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LncRNA LOXL1‐AS1/miR‐let‐7a‐5p/EGFR‐related pathway regulates the doxorubicin resistance of prostate cancer DU‐145 cells

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Our study aimed to investigate the effects of lncRNA LOXL1‐AS1/miR‐let‐7a‐5p/EGFR‐axis on prostate cancer (PCa) progression. Microarray analysis was conducted to determine differentially expressed lncRNAs and mRNAs. Gene Set Enrichment analysis… Click to show full abstract

Our study aimed to investigate the effects of lncRNA LOXL1‐AS1/miR‐let‐7a‐5p/EGFR‐axis on prostate cancer (PCa) progression. Microarray analysis was conducted to determine differentially expressed lncRNAs and mRNAs. Gene Set Enrichment analysis was implemented for verification of dys‐regulated signaling pathways between DU‐145 cells and doxorubicin‐resistant prostate cancer DU‐145 cells. Relative expression of lncRNA LOXL1‐AS1 in doxorubicin‐resistant prostate cancer DU‐145 cells was analyzed by qRT‐PCR. CCK‐8 assay and flow cytometry analysis were employed to detect cell proliferation and apoptosis, respectively. Cell migration was performed by transwell assay. Furthermore, targeted relationships between lncRNA LOXL1‐AS1 and miR‐let‐7a‐5p, as well as miR‐let‐7a‐5p and EGFR were predicted using bioinformatics analysis and validated by dual‐luciferase reporter gene assay. Besides, tumor xenograft assay was utilized for verification of the roles of LOXL1‐AS1 in PCa progression in vivo. Microarray analysis showed that lncRNA LOXL1‐AS1 and EGFR were both downregulated, while miR‐let‐7a‐5p was upregulated in doxorubicin‐resistant prostate cancer DU‐145 cells. MiR‐let‐7a‐5p could target both lncRNA LOXL1‐AS1 and EGFR to affect PCa progression. Upregulation of lncRNA LOXL1‐AS1 promoted cell proliferation and migration, while suppressed cell apoptosis. Besides, it was further confirmed that EGFR was downregulated in drug‐resistant PCa cells and negatively correlated with miR‐let‐7a‐5p. Tumor xenograft assay verified that silence of lncRNA LOXL1‐AS1 inhibited the tumor growth in vivo in DU‐145 cells. Our results demonstrated that the lncRNALOXL1‐AS1/miR‐let‐7a‐5p/EGFR axis significantly affected proliferation, migration, and apoptosis of drug‐resistant DU‐145 Cells, which may provide us with a potential treatment strategy for drug‐resistant PCa patients. © 2019 IUBMB Life, 2019

Keywords: mir let; as1; loxl1 as1; prostate cancer; 145 cells; lncrna loxl1

Journal Title: IUBMB Life
Year Published: 2019

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