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Introduction: Lung cancer is the malignant tumor with the fastest increase in morbidity and mortality and the greatest threat to human health and life. Long non-coding RNA (lncRNA) is emerging as an important regulator in many cancers. Recently, it was found that lncRNA prostate cancer associated transcript 1 (PCAT-1) was up-regulated in lung cancer, playing oncogenic roles. However, the underlying regulatory mechanism of PCAT-1 remains unknown.Material and Methods: The expression levels of PCAT-1 and miR-324-5p were analyzed by real-time PCR, and RAP1A expression was determined by western blotting. RNA pull-down, luciferase and western blotting assays were used to examine the target relationship between PCAT-1 and miR-324-5p or that between miR-324-5p and RAP1A. The functional effects of PCAT-1 and miR-324-5p were examined using cell viability and cell apoptosis assays.Results: PCAT-1 overexpression remarkably promoted cell proliferation and suppressed cell apoptosis. Mechanistic investigations demonstrated that PCAT-1 can interact with miR-324-5p and repress its expression, thereby increasing the expression of its target RAP1A. Additionally, rescue experiments revealed that PCAT-1 served as an oncogene partly through sponging miR-324-5p and upregulating RAP1A in lung cancer cells.Conclusions: Our findings demonstrate that on account of the dual function of pro-proliferation and anti-apoptosis, PCAT-1/miR-324-5p/RAP1A may be novel candidates for application in the diagnosis, prognosis and therapy of lung cancer. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. This study aims to understand the underlying mechanism of lncRNA, actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1) in mediating chemotherapeutic resistance in NSCLC. The levels of AFAP1-AS1 in NSCLC tissues and cells were determined using RT-PCR. The protein levels of RRM2, EGFR, and p-AKT were analyzed using Western blotting. Binding between AFAP1-AS1 and miR-139-5p was confirmed using dual luciferase reporter and RNA immunoprecipitation (RIP) assays, and binding between miR-139-5p and RRM2 was confirmed by a dual luciferase reporter assay. NSCLC cell proliferation, apoptosis, and colony formation were examined using MTT, flow cytometry, and colony formation assays, respectively. It was found that AFAP1-AS1 expression was upregulated in NSCLC tissues and cells. In addition, AFAP1-AS1 bound to and downregulated the expression of miR-139-5p, which was reduced in NSCLC tissues. Knockdown of AFAP1-AS1 and overexpression of miR-139-5p inhibited NSCLC cell proliferation, colony formation and chemotherapy resistance and increased cell apoptosis. Additionally, AFAP1-AS1 upregulates RRM2 expression via sponging miR-139-5p. Furthermore, AFAP1-AS1 enhanced NSCLC cell proliferation and chemotherapy resistance through upregulation of RRM2 by inhibiting miR-139-5p expression. Moreover, RRM2 promoted cellular chemotherapy resistance by activating EGFR/AKT. Finally, knockdown of AFAP1-AS1 significantly suppressed tumor growth and chemoresistance in nude mice. In conclusion, AFAP1-AS1 promoted chemotherapy resistance by supressing miR-139-5p expression and promoting RRM2/EGFR/AKT signaling pathway in NSCLC cells. [ABSTRACT FROM AUTHOR]