RESUMO
OBJECTIVE: The present study aimed to determine the expression of long non-coding RNA (lncRNA) FOXD3 antisense RNA 1 (FOXD3-AS1) in lung cancer tissues and to explore its underlying mechanisms in mediating non-small cell lung cancer (NSCLC) progression. MATERIALS AND METHODS: Gene expression levels were determined by quantitative real-time PCR; lung cancer cell proliferation and invasion were determined by in vitro functional assays; protein levels were determined by Western blot assay; xenograft nude mice model was used to evaluate the in vivo tumor growth of lung cancer cells; Luciferase reporter assay determined the interactions among FOXD3-AS1, miR-127-3p, and mediator complex subunit 28 (MED28). RESULTS: Data mining and analysis of the clinical sample showed that FOXD3-AS1 expression was significantly up-regulated in lung cancer tissues. In vitro functional assays demonstrated that FOXD3-AS1 overexpression promoted NSCLC cell proliferation and invasion, while FOXD3-AS1 knockdown exerted tumor-suppressive effects on NSCLC cells. Moreover, FOXD3-AS1 interacted with miR-127-3p by acting as a competing endogenous RNA to suppress miR-127-3p expression, while miR-127-3p repressed MED28 expression by targeting MED28 3' untranslated region in NSCLC cells. Mechanistically, the oncogenic effects of FOXD3-AS1 overexpression were significantly attenuated by miR-127-3p overexpression and MED28 knockdown in NSCLC cells. In the xenograft mice model, FOXD3-AS1 knockdown suppressed in vivo tumor growth of A549 cells, and also up-regulated miR-127-3p expression and repressed MED28 expression in the xenograft tumors. In the clinical aspect, the downregulation of miR-127-3p and up-regulation of MED28 were respectively detected in lung cancer tissues. CONCLUSIONS: Our findings provided new evidence that the FOXD3-AS1 regulated NSCLC progression via targeting the miR-127-3p/MED28 axis.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Pulmonares/metabolismo , Complexo Mediador/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Células Cultivadas , Fatores de Transcrição Forkhead/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Complexo Mediador/genética , MicroRNAs/genética , RNA Longo não Codificante/genéticaRESUMO
The petrol ether, ethyl acetate and methanol extracts of eight medicinal polypore fungi from China were evaluated for cytotoxic activities using MTT-dye assay. All the petrol ether and ethyl acetate extracts exhibited cytotoxicity against human cervix epitheloid carcinoma cell lines (Hela) and human hepatoma cell lines (SMMC-7721). Cytotoxicity activity was also observed in the methanol extracts of Phellinus conchatus and Pycnoporus sanquineus, but the methanol extracts from Cryptoporus volvatus, Fomitopsis pinicola, Fomes hornodermus, Lenzites betulina, Trametes gibbosa and Trametes orientalis showed weak activity when compared with quercetin.
Assuntos
Antibióticos Antineoplásicos/análise , Polyporaceae/química , Linhagem Celular Tumoral , Humanos , Medicina Tradicional ChinesaRESUMO
The synthetic progestin cyproterone acetate (CPA) has been recently shown to elicit DNA repair synthesis in cultured rat hepatocytes and to form adducts with rat hepatocyte DNA in vitro and in vivo. In the present study we have examined the genotoxic potential of the structural analogues of CPA, chlormadinone acetate (CMA) and megestrol acetate (MGA) in rat liver cells. CPA strongly induced DNA repair synthesis in hepatocyte cultures from females but not from males. In contrast, CMA and MGA (2-50 microM) did not detectably increase repair synthesis in cultured hepatocytes from either gender. CMA and MGA, however, caused the formation of DNA adducts detectable by the 32P-postlabelling technique. At a concentration of 30 microM, between 30 and 50 adducts/10(9) nucleotides were found with MGA and CMA in cultured hepatocytes of female rats, and between 5 and 20 adducts/10(9) nucleotides were found in hepatocytes of males. By comparison, 30 microM CPA has been found to produce 1670 adducts/10(9) nucleotides in hepatocytes from female rats. CMA and MGA also induced low levels of DNA adducts in vivo. When female rats were treated with 100 mg/kg of CMA or MGA per os, the adduct levels were 2 and 19 adducts/10(9) nucleotides respectively. The results indicate that both CMA and MGA show some genotoxicity in rat liver cells, which is, however, much lower than that for CPA. Our findings further suggest that the high genotoxicity of CPA is associated with the presence of the 1,2 alpha-methylene group, which is absent in CMA and MGA.
