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Long noncoding RNA DANCR contributes to docetaxel resistance in prostate cancer through targeting the miR-34a-5p/JAG1 pathway

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机构: [1]Hebei Med Univ, Dept Urol Surg, Hosp 4, 12 Jiankang Rd, Shijiazhuang 050011, Hebei, Peoples R China
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关键词: DANCR miR-34a-5p JAG1 docetaxel resistance prostate cancer

摘要:
Background: Chemotherapy is one of the available options for prostate cancer (PC). However, the acquisition of chemoresistance has become a major cause of chemotherapy failure. The long noncoding RNA DANCR is demonstrated to serve as an oncogene in various human cancers, including PC. However, the potential role of DANCR in docetaxel (DTX) resistance of PC and its underlying mechanism remains unclear. Methods: The abundance of DANCR, miR-34a-5p, and JAG1 mRNA was examined by quantitative reverse transcription PCR. The Cell Counting Kit-8 (CCK8) was used to determine the 50% inhibitory concentration value. Cell viability was evaluated by CCK8 and colony-formation assays. Transwells were utilized to analyze cell migration and invasion ability. The protein levels of LRP, P-gp, MRP1, and JAG1 were measured by Western blot assay. The target relationship between DANCR and miR-34a-5p, as well as miR-34a-5p and JAG1, was demonstrated by dual-luciferase, RNA immunoprecipitation, and RNA pull-down analysis. Tumor xenograft was undertaken to confirm the effect of DANCR on DTX resistance in PC. Results: DANCR and JAG1 were significantly upregulated, but miR-34a-5p was down-regulated in DTX-resistant PC. Silencing of DANCR improved the DTX efficacy in DTX-resistant PC cells. DANCR served as a competing endogenous RNA of miR-34a-5p, leading to the derepression of miR-34a-5p target JAG1, which eventually triggered the resistance to DTX in DTX-tolerated PC. Conclusion: The DANCR/miR-34a-5p axis enhanced DTX resistance of PC via targeting JAG1, providing a novel insight to improve chemotherapy for PC.

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出版当年[2019]版:
大类 | 3 区 医学
小类 | 3 区 生物工程与应用微生物 4 区 肿瘤学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 生物工程与应用微生物 4 区 肿瘤学
JCR分区:
出版当年[2019]版:
Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q2 ONCOLOGY
最新[2023]版:
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q3 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [1]Hebei Med Univ, Dept Urol Surg, Hosp 4, 12 Jiankang Rd, Shijiazhuang 050011, Hebei, Peoples R China
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通讯机构: [1]Hebei Med Univ, Dept Urol Surg, Hosp 4, 12 Jiankang Rd, Shijiazhuang 050011, Hebei, Peoples R China [*1]Department of Urology Surgery, The Fourth Hospital of Hebei Medical University, 12#, Jiankang Rd, 050011 Shijiazhuang, Hebei, People’s Republic of China
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