Epithelial-to-mesenchymal transition (EMT) is a process that involves the transformation of polarized epithelial cells to attain a mesenchymal phenotype that presents an elevated migratory potential, invasiveness, and antiapoptotic properties. Many studies have demonstrated that EMT is a prominent event that is associated with embryogenesis, tumor progression, metastasis, and therapeutic resistance. The EMT process is driven by key transcription factors (such as Snail, Twist, ZEB, and TGF-β) and several long non-coding RNAs (lncRNAs) in many non-pathological as well as pathological conditions. In the present report, we have comprehensively discussed the oncogenic and tumor suppressor role of lncRNAs and their mechanism of action in the regulation of the EMT process in various cancers such as brain tumors, gastrointestinal tumors, and gynecological and urological tumors. We have also elaborated on the role of lncRNAs in the regulation of EMT-related transcription factors (such as Snail, Twist, ZEB, and TGF-β) and therapeutic response (chemoresistance and radioresistance). Lastly, we have emphasized the role of exosomal lncRNAs in the regulation of EMT, metastasis, and therapeutic response in the aforementioned cancers. Taken together, this review provides a detailed insight into the understanding of role of lncRNAs/exosomal lncRNAs in EMT, metastasis, and therapeutic response in human cancers. 

Long non-coding RNA/epithelial-mesenchymal transition axis in human cancers: Tumorigenesis, chemoresistance, and radioresistance.

YTHDC1 inhibits cell proliferation and angiogenesis in cervical cancer by regulating m6A modification of SOCS4 mRNA

MicroRNAs (miRNAs) are non‑coding RNAs (ncRNAs) that can post‑transcriptionally suppress targeted genes. Dysregulated miRNAs are associated with a variety of diseases. MiR‑181a‑5p is a conserved miRNA with the ability to regulate pathological processes, such as angiogenesis, inflammatory response and obesity. Numerous studies have demonstrated that miR‑181a‑5p exerts regulatory influence on cancer development and progression, acting as an oncomiR or tumor inhibitor in various cancer types by impacting multiple hallmarks of tumor. Generally, miR‑181a‑5p binds to target RNA sequences with partial complementarity, resulting in suppression of the targeted genes of miR‑181a‑5p. However, the precise role of miR‑181a‑5p in cancer remains incompletely understood. The present review aims to provide a comprehensive summary of recent research on miR‑181a‑5p, focusing on its involvement in different types of cancer and its potential as a diagnostic and prognostic biomarker, as well as its function in chemoresistance. 

Role of miR-181a-5p in cancer (Review)

Sepsis is a high mortality disease which seriously threatens human life and health, for which the pathogenetic mechanism still unclear. There is increasing evidence showed that immune and inflammation responses are key players in the development of sepsis pathology. LncRNAs, which act as ceRNAs, have critical roles in various diseases. However, the regulatory roles of ceRNA in the immunopathogenesis of sepsis have not yet been elucidated.In this study, we aimed to identify immune biomarkers associated with sepsis. We first generated a global immune-associated ceRNA (IMCE) network based on data describing interactions pairs of gene-miRNA and miRNA-lncRNA. Afterward, we excavated a dysregulated sepsis immune-associated ceRNA (SPIMC) network from the global IMCE network by means of a multi-step computational approach. Functional enrichment indicated that lncRNAs in SPIMC network have pivotal roles in the immune mechanism underlying sepsis. Subsequently, we identified module and hub genes (CD4 and STAT4) via construction of a sepsis immune-related PPI network. Then, we identified hub genes based on the modular structure of PPI network and generated a ceRNA subnetwork to analyze key lncRNAs associated with sepsis. Finally, 6 lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) that identified as immune biomarkers of sepsis. Moreover, the CIBERSORT algorithm and the infiltration of circulating immune cells types were performed to identify the inflammatory state of sepsis. Correlation analyses between immune cells and sepsis immune biomarkers showed that the LINC00265 was strongly positive correlated with the macrophages M2 (r = 0.77).Collectively, these results may suggest that these lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) played important roles in the immune pathogenesis of sepsis and provide potential therapeutic targets for further researches on immune therapy treatment in patients with sepsis. 

Identification of immune-related lncRNA in sepsis by construction of ceRNA network and integrating bioinformatic analysis

Pulmonary arterial hypertension (PAH) is a rapidly progressing cardiopulmonary disease. It is characterized by increased pulmonary artery pressure and vascular resistance. The most notable histopathological characteristic is vascular remodeling. The changes in the basement membrane (BM) are believed to be related to vascular remodeling. It is crucial to identify potential biomarkers associated with the BM in PAH, to guide its treatment. The microarray datasets GSE117261 and GSE113439 were downloaded from the Gene Expression Omnibus. Two data sets were examined to identify genes associated with the BM by analyzing gene expression changes. Next, we analyzed the relevant genes in the Kyoto Encyclopedia of Genes and Genomes using Gene Ontology and Disease Ontology annotationand conducted pathway enrichment analysis. We conducted a protein-protein interaction network analysis on the genes related to BMs and used the cell cytoHubba plug-in to identify the hub genes. Furthermore, we conducted an immune infiltration analysis and implemented a histogram model. Finally, we predicted and analyzed potential therapeutic drugs for PAH and set up a miRNA network of genetic markers. Six candidate genes related to BMs, namely Integrin Subunit Alpha V, Integrin Subunit Alpha 4, ITGA2, ITGA9, Thrombospondin 1, and Collagen Type IV Alpha 3 Chain, were identified as potential modulators of the immune process in PAH. Furthermore, ginsenoside Rh1 was found to significantly impact drug targeting based on its interactions with the six BM-related genes identified earlier. A novel biomarker related to the BM, which plays a crucial role in the development of PAH, has been identified. 

Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane

As a member of integrin receptor family, ITGAV (integrin subunit α V) is involved in a variety of cell biological processes and overexpressed in various cancers, which may be a potential prognostic factor. However, its prognostic value and potential function in lower-grade glioma (LGG) are still unclear, and in terms of immune infiltration, it has not been fully elucidated. Here, the expression preference, prognostic value, and clinical traits of ITGAV were investigated using The Cancer Genome Atlas database (n = 528) and the Chinese Glioma Genome Atlas dataset (n = 458). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and gene set enrichment analysis (GSEA) were used to explore the biological function of ITGAV. Using R package “ssGSEA” analysis, it was found thatthe ITGAV mRNA expression level showed intense correlation with tumor immunity, such as tumor-infiltrating immune cells and multiple immune-related genes. In addition, ITGAV is associated with some immune checkpoints and immune checkpoint blockade (ICB) and response to chemotherapy. and the expression of ITGAV protein in LGG patients was verified via immunohistochemistry (IHC). ITGAV expression was higher in LGG tissues than in normal tissues (P < 0.001) and multifactor analysis showed that ITGAV mRNA expression was an independent prognostic factor for LGG overall survival (OS; hazard ratio = 2.113, 95% confidence interval = 1.393–3.204, P < 0.001). GSEA showed that ITGAV expression was correlated with Inflammatory response, complement response, KRAS signal, and interferon response. ssGSEA results showed a positive correlation between ITGAV expression and Th2 cell infiltration level. ITGAV mRNA was overexpressed in LGG, and high ITGAV mRNA levels were found to be associated with poor protein expression and poor OS. ITGAV is therefore a potential biomarker for the diagnosis and prognosis of LGG and may be a potential immunotherapy target.

/pdf/integrin-subunit-alpha-v-is-a-potent-prognostic-biomarker-1gnm1etv.pdf

Integrin subunit alpha V is a potent prognostic biomarker associated with immune infiltration in lower-grade glioma

Correction to: Construction of a competitive endogenous RNA network and analysis of potential regulatory axis targets in glioblastoma

lncRNA ZNF674-AS1 inhibits the migration, invasion and epithelial-mesenchymal transition of thyroid cancer cells by modulating the miR-181a/SOCS4 axis

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Integrin subunit alpha V is a potent prognostic biomarker associated with immune infiltration in lower-grade glioma

Correction to: Construction of a competitive endogenous RNA network and analysis of potential regulatory axis targets in glioblastoma

lncRNA ZNF674-AS1 inhibits the migration, invasion and epithelial-mesenchymal transition of thyroid cancer cells by modulating the miR-181a/SOCS4 axis