Circ0060467 sponges miR-6805 to promote hepatocellular carcinoma progression through regulating AIFM2 and GPX4 expression.

BACKGROUND: Circular RNAs (circRNAs) represent a subset of non-coding RNAs implicated in the regulation of diverse biological processes, including tumorigenesis. However, the expression and functional implications of circ0060467 in hepatocellular carcinoma (HCC) remain elusive. In this study, we aimed to elucidate the role of circ0060467 in modulating the progression of HCC. METHODS: Differentially expressed circRNAs in HCC tissues were identified through circRNA microarray assays. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays revealed the upregulation of circ0060467 in both HCC cell lines and tissues. Various assays were conducted to investigate the roles of circ0060467 in HCC progression. Additionally, RNA immunoprecipitation (RIP) assays and luciferase assays were carried out to assess the interactions between circ0060467, microRNA-6085 (miR-6085), apoptosis-inducing factor mitochondria-associated 2 (AIFM2), and glutathione peroxidase 4 (GPX4) in HCC. RESULTS: Microarray and qRT-PCR analyses demonstrated a marked elevation of circ0060467 in HCC tissues and cell lines. Knockdown of circ0060467 suppressed HCC cell proliferation. Luciferase reporter and RIP assays confirmed the binding of circ0060467, AIFM2, and GPX4 to miR-6805. Subsequent experiments revealed that circ0060467 competes with AIFM2 and GPX4, thereby inhibiting cancer cell ferroptosis by binding to miR-6085 and promoting hepatocellular carcinoma progression. CONCLUSIONS: Collectively, circ0060467 modulates the levels of AIFM2 and GPX4, crucial regulators of tumor cell ferroptosis, by acting as a sponge for miR-6085 in HCC. Thus, circ0060467 may represent a novel diagnostic marker and therapeutic target for HCC.

Molecular mechanism of Rhubarb in the treatment of non-small cell lung cancer based on network pharmacology and molecular docking technology.

Non-small cell lung cancer (NSCLC) is one of the leading causes of death in the world. Rhubarb, a traditional Chinese medicine, has been widely used in the treatment of inflammatory and autoimmune diseases. This study aimed to investigate the possible mechanism of the rhubarb herb in the treatment of NSCLC by means of network pharmacology and molecular docking and to provide a theoretical basis for experiments and clinical application of traditional Chinese medicine for treating lung cancer. The main active chemical components and targets of rhubarb were screened through Swiss Target Prediction, TargetNet, and Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The protein-protein interaction (PPI) network was built via an in-depth exploration of the relationships between the proteins. The enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to predict the potential roles in the pathogenesis of NSCLC via the R package cluster Profiler. Potential targets and active ingredients associated with anti-tumor effects of rhubarb were screened by reverse molecular docking. By searching databases and literature, a total of 295 targets were found for the 21 active ingredients in rhubarb. There were 68 common target genes associated with NSCLC, of which 9 are derived from FDA-approved drugs. GO Gene Set Enrichment Analysis (GSEA) explored up to 1103 biological processes, 62 molecular functions, and 18 cellular components. KEGG GSEA explored 65 basic pathways, and 71 disease pathways. Four key targets (JUN, EGFR, BCL2, and JAK2) were screened through the protein-protein interaction network, target-pathway network, and FDA drug-target network. Molecular docking results showed that these key targets had relatively strong binding activities with rhubarb's active ingredients. The present study explored the potential pharmacological mechanisms of rhubarb on NSCLC, promoting the clinical application of rhubarb in treating NSCLC, and providing references for advanced research.

Gemcitabine Combined with Cisplatin Has a Better Effect in the Treatment of Recurrent/Metastatic Advanced Nasopharyngeal Carcinoma.

Objective: To explore the efficacy and safety of gemcitabine (GEM) combined with cisplatin (DDP) in the treatment of recurrent/metastatic nasopharyngeal carcinoma (NPC). Methods: A total of 100 patients with recurrent/metastatic NPC treated in the First Affiliated Hospital, Hengyang Medical School, University of South China from January 2018 to March 2020 were retrospectively enrolled. Based on different chemotherapy schemes, they were assigned to an observation (Obs) group (DDP + GEM, n = 55) and a control (Con) group [DDP + FU (fluorouracil), n = 45]. The two groups were compared regarding the following items: therapeutic efficacy; serum levels of platelet-derived growth factor-BB (PDGF-BB), soluble epithelial cadherin (SE-CAD), and inflammation-related factors before and after treatment; toxic and side effects; 1-year survival rate; and quality of life (QOL) 6 months after treatment. Results: The Obs group outperformed the Con group in therapeutic efficacy (P < 0.05). There were no significant differences in the levels of PDGF-BB, SE-CAD, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α between the two groups before treatment (P > 0.05). After treatment, better improvements in PDGF-BB, SE-CAD and inflammatory factors were observed in the Obs group (P < 0.05). The toxic and side effects were significantly lower and the 1-year survival rate and patients' QOL after 6 months of treatment were significantly higher in the Obs group compared with the Con group (P < 0.05). Conclusion: GEM combined with DDP can provide more clinical benefits for patients with recurrent/metastatic advanced NPC, with less side effects, high tolerance and significant efficacy, which can be further promoted in clinical use.

Identification of MATN3 as a Novel Prognostic Biomarker for Gastric Cancer through Comprehensive TCGA and GEO Data Mining.

Gastric cancer (GC) is still a vital malignant cancer across the world with unsatisfactory prognostic results. Matrilin-3 (MATN3) is a member of the extracellular matrix (ECM) protein family. The present research intends to explore the expression level of MATN3 in patients with GC and to explore the prognosis significance of MATN3. In this study, we observed that the MATN3 expression was remarkably upregulated in GC samples in contrast to noncancer samples. Clinical analyses unveiled that high MATN3 expression was related to age, tumor status, and clinical stages. Survival analyses unveiled that patients with high MATN3 expression displayed a poorer overall survival and progression-free survival than those with low MATN3 expression. The AUC of the relevant ROC curve for 1 year, 3 years, and 5 years of survival is 0.571, 0.596, and 0.720, separately. Multivariate assays revealed that MATN3 expression and stage were independent predictors of poor prognosis of GC patients. A meta-analysis unveiled that high MATN3 expression was tightly associated with better overall survival. Overall, our data indicated that MATN3 may have a diagnostic and prognostic value for patients with advanced gastric cancer and assist to improve clinical outcomes for GC patients.