The Roles of Circular RNAs in Osteosarcoma

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Abstract

Osteosarcoma is a malignant tumor that occurs most commonly in the metaphysis of the long bones in the limbs in children and adolescents. Even with surgery and neoadjuvant chemotherapy, the therapeutic effect has reached a peak with 60–70% survival rates. Therefore, new biological targets or molecular mechanisms that enhance the efficacy of osteosarcoma treatments are needed. Circular RNAs (circRNAs) are useful biomarkers that have recently been recognized clinically and in medical research and have been of interest due to the use of next-generation sequencing and bioinformatics analysis. CircRNAs are involved in many diseases, including cancer. Therefore, this review aims to summarize the roles of circRNA in the diagnosis, progression, and prognosis of osteosarcoma.

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Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1

Zhu Kun-Peng, Ma Xiao-Long, Zhang Chun-Lin (2018)

Circular RNAs (circRNAs) represent a widespread class of non-coding RNAs generated from back-splicing, with a circular loop structure. Many circRNAs have been reported to play essential roles in cancer development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNA in osteosarcoma (OS) remains largely unknown. In the current study, we examined the expression level of circular RNA PVT1 (circPVT1), previously screened and identified the oncogenic role in gastric cancer, in OS and found that circPVT1 was significantly up-regulated in the OS tissues, serums and chemoresistant cell lines, correlated with poor prognosis of OS patients. Besides, ROC curve demonstrated that circPVT1 may be a better diagnostic biomarker than alkaline phosphatase (ALP) in OS with more sensitivity and specificity. In addition, functional assays revealed that circPVT1 knockdown by siRNA could weaken the resistance to doxorubicin and cisplatin of OS cells through decreasing the expression of classical drug resistance-related gene ABCB1. These findings may provide a new insight into the role of circPVT1 as a biomarker for the diagnosis and treatment target of OS.

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CircFAT1 sponges miR-375 to promote the expression of Yes-associated protein 1 in osteosarcoma cells

Gang Liu, Kangmao Huang, Zhiwei Jie … (2018)

Background There is an urgent need to identify new molecular targets for treatment of osteosarcoma. Circular RNAs are a class of endogenous RNAs that are extensively found in mammalian cells and exert critical functions in the regulation of gene expression, but in osteosarcoma the underlying molecular mechanism of circular RNAs remain poorly understood. Here we assessed the tumorigenesis properties of a circular RNA, circFAT1 in osteosarcoma. Methods The effects of circFAT1/miR-375/YAP1 was evaluated on human osteosarcoma cells growth, apoptosis, migration, invasion and tumorigenesis. Signaling pathways were analyzed by western blotting, qRT-PCR, fluorescence in situ hybridization, chromogenic in situ hybridization,RNA Binding Protein Immunoprecipitation and immunofluorescence. The consequence of circFAT1 short hairpin RNA combined or not with miR-375 sponge was evaluated in mice bearing 143B xenografts on tumor growth. Results In this study, we observed significant upregulation of circFAT1 originating from exon 2 of the FAT1 gene in human osteosarcoma tissues and cell lines. Inhibition of circFAT1 effectively prevented the migration, invasion, and tumorigenesis of osteosarcoma cells in vitro and repressed osteosarcoma growth in vivo. Mechanistic studies revealed that circFAT1 contains a binding site for the microRNA-375 (miR-375) and can abundantly sponge miR-375 to upregulate the expression of Yes-associated protein 1. Moreover, inhibition of miR-375 reversed attenuation of cell proliferation, migration, and invasion, which was induced by circFAT1 knockdown, and therefore promoted tumorigenesis. Conclusions Our findings demonstrate a novel function of circFAT1 in tumorigenesis and suggest a new therapeutic target for the treatment of osteosarcoma. Electronic supplementary material The online version of this article (10.1186/s12943-018-0917-7) contains supplementary material, which is available to authorized users.

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Increased circular RNA UBAP2 acts as a sponge of miR-143 to promote osteosarcoma progression

Hao Zhang, Guangchao Wang, Chen Ding … (2017)

Deregulated expression of circular RNA (circRNA) has been determined to be important in carcinogenesis and progression; however, in the most common type of primary malignant bone tumor osteosarcoma, the roles of circRNA in cancer development still remain to be elucidated. Here, we found that circRNA UBAP2 (circUBAP2) expression is significantly increased in human osteosarcoma tissues as compared to those in matched controls. Increased circUBAP2 expression was significantly correlated with human osteosarcoma progression and prognosis. Furthermore, increased circUBAP2 could promote osteosarcoma growth and inhibit apoptosis both in vitro and in vivo. Mechanistically, circUBAP2 was found to inhibit the expression of microRNA-143 (miR-143), thus enhancing the expression and function of anti-apoptotic Bcl-2, which is a direct target of miR-143. Together, our results suggest the roles of circUBAP2 in osteosarcoma development and implicate its potential in prognosis prediction and cancer therapy.

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Journal

Journal ID (nlm-ta): Med Sci Monit

Journal ID (iso-abbrev): Med. Sci. Monit

Journal ID (publisher-id): Medical Science Monitor

Title: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research

Publisher: International Scientific Literature, Inc.

ISSN (Print): 1234-1010

ISSN (Electronic): 1643-3750

Publication date Collection: 2019

Publication date (Electronic): 25 August 2019

Volume: 25

Pages: 6378-6382

Affiliations

Department of Orthopedics, The Second Hospital of Anhui Medical University, Hefei, Anhui, P.R. China

Author notes

Corresponding Author: Jun Li, e-mail: efylijunpaper@ 123456163.com

[A]

Study Design

[B]

Data Collection

[C]

Statistical Analysis

[D]

Data Interpretation

[E]

Manuscript Preparation

[F]

Literature Search

[G]

Funds Collection

[*]

Yong Zhang and Jiale Li contributed equally to this work

Article

Publisher ID: 915559

DOI: 10.12659/MSM.915559

PMC ID: 6724563

PubMed ID: 31446435

SO-VID: 163ad9c9-9b23-4952-85df-dcb62cd2ed2f

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This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

The Roles of Circular RNAs in Osteosarcoma

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Most cited references 23

Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1

CircFAT1 sponges miR-375 to promote the expression of Yes-associated protein 1 in osteosarcoma cells

Increased circular RNA UBAP2 acts as a sponge of miR-143 to promote osteosarcoma progression

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