RESUMO
Apigenin, a naturally occurring flavonoid, is known to exhibit antitumor activity in many cancers. However, the regulatory mechanism of apigenin and the long noncoding RNAs (lncRNAs) altered upon apigenin treatment in oral squamous cell carcinoma (OSCC) remain unclear. In this study, we found that LINC00629 was significantly upregulated in response to apigenin treatment. Upregulated LINC00629 enhanced the growth-suppressive and proapoptotic effects of apigenin on OSCC cells by interacting with Mcl1 and facilitating its degradation. Subsequently, our data indicated that KLF10, an important transcription factor, directly bound to the promoter of LINC00629, facilitating its transcription and contributing to apigenin-induced LINC00629 expression. Collectively, these results suggest that the KLF10-LINC00629-Mcl1 axis plays an important role in the anticancer effects of apigenin.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/metabolismo , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Apigenina/farmacologia , Apigenina/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Linhagem Celular Tumoral , Neoplasias de Cabeça e Pescoço/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição de Resposta de Crescimento Precoce/genética , Fatores de Transcrição de Resposta de Crescimento Precoce/metabolismo , Fatores de Transcrição de Resposta de Crescimento Precoce/farmacologiaRESUMO
We examined the effect of transforming growth factor-b inducible early gene-1 (TIEG1) on the apoptosis of leukemic cell lines and expression of B-cell lymphoma 2 (Bcl-2) and phosphatase and tensin homolog (Pten). Four leukemic cell lines (HL-60, U937, Raji, and K562) were treated with 0, 1, 5, 10, and 20 ng/mL TIEG1, respectively. The cell growth inhibitory ratio was assessed using the MTT assay. An inhibitory curve was drawn, and half-maximal inhibitory concentration was calculated. Additionally, 1640 culture medium containing 10 ng/mL TIEG1 was used to culture leukemic cell lines for 0, 6, 12, 24, and 48 h. The apoptosis of each cell line at different time points was detected by flow cytometry. Total RNA was extracted before reverse transcription-polymerase chain reaction. The products of this reaction were analyzed by electrophoresis, and the expression of Bcl-2/Bcl-2-associated X protein (Bax) and Pten were detected. After treatment with TIEG1, proliferation of the 4 leukemic cell lines was inhibited both time- and dose-dependently. During apoptosis induction, the expression of Bcl-2 was decreased and the expressions of Bax and Pten were increased in the 4 leukemic cell lines induced by TIEG1 (P < 0.05). TIEG1 can inhibit the proliferation of leukemic cells and induce their apoptosis in a time- and dose-dependent manner. A close relationship exists between Bcl-2/Bax and Pten expression and cell apoptosis induced by TIEG1.
Assuntos
Apoptose , Fatores de Transcrição de Resposta de Crescimento Precoce/farmacologia , Fatores de Transcrição Kruppel-Like/farmacologia , PTEN Fosfo-Hidrolase/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proliferação de Células , Células HL-60 , Humanos , Células K562 , PTEN Fosfo-Hidrolase/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células U937 , Proteína X Associada a bcl-2/genéticaRESUMO
This study was aimed to investigate the influence of TIEG1 on apoptosis of HL-60 cells and the expression of Bcl-2/Bax. Different concentration of TIEG1 were used to treat HL-60 cells, the cell growth inhibition rate was detected by MTT method. After treating HL-60 cells with 12.03 ng/ml TIEG1, cell apoptosis was detected with flow cytometry. Bcl-2 and Bax was detected with RT-PCR. The results showed that TIEG1 had inhibitory effect on HL-60 cell proliferation, and in time-and dose-dependent manners. The more obvious inhibitory effect was observed in HL-60 cells treated with TIEG1 of 12.03 ng/ml. During the course of cell apoptosis, Bax expression increased, but Bcl-2 expression decreased (P < 0.05). It is concluded that TIEG1 inhibits HL-60 cell proliferation and induces apoptosis in time and dose-dependent manners. During the course of HL-60 cells apoptosis induced by TIEG1, Bcl-2/Bax are associated with HL-60 cell apoptosis induced by TIEG1.