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Long non-coding RNA OIP5-AS1 promotes pancreatic cancer cell growth through sponging miR-342-3p via AKT/ERK signaling pathway

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Abstract

Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1), a long non-coding RNA (lncRNA), has been reported to link with the progression of some cancers. However, its biological functions and underlying molecular mechanisms in pancreatic cancer are largely unknown. The aim of this study was to investigate the role of lncRNA OIP5-AS1 in pancreatic cancer. Quantitative real-time PCR analysis revealed that OIP5-AS1 is highly expressed in pancreatic cancer tissues versus adjacent non-tumor tissues. In vitro functional assays showed that downregulation of OIP5-AS1 or overexpression of miR-342-3p inhibited the proliferation, decreased Ki67 expression, and induced cell cycle arrest in pancreatic cancer cells. The expression of cyclinD1, CDK4, and CDK6 was decreased by knockdown of OIP5-AS1. Moreover, we found that OIP5-AS1 acted as a miR-342-3p sponge to suppress its expression and function. Dual-luciferase assay confirmed the interaction of OIP5-AS1 and miR-342-3p and verified anterior gradient 2 (AGR2) as a direct target of miR-342-3p. Results showed that depletion of miR-342-3p abolished the inhibitory effects of OIP5-AS1 knockdown on pancreatic cancer cell growth. The expression of Ki67, AGR2, cyclinD1, CDK4, CDK6, p-AKT, and p-ERK1/2 was reversed by silencing of miR-342-3p in pancreatic cancer cells with OIP5-AS1 knockdown. Further, knockdown of OIP5-AS1 suppressed tumor growth in a xenograft mouse model of pancreatic cancer. OIP5-AS1 induced pancreatic cancer progression via activation of AKT and ERK signaling pathways. Therefore, we demonstrate that OIP5-AS1 functions as oncogene in pancreatic cancer and its downregulation inhibits pancreatic cancer growth by sponging miR-342-3p via targeting AGR2 through inhibiting AKT/ERK signaling pathway.

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Funding

This study was supported by a grant from the Foundation of Department of Science and Technology, Liaoning Province (No. CA19).

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Authors and Affiliations

  1. Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China

    Xiangpeng Meng, Baosheng Wang, Xin Wu & Zhen Liu

  2. Department of Gastrointestinal Endoscopy, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People’s Republic of China

    Jia Ma

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  1. Xiangpeng Meng
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  4. Xin Wu
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Contributions

Zhen Liu contributed to the conception of the study; Jia Ma and Baosheng Wang performed the experiments; Xin Wu performed the data analysis; Xiangpeng Meng drafted and revised the manuscript.

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Correspondence to Zhen Liu.

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All procedures performed in studies involving human participants were in accordance with ethical standards of Shengjing Hospital of China Medical University and with the Declaration of Helsinki and its later amendments or comparable ethical standards. All animal experiments were approved by Institutional Animal Care and Use Committee and performed in accordance with Guide for the Care and Use of Laboratory Animals.

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Key points

•OIP5-AS1 exerts oncogenic function in pancreatic cancer.

•miR-342-3p inhibits the progression of pancreatic cancer.

•OIP5-AS1 acts as a sponge of miR-342-3p in pancreatic cancer.

•AGR2 is a direct target gene of miR-342-3p.

•OIP5-AS1 contributes to pancreatic cancer progression via AKT and ERK pathways.

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Meng, X., Ma, J., Wang, B. et al. Long non-coding RNA OIP5-AS1 promotes pancreatic cancer cell growth through sponging miR-342-3p via AKT/ERK signaling pathway. J Physiol Biochem 76, 301–315 (2020). https://doi.org/10.1007/s13105-020-00734-4

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