Construction and analysis of the ceRNA network hsa_circ_0031968/miR-3611/GCG in lung adenocarcinoma.

BACKGROUND: A competitive endogenous RNA (ceRNA) network was constructed to examine the potential mechanisms of circular RNAs (circRNAs) in lung adenocarcinoma (LUAD). METHODS: LUAD-related data sets were obtained from the Gene Expression Omnibus (GEO) database and screened for differentially expressed circRNAs (DECs) and differentially expressed microRNAs (DEMs). We identified the target microRNAs (miRNAs) regulated by the DECs and the potential target genes of the miRNA. The basic structure of the DECs were analyzed and enrichment analyses were conducted to determine the function of the circRNA. The Kaplan-Meier method for survival analysis was used to examine the clinical data from The Cancer Genome Atlas (TCGA) database. A protein-protein interaction (PPI) network was constructed to determine the hub genes. The relative expression of the RNA molecules on the ceRNA axis was verified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. RESULTS: A total of 17 DECs and 237 DEMs were selected for analysis. After reviewing the cancer-specific circRNA database (CSCD), 10 circRNAs were identified. The 432 target miRNAs were screened by circRNA interactome (CRI) and cross-referenced with the DEMs to obtain 126 miRNAs of interest. The expression of miR-3611, which is regulated by hsa_circ_0031968, was found to significantly affect the survival and prognosis of patients with LUAD (P≤0.05). The target gene function of hsa_circ_0031968 was determined to be mainly enriched in SMAD binding, and the signaling pathway was primarily enriched in miRNAs related to cancer. The TCGA database screened out 2,484 differentially expressed mRNAs (DEmRNAs) and intersection analysis with the target gene of miR-3611 revealed 1 gene, namely the proglucagon gene (GCG). Therefore, we chose the hsa_circ_0031968/miR-3611/GCG axis for further research. The expression of GCG was determined to be associated with a poorer survival rate and higher T stage in LUAD patients. Finally, 17 hub genes that interact with GCG were identified. CONCLUSIONS: The ceRNA regulatory network hsa_circ_0031968/miR-3611/GCG was successfully constructed and this provided novel insights into the identification of biomarkers and the pathogenesis of LUAD. This knowledge will contribute to the early diagnosis and development of potential treatment for patients with LUAD.

The Long Noncoding RNA Linc01833 Enhances Lung Adenocarcinoma Progression via MiR-519e-3p/S100A4 Axis.

INTRODUCTION: Lung cancer (LC) is among the most prevalent malignancies worldwide, with extremely high morbidity and mortality rates. Mounting evidence has suggested that the abnormally expressed long noncoding RNA (lncRNA) in lung cancer tissues may play vital roles in tumor progression. In the present research, we aimed to examine the functions and underlying mechanism of linc01833 in lung adenocarcinoma (LUAD). METHODS: qRT-PCR was employed to determine transfection efficiency. CCK-8, transwell invasion assay, Western blotting analysis and qRT-PCR were used to detect proliferation as well as migration of different LUAD cell lines, and were also applied to determine the changes during epithelial-mesenchymal transformation (EMT). Afterwards, bioinformatics and dual-luciferase reporter assay were utilized to explore and to identify the potential corresponding targets of linc01833 and miR-519e-3p. RESULTS: Linc01833 OE can significantly improve proliferation as well as invasion ability of LC cells and promote the EMT process. Dual-luciferase reporter assay demonstrated that linc01833 could directly bind to miR-519e-3p, thereby inhibiting its expression. Further experiments showed that S100A4 was a direct target of miR-519e-3p. Rescue assay demonstrated that linc01833 acted on the miR-519e-3p/S100A4 axis. CONCLUSION: We verified the mechanism of linc01833 in promoting infiltration and metastasis in LUAD. To be specific, linc01833 can function as a competitive endogenous RNA (ceRNA) to adsorb miR-519e-3p through a sponge and regulate S100A4 in lung cancer, thereby being involved in LUAD progression. Collectively, our research provides new insights towards the in-depth understanding of LC progression mechanisms.

MicroRNA let-7i Inhibits Histone Lysine Demethylase KDM5B to Halt Esophageal Cancer Progression.

Recent studies have suggested that microRNA let-7i is a tumor suppressor in human cancers, including esophageal cancer, but its underlying mechanism is not yet fully understood. We investigated the role and mechanisms of let-7i in the progression of esophageal cancer. We first showed that let-7i was downregulated in esophageal cancer tissues and cells and then linked its low expression to cancer progression. Bioinformatic analysis predicted KDM5B as a target gene of let-7i, which was confirmed by a dual-luciferase reporter assay. Loss- and gain-of function approaches were adopted to examine the interactions of let-7i, KDM5B, SOX17, and GREB1 in vitro and in vivo. Overexpression of let-7i suppressed esophageal cancer cell proliferation and invasion and promoted apoptosis. Mechanistic investigation showed that let-7i targeted and inhibited KDM5B expression, whereas KDM5B enhanced H3K4me3 at the SOX17 promoter region. Overexpression of let-7i suppressed the expression of GREB1 in esophageal cancer cells by regulating the KDM5B/SOX17 axis in vivo and in vitro. Taken together, our findings reveal the tumor-suppressive properties of let-7i in esophageal cancer in association with an apparent KDM5B-dependent SOX17/GREB1 axis. This study offers a potential prognostic marker and therapeutic target for esophageal cancer.