RESUMO
BACKGROUND: Circular RNAs (circRNAs) play important roles in cancer progression and metastasis. However, the expression profiles and biological roles of circRNAs in non-small cell lung cancer (NSCLC) remain unclear. METHODS: In this study, we identified a novel circRNA, hsa_circ_0006834 (termed circ6834), in NSCLC by RNA-seq and investigated the biological role of circ6834 in NSCLC progression in vitro and in vivo. Finally, the molecular mechanism of circ6834 was revealed by tagged RNA affinity purification (TRAP), western blot, RNA immunoprecipitation, dual luciferase reporter gene assays and rescue experiments. RESULTS: Our results showed that circ6834 was downregulated in NSCLC tumor tissues and cell lines. Circ6834 overexpression inhibited NSCLC cell growth and metastasis both in vitro and in vivo, while circ6834 knockdown had the opposite effect. We found that TGF-ß treatment decreased circ6834 expression, which was associated with the QKI reduction in NSCLC cells and circ6834 antagonized TGF-ß-induced EMT and metastasis in NSCLC cells. Mechanistically, circ6834 bound to AHNAK protein, a key regulator of TGF-ß/Smad signaling, and inhibited its stability by enhancing TRIM25-mediated ubiquitination and degradation. In addition, circ6834 acted as a miRNA sponge for miR-873-5p and upregulated TXNIP gene expression, which together inactivated the TGF-ß/Smad signaling pathway in NSCLC cells. CONCLUSION: In conclusion, circ6834 is a tumor-suppressive circRNA that inhibits NSCLC progression by forming a negative regulatory feedback loop with the TGF-ß/Smad signaling pathway and represents a novel therapeutic target for NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Proteínas de Transporte , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , MicroRNAs , RNA Circular , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , RNA Circular/genética , MicroRNAs/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Animais , Camundongos , Linhagem Celular Tumoral , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Progressão da Doença , Movimento Celular/genética , Transdução de Sinais , Feminino , Fator de Crescimento Transformador beta/metabolismo , Masculino , Transição Epitelial-Mesenquimal/genéticaRESUMO
Objective: This study aims to investigate the potential of procalcitonin (PCT) levels and the C-reactive protein/procalcitonin (CRP/PCT) ratio as markers for distinguishing between infectious and neoplastic fever among febrile patients with malignant tumors. Methods: A retrospective analysis was conducted on febrile patients admitted to the hospital with malignant tumors. The patients were categorized into an infection group (67 cases) and a non-infection group (73 cases) based on the presence or absence of positive cultures. PCT levels, CRP levels, and CRP/PCT ratios were compared between the two groups. The receiver operating characteristic curve (ROC) was used to identify optimal cut-off values. Results: Data from 140 patients between January 2017 and December 2021 were extracted for analysis. Patients in the infected group showed elevated PCT levels and significantly decreased CRP/PCT ratios compared to the non-infected group (P < .01). The calculated cut-off values for distinguishing infectious and neoplastic fever were 0.52 ng/mL for PCT and 101.80 for CRP/PCT ratio. The ROC curve results revealed good sensitivity for both PCT (74.63%) and CRP/PCT (70.15%), while CRP/PCT demonstrated higher specificity (78.08%) compared to PCT (58.90%). Conclusions: PCT and CRP/PCT are both sensitive markers for identifying infection in patients with malignant tumors, with PCT showing slightly better sensitivity but lower specificity than CRP/PCT. Our findings suggest that CRP/PCT may be more valuable than PCT in distinguishing between infectious fever and neoplastic fever in cancer patients.
Assuntos
Neoplasias , Pró-Calcitonina , Humanos , Proteína C-Reativa/análise , Estudos Retrospectivos , Febre/diagnóstico , Neoplasias/complicações , Neoplasias/diagnóstico , BiomarcadoresRESUMO
Long non-coding RNAs (lncRNAs) have been suggested as important regulators of cancer development and progression in hepatocellular carcinoma (HCC). Nevertheless, the clinical value and biological roles of LINC00978 in HCC remain unclear. In this study, we detected the expression of LINC00978 in tumor tissues and serum of HCC patients, examined the roles of LINC00978 in HCC progression and elucidated the underlying molecular mechanisms. We found that LINC00978 expression was upregulated in tumor tissues and serum of HCC patients. Higher serum levels of LINC00978 could distinguish HCC patients from hepatitis and liver cirrhosis patients and healthy controls. LINC00978 knockdown inhibited HCC cell proliferation, migration and invasion while promoted cell cycle arrest and apoptosis. Overexpression of LINC00978 led to the opposite effects. LINC00978 knockdown also inhibited HCC growth and metastasis in mouse tumor models. Mechanistically, LINC00978 bound to EZH2 and mediated its accumulation at the promoter region of p21 and E-cadherin genes, leading to the trimethylation of H27K3 and the inhibition of p21 and E-cadherin expression. Moreover, the simultaneous depletion of p21 and E-cadherin expression reversed the inhibitory effects of LINC00978 knockdown on HCC cell proliferation, migration, and invasion. Taken together, these findings suggest that LINC00978 promotes HCC progression by inhibiting p21 and E-cadherin expression via EZH2-mediated epigenetic silencing. LINC00978 may represent a novel biomarker for HCC diagnosis, prognosis, and therapy.