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

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单位: [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 [2]Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
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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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出版当年[2019]版:
大类 | 1 区 医学
小类 | 2 区 生化与分子生物学 2 区 细胞生物学 2 区 遗传学 2 区 肿瘤学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 生化与分子生物学 1 区 遗传学 2 区 细胞生物学 2 区 肿瘤学
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出版当年[2018]版:
Q1 ONCOLOGY Q1 GENETICS & HEREDITY Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 CELL BIOLOGY
最新[2023]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 CELL BIOLOGY Q1 GENETICS & HEREDITY Q1 ONCOLOGY

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第一作者单位: [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
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