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Circ_103809 Aggravates the Malignant Phenotype of Pancreatic Cancer Through Modulating miR-197-3p/TSPAN3 Axis

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Abstract

Pancreatic cancer (PC) is a malignant tumor with insidious clinical manifestations and dismal prognosis. Emerging reports have demonstrated that circRNAs exert pivotal biological function in PC. Here, we investigated the crucial biological role and underlying regulatory mechanisms of differentially expressed circ_103809 in PC. In this study, hsa_circ_103809 (hsa_circ_0072088) was identified as the research object via analyzing and screening the aberrantly expressed circRNAs in PC by GSE69362 dataset. The levels of circ_103809 in PC tissues and cells were assessed via qRT-PCR. Functional assays were conducted to monitor the impacts of circ_103809 on PC cells. Additionally, the downstream molecular targets and regulatory networks of circ_103809 were predicted by bioinformatics and validated using luciferase assays and rescue experiments. We found that circ_103809 was substantially upregulated in PC tissues and cells. Silencing circ_103809 restrained the growth viability, clonogenic rate, migration, and invasion capabilities of PC cells. Further mechanistic exploration disclosed that miR-197-3p was the downstream gene of circ_103809, while Tetraspanin-3 (TSPAN3) was a direct target of miR-197-3p. The suppressive effect of circ_103809 knockdown on malignant processes of PC cells was eliminated by miR-197-3p downregulation or TSPAN3 upregulation. Our study demonstrated that circ_103809 served as an innovative positive regulator in the growth and metastasis of PC cells. Furthermore, circ_103809 mediated the miR-197-3p/TSPAN3 axis to modulate the malignant progression of PC cells, which was prospected to be a probable biomarker and an efficient therapeutic target for PC.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Funding

This study was supported by Ningbo Digestive System Cancer Clinical Medicine Research Center (2019A21003), and Medical and Health Science and Technology Program of Zhejiang Province (2023KY239).

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Author notes

  1. Xiang Wu and Shuping Zhou have contributed equally to this work.

Authors and Affiliations

  1. Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Li Huili Hospital, No.1111 Jiangnan Road, Yinzhou District, Ningbo, 315000, Zhejiang, China

    Xiang Wu, Luoluo Wang, Jingyun Ma, Yi Ruan, Xinhua Zhou & Hong Li

  2. Health Science Center, Ningbo University, Ningbo, 315000, Zhejiang, China

    Xiang Wu & Hanjie Shao

  3. Ningbo College of Health Sciences, Ningbo, 315000, Zhejiang, China

    Shuping Zhou

  4. Ningbo Institute of Innovation for Combined Medicine and Engineering, The Affiliated Li Huili Hospital, Ningbo University, Ningbo, 315100, Zhejiang, China

    Yang Zhou

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  1. Xiang Wu
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Contributions

XW and SZ: designed the experiments, and drafted the manuscript. LW and JM: collected the clinical samples and processed statistical data. YR, YZ and HS: performed the experiments and analyzed the data. XZ: designed, and supervised the study. HL: designed, supervised the study and revised the manuscript. All authors read and approved the final version of the manuscript.

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Correspondence to Xinhua Zhou or Hong Li.

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This study was approved by the Ethics Committee of Ningbo Medical Center Li Huili Hospital. Informed consent was obtained from all patients for this study. All experiments were performed in accordance with relevant guidelines and regulations and in compliance with the Declaration of Helsinki.

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Wu, X., Zhou, S., Wang, L. et al. Circ_103809 Aggravates the Malignant Phenotype of Pancreatic Cancer Through Modulating miR-197-3p/TSPAN3 Axis. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00874-0

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