RESUMO
[This corrects the article DOI: 10.7150/ijbs.59430.].
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Mucin 3A (MUC3A) is highly expressed in non-small cell lung cancer (NSCLC), but its functions and effects on clinical outcomes are not well understood. Tissue microarray of 92 NSCLC samples indicated that high levels of MUC3A were associated with poor prognosis, advanced staging, and low differentiation. MUC3A knockdown significantly suppressed NSCLC cell proliferation and induced G1/S accumulation via downregulating cell cycle checkpoints. MUC3A knockdown also inhibited tumor growth in vivo and had synergistic effects with radiation. MUC3A knockdown increased radiation-induced DNA double strain breaks and γ-H2AX phosphorylation in NSCLC cells. MUC3A downregulation inhibited the BRCA-1/RAD51 pathway and nucleus translocation of P53 and XCRR6, suggesting that MUC3A promoted DNA damage repair and attenuated radiation sensitivity. MUC3A knockdown also resulted in less nucleus translocation of RELA and P53 in vivo. Immunoprecipitation revealed that MUC3A interacted with RELA and activated the NFκB pathway via promoting RELA phosphorylation and interfering the binding of RELA to IκB. Our studies indicated that MUC3A was a potential oncogene and associated with unfavorable clinical outcomes. NSCLC patients with a high MUC3A level, who should be more frequent follow-up and might benefit less from radiotherapy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Mucina-3/genética , Tolerância a Radiação/genética , Animais , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Reparo do DNA/genética , Reparo do DNA/efeitos da radiação , Feminino , Humanos , Proteínas I-kappa B/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Nucleares , Fosforilação , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação , Fator de Transcrição RelA/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Hepatitis B X-interacting protein (HBXIP) is highly expressed in many cancers, but the correlation between the expression of HBXIP and the clinical significance and underlying molecular mechanisms in colorectal cancer (CRC) is still unclear. We selected 186 specimens from CRC patients for analyzing the relationship between the expression of HBXIP and the clinical-pathological features by immunohistochemistry. Migration and invasion experiments were performed to examine the effect of HBXIP on CRC cell metastasis. Besides, we also explored the possible molecular mechanism of HBXIP regulation of CRC cell metastasis by Western blot. Our data indicated that the HBXIP was overexpressed in CRC tissues. High HBXIP expression was correlated with metastasis and shorter survival times in patients with CRC and served as an independent factor for poor prognosis. Moreover, HBXIP promotes CRC metastasis by enhancing the epithelial-mesenchymal transition (EMT) process. Our findings provide the first evidence that HBXIP induces EMT to promote metastasis and predicts the poor prognosis of CRC. Therefore, HBXIP may become a new target for CRC treatment.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Colorretais/diagnóstico , Transição Epitelial-Mesenquimal , Proteínas Adaptadoras de Transdução de Sinal/análise , Idoso , Biomarcadores Tumorais , Western Blotting , Linhagem Celular Tumoral , Neoplasias Colorretais/química , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Células HCT116 , Humanos , Masculino , Invasividade Neoplásica , Prognóstico , Análise de SobrevidaRESUMO
FePt-Cys nanoparticles (FePt-Cys NPs) have been well used in many fields, despite their poor solubility and stability. We synthetized a cysteine surface modified FePt NPs, which exhibited good solubility, stability and biocompatibility. We explored the insight mechanisms of the antitumor effects of this new nanoparticle system in lung cancer cells. In the in vitro study, FePt-Cys NPs induced a reactive oxygen species (ROS) burst, which suppressed the antioxidant protein expression and induced cell apoptosis. Furthermore, FePt-Cys NPs prevented the migration and invasion of H1975 and A549â¯cells. These changes were correlated with a dramatic decrease in MMP-2/9 expression and enhanced the cellular attachment. We demonstrated that FePt-Cys NPs promoted the effects of chemo-radiation through activation of the caspase system and impairment of DNA damage repair. In the in vivo study, no severe allergies or drug-related deaths were observed and FePt-Cys NPs showed a synergistic effect with cisplatin and radiation. In conclusion, with good safety and efficacy, FePt-Cys NPs could therefore be potential sensitizers for chemoradiotherapy.