The level of circUBAP2 was significantly upregulated in OS tissues and cells compared with normal tissues and cells, which was contrary to the expression of miR-641. Downregulation of circUBAP2 suppressed proliferation and invasion of OS cells and weakened the process of epithelial-mesenchymal transition (EMT). Moreover, miR-641 was a target of circUBAP2 and could bind to the 3′-untranslated region (3′UTR) of YAP1. In addition, overexpression of circUBAP2 or YAP1 reversed the inhibitory effects of miR-641 on proliferation and invasion of OS cells. Further research indicated that circUBAP2 regulated the expression of YAP1 by interacting with miR-641 in OS cells. Conclusion: Knockdown of circUBAP2 impeded proliferation and invasion of OS cells by downregulating the expression of YAP1 via sponging miR-641.

Cancer-associated fibroblast-derived CXCL11 modulates hepatocellular carcinoma cell migration and tumor metastasis through the circUBAP2/miR-4756/IFIT1/3 axis

“…circUBAP2 modulates pancreatic adenocarcinoma tumorigenesis by regulating the levels of hsa-miR-494 and the expression of CXCR4, HIF1A, ZEB1, SDC1, and TWIST1 32 . In addition, circUBAP2 modulates cancer cell malignancy through the miR-641/YAP1 axis and miR-361-3p/SOX4 axis in osteosarcoma and cervical cancer, respectively 33 , 34 . Consistently, our results showed that circUBAP2 silencing was sufficient to attenuate HCC cell migration, as well as the promotive effects of CXCL11 on HCC cell migration.…”

<p>TRPS1 and YAP1 Regulate Cell Proliferation and Drug Resistance of Osteosarcoma via Competitively Binding to the Target of circTADA2A – miR-129-5p</p>

“…For example, YAP1 knockdown inhibited OS cell proliferation in vitro and in vivo. [19][20][21][22] In addition, upregulation of YAP1 promoted OS cell proliferation, migration, and invasion, thereby leading to tumorigenesis. 23 TRPS1 is also generally overexpressed in multiple types of cancer [11][12][13]24,25 and our previous study has confirmed its role in enhancing drug resistance in OS cells.…”

CircRNA–miRNA networks in regulating bone disease

“…For example, a dual‐luciferase reporter assay shows circRNA UBAP2 is can bind to miR‐641 (Gong et al 2020a,b), which can decrease the expression of YAP1 (H. Wu et al, 2020), a transcriptional co‐activator involved in cancer progression (Vincent‐Mistiaen et al, 2018). Transfection experiment shows overexpression YAP1 will enhance the proliferation and invasion ability of OS cells (G. Liu et al, 2018), reversing E‐cadherin and Vimentin protein levels of miRNA‐641 group (H. Wu et al, 2020) as well. Besides this, sponged by circRNA UBAP2, miR‐506‐3p is reported to work as an inhibitor of SEMA6D (Gong et al 2020a,b), which functions as an oncogene in OS with the ability to promote the proliferation, invasion, and migration of OS cells (Kansara et al, 2014).…”