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Circ_0075804 promotes the malignant behaviors of retinoblastoma cells by binding to miR-138-5p to induce PEG10 expression

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Abstract

Background

It has been gradually recognized that circular RNAs (circRNAs) are important modulators in multiple malignancies. Here, we analyzed the function of circ_0075804 and explored its associated mechanism in regulating retinoblastoma (RB) progression.

Methods

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were utilized to measure RNA and protein expression, respectively. Cell proliferation was analyzed by Cell counting kit-8 (CCK8) assay and 5-Ethynyl-2’-deoxyuridine (EdU) assay. Cell apoptosis was assessed by flow cytometry. Cell migration and invasion abilities were analyzed by wound healing assay and transwell invasion assay. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to verify intermolecular target relations. Xenograft tumor model was used to analyze the role of circ_0075804 in tumor growth in vivo.

Results

Circ_0075804 expression was markedly up-regulated in RB tissues and cell lines. Circ_0075804 knockdown restrained the proliferation, migration and invasion whereas promoted the apoptosis of RB cells. Circ_0075804 acted as a molecular sponge for microRNA-138-5p (miR-138-5p), and circ_0075804 silencing-induced effects were partly reversed by miR-138-5p knockdown in RB cells. MiR-138-5p interacted with the 3’ untranslated region (3’UTR) of paternally expressed 10 (PEG10). Circ_0075804 positively regulated PEG10 level by sponging miR-138-5p in RB cells. PEG10 overexpression largely overturned miR-138-5p overexpression-mediated effects in RB cells. Circ_0075804 knockdown blocked xenograft tumor growth in vivo.

Conclusion

Circ_0075804 promoted RB progression via miR-138-5p-dependent regulation of PEG10, which provided new insight in RB therapy.

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Data availability

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Funding

This work was supported by Social Science Project in Longhua District(Basic Research Program)(No. 10162A20190729B559B3B) and Shenzhen Science and Technology (No. JCYJ20190812155213250).

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Authors and Affiliations

  1. Department of Ophthalmology, Shenzhen Eye Hospital, Shenzhen Eye Institute, Jinan University, No. 18 Zetian Road, Futian District, Shenzhen, 518040, Guangdong Province, China

    Yanling Zhang

  2. Department of Ophthalmology, The Second People’s Hospital of Shenzhen, Shenzhen, Guangdong Province, China

    Xiaoyan Dou & Qinghui Kong

  3. Department of Ophthalmology, School of Medical Technology and Nursing, Shenzhen Polytechnic, Shenzhen, Guangdong Province, China

    Yuying Li

  4. Department of Ophthalmology, Shenzhen Longhua District Maternity & Child Healthcare Hospital, Shenzhen, Guangdong Province, China

    Xing Zhou

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  1. Yanling Zhang
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  2. Xiaoyan Dou
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  3. Qinghui Kong
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  4. Yuying Li
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  5. Xing Zhou
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Contributions

YZ was responsible for drafting the manuscript. YZ and XD contributed to the analysis and interpretation of data. QK, YL and XZ contributed in the data collection. All authors read and approved the final manuscript.

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Correspondence to Yanling Zhang.

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The authors declare that they have no conflicts of interest.

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Written informed consent was obtained from patients with approval by the Institutional Review Board in Shenzhen Eye Hospital, Shenzhen Eye Institute, Jinan University.

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Zhang, Y., Dou, X., Kong, Q. et al. Circ_0075804 promotes the malignant behaviors of retinoblastoma cells by binding to miR-138-5p to induce PEG10 expression. Int Ophthalmol 42, 509–523 (2022). https://doi.org/10.1007/s10792-021-02067-7

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  • DOI: https://doi.org/10.1007/s10792-021-02067-7

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