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Long noncoding RNA PENG upregulates PDZK1 expression by sponging miR-15b to suppress clear cell renal cell carcinoma cell proliferation

Oncogene volume 39, pages 4404–4420 (2020)Cite this article

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Abstract

PDZK1 downregulation was reported to independently predict poor prognosis of clear cell renal cell carcinoma (ccRCC) patients and induce ccRCC development and progression. However, the underlying mechanism of PDZK1 downregulation remains unknown. Competing endogenous RNA (ceRNA) networks are emerging as new players in gene regulation and are associated with cancer development. ceRNAs regulate other RNA transcripts by competing for shared miRNAs. To investigate the role and mechanism of ceRNAs in PDZK1 downregulation and the development of ccRCC, we searched databases for miRNAs and lncRNAs that regulate PDZK1 expression in ccRCC tissues and assessed their effects in ccRCC. We found that miR-15b was expressed at higher levels in ccRCC tissues, and its upregulation was clinically associated with lower PDZK1 level, larger tumor size and shorter survival time of ccRCC patients. Conversely, a novel lncRNA (lncPENG) was expressed at a lower level in ccRCC tissues, and its downregulation was associated with the same effects as upregulation of miR-15b. Downregulation of miR-15b and upregulation of lncPENG resulted in a significant increase in PDZK1 level and inhibition of proliferation in vitro and in vivo. Mechanistically, lncPENG directly bound to miR-15b and effectively functioned as a sponge for miR-15b to modulate the expression of PDZK1. Thus, lncPENG may function as a ceRNA to attenuate miR-15b-dependent PDZK1 downregulation and inhibit cell proliferation, suggesting that it may be clinically valuable as a therapeutic target and a prognostic biomarker of ccRCC.

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Fig. 1: miR-15b targets PDZK1 and is associated with proliferation and prognosis in ccRCC.
Fig. 2: miR-15b inhibits the expression of target gene PDZK1.
Fig. 3: miR-15b promotes proliferation of ccRCC cells in vitro and in vivo by inhibiting PDZK1 expression.
Fig. 4: lncPENG as a possible RNA competing with the PDZK1 mRNA correlates with prognosis of ccRCC and upregulates PDZK1 expression.
Fig. 5: lncPENG inhibits proliferation of ccRCC cells in vitro and in vivo via upregulating PDZK1 expression.
Fig. 6: lncPENG acts as a ceRNA directly binding to miR-15b.
Fig. 7: lncPENG regulates miR-15b/PDZK1-mediated proliferation of ccRCC cells via ceRNA mechanism.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of the People’s Republic of China (Nos. 81672521, 81974415, 81372739) and the Natural Science Foundation of Beijing (No. 7192021).

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  1. These authors contributed equally: Yijun Qi, Yuanzhen Ma

Authors and Affiliations

  1. Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China

    Yijun Qi, Yuanzhen Ma, Zhiqiang Peng, Lanxin Li, Yilan Tang, Junqi He & Junfang Zheng

  2. Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Lei Wang

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Qi, Y., Ma, Y., Peng, Z. et al. Long noncoding RNA PENG upregulates PDZK1 expression by sponging miR-15b to suppress clear cell renal cell carcinoma cell proliferation. Oncogene 39, 4404–4420 (2020). https://doi.org/10.1038/s41388-020-1297-1

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