circRNA_PTPRA functions as a sponge of miR‑582‑3p to regulate hepatocellular carcinoma cell proliferation, migration, invasion and apoptosis

Jin,Yanlin; Zhang,Yi; Luo,Xiaoming

doi:10.3892/etm.2021.10711

circRNA_PTPRA functions as a sponge of miR‑582‑3p to regulate hepatocellular carcinoma cell proliferation, migration, invasion and apoptosis

Authors:
- Yanlin Jin
- Yi Zhang
- Xiaoming Luo
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Affiliations: First Ward of General Surgery, Railway Hospital, Shaoguan, Guangdong 512000, P.R. China, Public Health Guidance Section, Hongshan Centre for Diseases Control and Prevention, Wuhan, Hubei 430070, P.R. China, Department of Hepatobiliary Gastrointestinal Surgery, Hubei No. 3 People's Hospital of Jianghan University, Wuhan, Hubei 430033, P.R. China
Published online on: September 8, 2021 https://doi.org/10.3892/etm.2021.10711
Article Number: 1276
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) is a lethal disease and one of the most common types of cancer. HCC is associated with exponentially increasing morbidity and mortality rates. Accumulating evidence has identified circular RNAs (circRNAs) to be regulators of cancer progression. However, to the best of our knowledge, the potential effect of circRNA protein tyrosine phosphatase receptor type A (circRNA_PTPRA) in HCC and its mechanism remain unknown. The present study aimed to assess the effects and underlying mechanism of circRNA_PTPRA in a HCC Huh‑7 cells model. The sites of interaction between circRNA_PTPRA and microRNA (miR)‑582‑3p were predicted using the StarBase software and verified using dual luciferase reporter and RNA immunoprecipitation (RIP) assays in Huh‑7 cells. HCC cell viability, apoptosis, migration and invasion were measured using MTT, ﬂow cytometry and Transwell assays, respectively. The expression levels of circRNA_PTPRA, miR‑582‑3p, cyclin D1, MMP‑9, Bcl‑2 and Bax were analyzed using reverse transcription‑quantitative PCR and western blotting. The results of the dual luciferase reporter and RIP assays demonstrated that miR‑582‑3p directly targeted circRNA_PTPRA. Compared with the human normal hepatocyte cell line, THLE‑2, the expression levels of circRNA_PTPRA were upregulated, which were found to be inversely correlated with those of miR‑582‑3p expression in Huh‑7 and HCCLM3 cells. miR‑582‑3p overexpression using mimics suppressed cell proliferation, migration and invasion, whilst downregulating cyclin D1 and MMP‑9 expression in Huh‑7 cells. In addition, transfection of HCC cells with the miR‑582‑3p mimic promoted apoptosis by downregulating Bcl‑2 expression and upregulating Bax expression in Huh‑7 cells. Knocking down circRNA_PTPRA expression using small interfering RNA (siRNA) markedly downregulated circRNA_PTPRA expression levels and upregulated miR‑582‑3p expression, but was reversed by co‑transfection with the miR‑582‑3p inhibitor. Furthermore, reduced HCC cell proliferation, migration and invasion, increased levels of cell apoptosis, upregulated Bax expression and downregulated cyclin D1, MMP‑9 and Bcl‑2 expression were all observed after knocking down circRNA_PTPRA. All these effects aforementioned were reversed by co‑transfection with the miR‑582‑3p inhibitor. In conclusion, findings from the present study suggested that circRNA_PTPRA may regulate HCC cell proliferation, invasion, apoptosis and migration by sponging miR‑582‑3p. This indicates that the circRNA_PTPRA/miR‑582‑3p axis may represent a potential target for HCC diagnosis and treatment.

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