Background: Ferroptosis is a novel iron-dependent cell death, and an increasing number of studies have shown that long non-coding RNA (lncRNAs) are involved in the ferroptosis process. However, studies on ferroptosis-related lncRNAs in lung squamous cell carcinoma (LUSC) are limited. In addition, the prognostic role of ferroptosis-related lncRNAs and their relationship with the immune microenvironment and methylation of LUSC is unclear. This study aimed to investigate the potential prognostic value of ferroptosis-related lncRNAs and their involved biological functions in LUSC. Methods:The Cancer Genome Atlas (TCGA) database and the FerrDb website were used to obtain ferroptosis-related genes for LUSC. The "limma" R package and Pearson analysis were used to find ferroptosis-related lncRNAs. The biological functions of the characterized lncRNAs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We evaluated the prognostic power of this model using Kaplan-Meier analysis, receiver operating characteristic (ROC), and decision curve analysis (DCA). Univariate and multifactor Cox (proportional-hazards) risk model and a nomogram were produced using risk models and clinicopathological parameters for further verification. In addition, the relationship between characterized lncRNAs and tumor immune infiltration and methylation was also discussed. Results:We identified 29 characterized lncRNAs to produce prognostic risk models. Kaplan-Meier analysis revealed the high-risk group was associated with poor prognosis in LUSC (P<0.001), and ROC (AUC =0.658) and DCA suggested that risk models could predict prognosis. Univariate and multifactorial Cox as well as nomogram further validated the prognostic model (P<0.001). Gene set enrichment analysis (GSEA) showed that the high-risk group was associated with pro-tumor pathways and high-frequency mutations in TP53 were present in both groups. Single sample gene set enrichment analysis (ssGSEA) showed significant differences in immune cell infiltration subtypes and corresponding functions between the two groups. Some immune checkpoint and methylation-related genes were significantly different between the two groups (P<0.05).

Bladder cancer (BCa) is one of the most common tumors of the genitourinary system. However, the detailed molecular mechanism of BCa progression is still unclear. Recently, an increasing number of studies have demonstrated that circular RNAs (circRNAs) play a critical role in the tumorigenesis and progression of BCa. In this article, we showed that circSHPRH expression was obviously decreased in BCa tissues, compared with adjacent normal tissues. Moreover, a low circSHPRH level was positively correlated with a high grade, a high pathological stage, lymphatic metastasis and an unfavorable prognosis for BCa patients. Cell function studies indicated that silencing circSHPRH dramatically increased the proliferation, migration and invasion of BCa cells. Animal experiments revealed that circSHPRH overexpression repressed tumor growth. Mechanistic studies demonstrated that circSHPRH could combine with miR-942 and serve as a sponge of miR-942, which targets BARX2 in BCa cells. Rescue experiments showed that suppression of miR-942 or BARX2 overexpression could significantly abrogate the promoting effects of circSHPRH silencing on BCa cell proliferation and invasion. Furthermore, circSHPRH overexpression partly eliminated the suppressive effects of miR-942 on BARX2 expression. In addition, circSHPRH knockdown promoted activation of the Wnt/β-catenin signaling pathway by regulating BARX2. Taken together, our findings indicate that circSHPRH serves as a sponge of miR-942 to inhibit BCa progression by upregulating BARX2 expression, thereby inhibiting the Wnt/β-catenin signaling pathway.

Background Ferroptosis is a kind of programmed cell death that is characterized by iron dependence. It differs from apoptosis, necrosis, autophagy, pyroptosis, and other types of cell death. Some studies have found that most of the genes involved in the regulation of ferroptosis or act as markers of ferroptosis are related to the poor prognosis of cancer patients. Methods This study evaluated the expression, mutation, and copy number variation (CNV) of 60 previously reported ferroptosis genes in breast cancer samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Unsupervised clustering of breast cancer samples with ferroptosis genes was performed, followed by enrichment analysis with Gene Set Variation Analysis (GSVA), mutation display, and correlation analysis of clinical characteristics. Based on the analysis of differences among groups, the ferroptosis-related genes were identified, and the consistent clustering of breast cancer samples was performed. The characteristic genes were screened by stochastic forest algorithm and COX analysis, and a ferroptosis score (ferr.score) model was constructed to evaluate the prognosis of breast cancer patients. Results Copy number amplification and deletion of ferroptosis genes are common in breast cancer. Breast cancer patients grouped by ferroptosis gene clusters showed significant differences in survival, immune cell infiltration, and enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. The ferroptosis-related differential genes were identified by comparison among clustering groups of ferroptosis gene. Characteristic genes were screened from these ferroptosis-related differential genes to construct the ferr.score model. The scoring model could accurately distinguish and predict the survival prognosis and immunotherapy efficacy in breast cancer patients. Conclusions Ferroptosis plays an important role in the occurrence and development of tumors. According to the ferr.score model, the breast cancer samples can be divided into two groups with significantly different prognoses. These results provide novel insights and ideas for immunotherapy in breast cancer patients.

Circular RNAs (circRNAs) are recognized as a novel type of single-stranded endogenous noncoding RNA molecule with the characteristics of tissue specificity, sequence conservation and structural stability. Accumulating studies have shown that circRNAs play a unique biological role in different kinds of diseases. CircRNAs can affect tumor proliferation, migration, metastasis and other behaviors by modulating the expression of downstream genes. CircSMARCA5, an example of a circRNA, is dysregulated in various noninfectious diseases, such as tumors, osteoporosis, atherosclerosis and coronary heart disease. Furthermore, recent studies have demonstrated that circSMARCA5 is associated with the occurrence and development of a variety of tumors, including gastric cancer, glioblastoma, hepatocellular carcinoma, multiple myeloma, colorectal cancer, breast cancer and osteosarcoma. Mechanistically, circSMARCA5 primarily acts as a sponge of miRNAs to regulate the expression of downstream genes, and can serve as a potential biomarker for the diagnosis of malignant tumors. This review summarizes the biological roles of circSMARCA5 and its molecular mechanism of action in various diseases. Moreover, the meta-analysis of some publications showed that the expression of circSMARCA5 was significantly correlated with the prognosis of patients and tumor TNM stage, showing that circSMARCA5 has the potential to be a prognostic marker.

BackgroundBladder cancer (BCa) is a malignant tumor that occurs in the bladder mucosa with high mortality. Circular RNAs (circRNAs), newly discovered noncoding RNAs, are associated with the occurrence and development of BCa. However, the effects of circRNAs in BCa have not been fully elucidated. Through the GEO (Gene Expression Omnibus) database, an abnormally expressed circular RNA, circHGS (hsa_circ_0004721), was rst identi ed in BCa. In this study, we clari ed the roles and potential mechanism of circHGS in BCa progression. MethodsThe level of circHGS in tissue and cell was assessed by qRT-PCR. The proliferation, migration and invasion of BCa cells were detected by CCK8, colony formation assay, wound-healing assay, and Transwell assays, respectively. The interaction between circHGS/VEGFC and miR-513a-5p was detected by dual luciferase and qRT-PCR. VEGFC protein level was detected by western blotting. Nude mouse xenograft model was used to clarify the role of circHGS in tumor growth in vivo. ResultsCircHGS, originating from the HGS gene, is upregulated in BCa tissues compared to normal tissues.Functionally, silencing of circHGS apparently suppressed BCa cell proliferation, migration and invasion, but circHGS overexpression showed the opposite result. In vivo experiments also suggested that knockdown of circHGS suppressed tumor growth. Mechanistically, circHGS functions as a sponge of miR-513a-5p to elevate VEGFC expression and activate the AKT/mTOR signaling pathway, ultimately promoting BCa progression. ConclusionOur ndings indicated that circHGS promotes BCa progression via the miR-513a-5p/VEGFC/AKT/mTOR pathway and can be a promising therapeutic target of BCa.

Background Lung adenocarcinoma (LUAD) is a malignancy with a high global incidence and cancer-related mortality rate. Although various clinical trials have improved the prognosis of LUAD patients, the 5-year survival rate is still low. This study aimed to improve the prognosis of LUAD patients through molecular subtype-based precision therapy. Methods LUAD RNA sequencing (RNA-seq) data obtained from online database was used to screen for differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) combined with univariate and multifactorial COX analysis was used to identify hub prognostic genes. Based on these genes, pam clustering classified LUAD into two subtypes. The ESTIMATE, Immunophenoscore (IPS), and Microenvironment Cell Populations-counter (MCP-counter) algorithm were applied to determine the microenvironmental purity and immune response of the two subtypes. Genomic enrichment analysis (GSEA) was performed to analyze the function. Mutational difference was also explored. The effects of cisplatin and FASNi on gene expression were examined by RT-PCR. Results The results showed that LUAD patients could be divided into two subtypes. The survival rate of patients in cluster 2 was signifcantly higher than that in cluster 1 (P = 7.9e-3). Patients in cluster 2 had more immune cell infiltration, higher microenvironmental component, and higher rate of EGFR mutations (P < 0.05). In contrast, patients in cluster 1 had more fibroblast infiltration and high rate of NTRK3 mutations (P < 0.05). In addition, functional analysis suggested cluster 1 was associated with Nucleotide sequence repair, while cluster 2 mainly related to lipid metabolism and angiogenic pathways (FDR < 0.25). RT-PCR indicated that cluster1-related model genes were associated with cisplatin, cluster2-related genes were associated with EGFR-targeted therapy and lipid metabolism inhibitors. Conclusions This study showed patients in cluster 1 may benefit from anti-Nucleotide repair therapies such as platinum, radiotherapy, targeting fibroblasts, and targeting NTRK3, while patients in cluster 2 benefit from immunotherapy, anti-angiogenic, targeting lipid metabolism, and targeting EGFR therapy. This study may provide new insights to improve the overall prognosis of LUAD patients through molecular subtype-based precision therapy.

Circular RNA (circRNA) molecules are noncoding RNAs with ring-like structures formed by covalent bonds and are characterized by no 5′caps or 3′polyadenylated tails. Increasing evidence shows that circRNAs may play an important role in tumorigenesis and cancer metastasis. Circ-SHPRH originates from exons 26–29 of the SHPRH gene, and it is closely associated with human cancers. We searched PubMed, Web of Science, and Embase databases for relevant literatures until 24 December 2022. Eighteen research papers were included in this review, and 11 papers were selected for meta-analysis after screening. Three eligible published studies about circ-SHPRH were enrolled based on their tumor diagnosis aspect, 7 eligible published studies were related to overall survival (OS), and 3 eligible published studies were related to tumor grade. Many studies have shown that circ-SHPRH acts as a miRNA sponge or encodes a protein to regulate downstream genes or signal pathways, and exerts specific biological functions that affect the proliferation, invasion, and apoptosis of cancer cells. Meta-analysis showed that patients with high expression of circ-SHPRH had better OS (HR = 0.53, 95% CI 0.38–0.74, p-value &lt;0.05) and lower TNM stage (HR = 0.33, 95% CI 0.18–0.62, p-value = 0.001). In addition, circ-SHPRH has potential diagnostic value (AUC = 0.8357). This review will help enrich our understanding of the role and mechanism of circ-SHPRH in human cancers. Circ-SHPRH has the potential to be a novel diagnostic and prognostic biomarker for various solid cancers.