RESUMO
The aim of this study was to determine oncogenic and tumor-suppressing miRNA profiles associated with the development and progression of cancer using tumor tissues from patients with colorectal cancer (stage II) that did not show nodal spread or advanced metastasis to identify potential biomarkers. A microarray system (GeneChip miRNA 4.0 Array chip, Affymetrix) was used to determine the microRNA profiles of five patients with stage II colon cancer based on normal and colon tumor tissues. Of 32 identified miRNAs, an increase in three microRNAs (hsa-miR-4745-5p, hsa-miR-6126, and hsa-miR-1469) was observed in tumor tissues relative to that in control tissues. Additionally, this study demonstrated for the first time that the expression of the 8 miRNAs (hsa-miR-378i, hsa-miR-378a-3p, hsa-miR-378c, hsa-miR-378d, hsa-miR-378e, hsa-miR-378f, hsa-miR-378a-5p, and hsa-miR-378g) from miR-378 members among the differentially expressed miRNAs is reduced. The target genes of these downregulated miRNAs were determined by using DIANA miRPath v3. The effect of identified genes on colon cancer stage II was determined the biological process and biological pathway using Funrich Gene Enrichment. It was revealed that these miRNAs were affected the signaling pathways which control cell proliferation, cell-cell interaction, and apoptosis in stage II colon cancer. In patients with early stage II colon cancer, miR-378 can be used as a biomarker of colorectal cancer. Thus, miR-378 can facilitate treatment with early diagnosis.
Assuntos
Neoplasias do Colo/diagnóstico , Neoplasias do Colo/genética , MicroRNAs/genética , Adulto , Biomarcadores Tumorais/genética , Carcinogênese/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Biologia Computacional , Progressão da Doença , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de SinaisRESUMO
In this study, we investigated the potential effects of naringenin on the motility of MAT-LyLu cells, which overexpress voltage-gated sodium channels and whose metastatic behaviours are associated with these channels. We first determined the concentration of naringenin that did not show toxic effects or block cell growth. Then, the effects of naringenin on cell motility in the lateral and vertical directions were tested by wound healing assays and transwell invasion assays, respectively. Finally, to determine the suppressive effects of naringenin on cell movement in both directions, the expression of the SCN9A gene, which encodes Nav1.7 voltage-gated sodium channel, was determined by real-time quantitative polymerase chain reaction. The data revealed that high concentrations of naringenin (75⯵M) inhibited cell proliferation, whereas low concentrations (5 and 10⯵M) decreased the movement of MAT-LyLu cells. Moreover, 10⯵M naringenin displayed inhibitory effects on cell movement by reducing the expression of the SCN9A gene at the mRNA level. In conclusion, naringenin was found to have direct or indirect blocking activity on voltage-gated sodium channels encoded by the SCN9A gene.
Assuntos
Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Flavanonas/farmacologia , Canal de Sódio Disparado por Voltagem NAV1.7/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica , Humanos , Cinética , Masculino , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Hedera helix L., a member of Araliaceae family, has antiproliferative, cytotoxic, antimicrobial, antifungal, antiprotozoal and anti-inflammatory effects, and is used in cosmetics. The aim of the present study was to investigate the effect of treatment with extracts of leaves and unripened fruits of H. helix on rat prostate cancer cell lines with markedly different metastatic potentials: Mat-LyLu cells (strongly metastatic) and AT-2 cells (weakly metastatic). The effects of the extracts on cell kinetics and migration were determined. Tetrodotoxin was used to block the voltage-gated sodium channels (VGSCs) associated specifically with Mat-LyLu cells. Cell proliferation was detected spectrophotometrically using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. The mitotic index was determined using the Feulgen staining method. Lateral motility was quantified by wound-healing assays. The results of the present study demonstrated that cell kinetics (proliferation and mitotic activity) and motility were inhibited by ethanolic leaf extract of H. helix. The ethanolic extract of H. helix fruit suppressed Mat-LyLu cell migration, with no effect on proliferation. The opposite effects were observed in AT-2 cells; migration was not affected but proliferation was inhibited. In conclusion, the ethanolic fruit extract of H. helix may inhibit the cell migration of Mat-LyLu cells by blocking VGSCs. However, the effect of ethanolic leaf extract of H. helix treatment on the lateral motility of the cancer cells is unclear.
