RESUMO
BACKGROUND: Breast cancer (BRCA) is one of the most common cancers in women and is the leading cause of cancer-related deaths in women. TNFSF12, originally a member of the TNF superfamily, is considered a key molecule that is associated with poor prognosis of many cancers. However, its role in progression of BRCA remains unclear. METHODS: In this study, the expression profile and clinical information of TNFSF12 across various cancers were obtained from The Cancer Genome Atlas (TCGA) database. Differences in TNFSF12 expression levels between carcinoma and paraneoplastic cancers were compared, and its association with prognosis was examined. Functional enrichment analysis was conducted to explore the potential signaling pathways and biological functions linked with TNFSF12. Moreover, the correlation between TNFSF12 and immune cell infiltration, response to immune checkpoint inhibitors (ICIs), and response to chemotherapy were evaluated. TNFSF12 level in BRCA and normal serum was detected by ELISA. RESULTS: TNFSF12 was lowly expressed in BRCA and is significantly associated with PAM50. TNFSF12 low expression correlates with poor overall survival, particularly among HER2-positive patients. Patients with high level of TNFSF12 expression are usually accompanied with elevated levels of various immune cells, including CD8 T cells, cytotoxic cells, DCs, eosinophils, iDCs, mast cells, neutrophils, NK CD56bright cells, NK cells, pDC, T cells, Tem, and TFH Th17 cells, and exhibit sensitivity to immune checkpoint inhibitors. Functional enrichment analysis indicates significant activation of KRAS signaling, TNFA signaling via NFKB, and epithelial-mesenchymal transition (EMT) in the high TNFSF12 expression group, while MTORC1 signaling, MYC, G2M checkpoint, and E2F targets are inhibited. Furthermore, patients in the low expression group demonstrate higher sensitivity to paclitaxel and rapamycin, whereas those in the high expression group show increased sensitivity to erlotinib and foretinib. ELISA analysis also confirmed a significant decrease of TNFSF12 protein levels in BRCA patients. CONCLUSION: This study presents a comprehensive analysis of the close correlation between TNFSF12 and prognosis, immune response, as well as the effectiveness of chemotherapeutic agents in BRCA patients.
RESUMO
Recently, increasing evidence showed that circular RNAs (circRNAs) play critical roles in tumor progression. However, the roles of hsa_circ_0062389 in non-small cell lung cancer (NSCLC) development remain unclear. In the present study, hsa_circ_0062389 expression was significantly increased in NSCLC tissues and cell lines. High hsa_circ_0062389 expression was associated with advanced TNM stage and lymph-node metastasis. Function assays showed that hsa_circ_0062389 suppression reduced NSCLC cells proliferation and arrested cell cycle in G0/G1 phase. In mechanism, hsa_circ_0062389 directly interacted with miR-103a-3p in NSCLC, and CCNE1 acted as a target of miR-103a-3p. Furthermore, rescue assays showed that miR-103a-3p suppression or CCNE1 overexpression abolished the effects of hsa_circ_0062389 suppression on lung cancer cells progression. Therefore, our results showed that the hsa_circ_0062389/miR-103a-3p/CCNE1 axis might contribute to the tumorigenesis of NSCLC, which provided a new strategy for cancer treatment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Ciclina E/genética , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , Proteínas Oncogênicas/genética , RNA Circular/metabolismo , Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia , RNA Circular/genética , RNA Interferente Pequeno/metabolismo , Regulação para CimaRESUMO
Recent studies showed that long non-coding RNAs (lncRNAs) could play critical roles in tumors progression. However, the performance of LINC01354 is still limited in non-small cell lung cancer (NSCLC). In the current study, our results showed that LINC01354 was significantly increased in NSCLC tissues and cell lines. High LINC01354 expression was associated with advanced TNM stage and poor prognosis in NSCLC patients. Loss-of-function assays revealed that knockdown of LINC01354 reduced lung cancer cells proliferation and invasive ability in vitro. Subsequently, mechanism studies showed that LINC01354 positively regulated the ATF1 expression via competitive binding to miR-340-5p. Therefore, our results illustrated that LINC01354 might act as an oncogenic role by modulating the miR-340-5p/ATF1 axis, providing a novel therapeutic therapy for NSCLC treatment.