Circ-XPR1 promotes osteosarcoma proliferation through regulating the miR-214-5p/DDX5 axis

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RESEARCH ARTICLE

Circ‑XPR1 promotes osteosarcoma proliferation through regulating the miR‑214‑5p/DDX5 axis Xiaohuan Mao1 · Shuren Guo2,3 · Lan Gao1 · Gang Li1 Received: 9 June 2020 / Accepted: 7 August 2020 © Japan Human Cell Society 2020

Abstract Circular RNAs (circRNAs) are a new class of RNAs that play an important role in the development of various tumors. However, the expression profile and biological function of circRNAs in osteosarcoma (OS) progression remain unclear. OS-related circRNA expression profiles from the GEO database (GSE96964) were downloaded to identify differentially expressed circRNAs between OS and normal tissues. We identified one upregulated circRNA (Circ-XPR1), and RT-PCR was performed to further confirm the expression abundance in OS tissue. Circ-XPR1 was closely related to overall survival and disease-free survival of OS patients. Knockdown of Circ-XPR1 significantly reduced the proliferation of OS cells. Gain- and loss-of-function studies showed that Circ-XPR1 promoted OS cell proliferation by sponging miR-214-5p to regulate DDX5 expression. Our findings suggested that Circ-XPR1 regulates OS cell proliferation by sponging miR-214-5p to regulate DDX5 expression. Therefore, the Circ-XPR1/miR-214-5p/DDX5 axis may serve as a potential therapeutically relevant target for OS. Keywords  Circ-XPR1 · miR-214-5p · DDX-5 · Osteosarcoma

Introduction Osteosarcoma (OS) is the most common malignant tumor of bone and mainly affects children and adolescents [1]. The annual incidence of OS is 4–5 cases per 1,000,000 individuals worldwide [2]. Despite development of OS treatment approaches, such as chemotherapy and curative resection, OS overall survival is poor [3]. The molecular mechanism underlying OS development remains unclear [4]. Therefore, in-depth exploration of the mechanism underlying OS Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1357​7-020-00412​-z) contains supplementary material, which is available to authorized users. * Gang Li [email protected] 1



Department of Clinical Laboratory, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, Henan, People’s Republic of China

2



Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, East Jianshe Road #1, Zhengzhou 450002, Henan, People’s Republic of China

3

Key Clinical Laboratory of Henan Province, Zhengzhou, Henan, People’s Republic of China



development is important to develop effective preventions and therapies. Circular RNAs (circRNAs) are recently identified molecules classified into a type of noncoding RNAs. CircRNAs show diverse biological functions, including cellular proliferation, invasion and metastasis [5]. CircRNAs function by serving as miRNA sponges and subsequently regulating target gene expression [6]. Several studies have explored the role of circRNAs in OS. Fang et al. [7] demonstrated that circ_0000337 is significantly upregulated in OS cell lines and promotes OS progression via the m