RESUMO
Previous studies suggest that aberrant microRNA expression is common in plenty of cancers. The expression of miR-106a* was decreased in follicular lymphoma, but the expression and functions of miR-106a* in esophageal carcinoma (EC) remain unclear. In this study, we explored the expression and anti-oncogenic roles of miR-106a* in human EC. The expression of miR-106a* is significantly decreased in EC tissues and EC cell lines. Overexpression of miR-106a* suppressed EC cell proliferation, clonogenicity, G1/S transition, and induced apoptosis in vitro, but inhibition of miR-106a* facilitated cell proliferation, clonogenicity, G1/S transition. Luciferase reporter assay results showed that CDK2-associated Cullin 1 (CACUL1) was a direct target of miR-106a* in EC cells. Moreover, silencing CACUL1 resulted in the same biologic effects of miR-106a* overexpression in EC cells, which included suppressed EC cell proliferation, clonogenicity, and blocked G1/S transition through CDK2 pathway by inhibiting cell cycle regulators (Cyclin A, Cyclin E). Our data indicate that miR-106a* might play an anti-oncogenic role in EC by regulating CACUL1 expression, which suggest miR-106a* as a new potential diagnostic and therapeutic target for EC.
Assuntos
Proliferação de Células/genética , Proteínas Culina/genética , Neoplasias Esofágicas/genética , MicroRNAs/genética , Apoptose/genética , Linhagem Celular Tumoral , Proteínas Culina/biossíntese , Ciclina A/metabolismo , Ciclina E/metabolismo , Neoplasias Esofágicas/patologia , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/biossíntese , Interferência de RNA , RNA Interferente Pequeno/genética , Pontos de Checagem da Fase S do Ciclo Celular/genéticaRESUMO
MicroRNAs play critical roles in the development and progression of human cancers. Although miR—30a has been suggested to function as a tumor repressor in several tumors, its role in non—small cell lung cancer (NSCLC) has not been investigated in detail. This study investigated the expression and role of miR—30a in human NSCLC. The expression of miR—30a is significantly decreased in clinical NSCLC tissues and cell lines. Overexpression of miR—30a inhibited NSCLC cell proliferation, G1/S and S/G2 transition in vitro, whereas suppression of miR—30a facilitated NSCLC cell proliferation, G1/S and S/G2 transition. Using a luciferase reporter assay, insulin—like growth factor 1 receptor (IGF1R) was determined to be a direct target of miR—30a. Furthermore, silencing IGF1R resulted in the same biologic effects of miR—30a overexpression in NSCLC cells, which included suppressed NSCLC cell proliferation and trigering cell cycle arrest through PI3K/AKT signaling pathway by inhibiting cell cycle regulators (CDK2, CDK4, Cyclin A2 , Cyclin D1). These results demonstrate that miR—30a influences NSCLC progression through PI3K/AKT signaling pathway by targeting IGF1R in A549 cells, which suggest miR—30a as a novel strategy for NSCLC diagnosis and treatment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Somatomedina/genética , Apoptose , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Interferência de RNA , RNA Interferente Pequeno , Receptor IGF Tipo 1 , Pontos de Checagem da Fase S do Ciclo Celular/genética , Transdução de Sinais/genéticaRESUMO
Chemotherapy has been the first-choice treatment for small-cell esophageal cancer (SCEC), etoposide plus cisplatin or carboplatin (EP/CP) is the most commonly recommended chemotherapeutical strategy. However, the choice of chemotherapy in treating SCEC has not been validated by studies of large cohorts of cases because of the rarity of the malignancy, and the efficacy superiority of EP/CP over other chemotherapy combinations has not been confirmed. The present case series analysis was conducted to address the above issues. Reported studies of SCEC patients were retrieved. Case series with more than five patients were enrolled. Eight patients treated in our institute were also included as another case series. Data pertaining to clinical stages, treatment regimens, and survival time were collected and analyzed. Altogether, 19 SCEC case series were enrolled, including 164 male and 61 female patients with a median age of 63.5 years. The follow-up time ranged from 0.1 to 221 months (median 12.3 months). The median survival time (MST) was 19 months for limited disease (LD) patients (124 cases) and 9 months for extensive disease (ED) patients (88 cases) (P<0.001). For LD patients, MST was obviously prolonged by chemotherapeutical regimens (20 vs. 10 months, P<0.01), whereas this superiority was not proved in ED patients (10 vs. 10 months, P>0.05). EP/CP did not result in significantly longer MST, compared with that of the cases treated by other chemotherapy combinations (P>0.05, for either LD or ED cases). Chemotherapy prolongs the survival time of the LD SCEC patients, which indicates that chemotherapeutical treatment is effective for SCEC. EP/CP, as commonly recommended multidrug chemotherapy regimen, is not superior to other chemotherapy combinations.