Browsing by Subject "LUAD"

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    Anesthetic propofol suppresses growth and metastasis of lung adenocarcinoma in vitro through downregulating circ-MEMO1-miR-485-3p-NEK4 ceRNA axis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Chen, Lei; Wu, Guangyi; Li, Yongle; Cai, Qiaoying
    Background. Recently, circular RNAs (circRNAs) have been emerging as new regulators in the propofol-induced tumor-suppressive role. Here, we intended to investigate the involvement of circRNAMediator of cell motility 1 (circ-MEMO1; hsa_circ_0007385) in propofol role in cancer hallmarks of lung adenocarcinoma (LUAD). Methods. Real-time quantitative PCR and western blotting examined transcriptional and translational levels of circ-MEMO1, microRNA (miR)-485-3p, and NIMArelated kinase-4 (NEK4), and markers of growth and metastasis including E-cadherin, CyclinD1, and Vimentin. Cancer hallmarks were measured by 3-(4, 5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, 5-ethynyl-2-deoxyuridine assay, and transwell assay. The interaction among circMEMO1, miR-485-3p, NEK4 was determined by dualluciferase reporter assay and Pearson’s correlation analysis. Results. Circ-MEMO1 and NEK4 were highexpressed, and miR-485-3p was low-expressed in LUAD patients and cells; moreover, circ-MEMO1 and NEK4 expression in LUAD cells could be suppressed, whereas miR-485-3p could be elevated with propofol anesthesia. Functionally, propofol restrained cell viability, cell cycle entrance, cell proliferation, migration, and invasion of LUAD cells, accompanied by promoted E-cadherin and depressed CyclinD1 and Vimentin. Coincidently, high circ-MEMO1 was associated with low overall survival of LUAD patients, and overexpressing circ-MEMO1 could overall attenuate propofol effects in LUAD cells. Of note, upregulating miR-485-3p and/or interfering NEK4 could partially countermand the adverse impacts of circ-MEMO1 on propofol’s role in LUAD cells. Importantly, circMEMO1 acted as a sponge for miR-485-3p to modulate the expression of miR-485-3p-targeted oncogene NEK4. Conclusion. Promoting the circ-MEMO1-miR-485- 3p-NEK4 axis might halt the tumor-inhibiting role of propofol in LUAD cells in vitro, suggesting a potential epigenetic pathway of propofol.
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    Depleting hsa_circ_0000567 suppresses acquired gefitinib resistance and proliferation of lung adenocarcinoma cells through regulating the miR-377-3p / ZFX axis: an in vitro and in vivo study
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Wang, Lanjun; Li, Mengqi; Lian, Rong
    Background. Circular RNAs (circRNAs) expression profile has been reported in lung adenocarcinoma (LUAD) cells resistant to gefitinib, and hsa_circ_0000567 was abnormally upregulated. However, its precise role in gefitinib resistance remains unclarified. Methods. Levels of hsa_circ_0000567, microRNA (miR)-377-3p and zinc finger protein X-linked (ZFX) were detected by real-time quantitative PCR. Direct attachment was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Gefitinib resistance was measured by MTT assay, colony formation assay, flow cytometry, western blotting, and xenograft in mice. Results. Expression of hsa_circ_0000567 was upreguated in human gefitinib-resistant human LUAD tissues and cells (HCC827/GR and PC9/GR). Clinically, higher hsa_circ_0000567 correlated with advanced tumor burden. Blockage of hsa_circ_0000567 suppressed cell viability, half maximal inhibitory concentration (IC50) value, colony formation ability, and expression of Bcl-2 and proliferating cell nuclear antigen (PCNA) in HCC827/GR and PC9/GR cells under gefitinib treatment or not, accompanied with enhanced apoptosis rate and Bax expression. In vivo, tumor growth of PC9/GR cells untreated and treated with gefitinib was restrained by silencing hsa_circ_0000567. miR-377-3p was directly regulated by hsa_circ_0000567, and then targeted ZFX. Similar to hsa_circ_0000567 knockdown, overexpressing miR377-3p inhibited chemoresistance in genitinib-resistant LUAD cells in vitro, whereas, depleting miR-377-3p was able to promote gefitinib resistance in spite of hsa_circ_0000567 knockdown. Moreover, restoring ZFX abrogated miR-377-3p-mediated chemosensitivity in genitinib-resistant LUAD cells in vitro. Conclusion. The hsa_circ_0000567/miR-377- 3p/ZFX axis might contribute to acquired gefitinib resistance in LUAD cells both in vitro and in vivo, suggesting hsa_circ_0000567 as a novel therapeutic target in treatment of gefitinib-resistant LUAD.