RESUMO
IL-11 exerts important functions involved in tumorigenesis and cancer progression. However, the underlying functional role of IL-11 in esophageal squamous cell cancer (ESCC) is not well known. In this paper, we demonstrated that IL-11 expression was increased in esophageal cancer compared with normal tissues, whereas knockdown of IL-11 could inhibit the proliferation and invasion of Eca109 and KYSE410 ESCC cells. Besides, we found that the stability and expression of IL-11 was regulated by lnc-ATB in Eca109 and KYSE410 ESCC cells. More importantly, we found that knockdown of IL-11 partly abolished lnc-ATB-mediated the proliferation and invasion of Eca109 and KYSE410 ESCC cells. Collectively, these results indicated that IL-11 mediated by lnc-ATB increased the proliferation and invasion of ESCC cells, which may provide a promising therapeutic option for suppressing ESCC progression.
Assuntos
Carcinoma de Células Escamosas/genética , Proliferação de Células/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Interleucina-11/genética , Invasividade Neoplásica/genética , RNA Longo não Codificante/genética , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Invasividade Neoplásica/patologiaRESUMO
Increasing evidence shows that aberrant epigenetic regulation of tumor suppressor genes is a contributing factor to their altered expression in esophageal squamous cell carcinoma (ESCC). In the current study, we investigate the role of DOK7 in ESCC cells. We found that enforced expression of DOK7 inhibited the proliferation and invasion of ESCC cells. We also found that treatment of ESCC cells with the DNA methylation inhibitor, 5-aza-2-deoxycytidine (5-azadC), induced the demethylation of DOK7 in promoter and DOK7 expression. Moreover, silencing DNMT3A decreased methylation of DOK7 and increased DOK7 expression, followed by repressing the proliferation and invasion of ESCC cells. Collectively, our data indicated that silencing DNMT3A inhibits proliferation and invasion in ESCC cells by inducing demethylation of DOK7.
Assuntos
Proliferação de Células/genética , DNA (Citosina-5-)-Metiltransferases/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteínas Musculares/genética , Invasividade Neoplásica/genética , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/genética , DNA Metiltransferase 3A , Decitabina , Epigênese Genética/efeitos dos fármacos , Epigênese Genética/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Inativação Gênica/fisiologia , Humanos , Regiões Promotoras Genéticas/efeitos dos fármacos , Regiões Promotoras Genéticas/genéticaRESUMO
Resistance to chemotherapy is a major obstacle for the effective treatment of cancers. The mechanism of chemo-resistance is still poorly understood, however, mounting evidence supports a role for microRNAs (miRNAs) in modulating key cellular pathways mediating response to chemotherapy. microRNA-21 (miR-21) has been implicated in many cancers and contributed to chemo-resistance, but its role in gastric cancer drug resistance still remains unexplored. The aim of this study was to investigate whether miR-21 mediated resistance of the gastric cancer cell line SGC7901 to the chemotherapeutic agent cisplatin (DDP). Our study found that the expression of miR-21 upregulated in the cisplatin resistant cell line SGC7901/DDP compared to its parental line SGC7901. Moreover, over-expression of miR-21 significantly decreased antiproliferative effects and apoptosis induced by cisplatin, while knockdown of miR-21 dramatically increased antiproliferative effects and apoptosis induction by cisplatin. In addition, miR-21 induced cell survival and cisplatin resistance through downregulating the expression of phosphatase and tension homolog deleted on chromosome 10 (PTEN) and activation of Akt pathway. Inhibition of Akt using PI3K inhibitor LY 294002 could abrogate miR-21 induced cell survival. These results suggest that miR-21 may provide a novel mechanism for understanding cisplatin resistance in gastric cancer by modulating PTEN/PI3K/Akt pathway.
