RESUMEN
BACKGROUND: Pancreatic cancer is a common malignant tumor of the digestive tract. It has a high degree of malignancy and poor prognosis. Finding effective molecular markers has great significance for pancreatic cancer diagnosis and treatment. This study aimed to investigate DLGAP5 expression in pancreatic cancer and explore the possible mechanisms and clinical value of DLGAP5 in tumorigenesis and tumor development. METHODS: Differentially expressed genes were screened using the Gene Expression Omnibus (GEO) data set GSE16515. Gene Ontology (GO)-based functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis were performed on the corresponding proteins of the above genes using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The Kaplan-Meier Plotter database was used to analyze the relationship between differentially expressed genes and pancreatic cancer prognosis. The most prognostic gene, DLGAP5, was screened out, and the Oncomine and gene expression profiling interactive analysis (GEPIA) databases were used to analyze its expression in pancreatic cancer and other cancer tissues. The Cancer Genome Atlas (TCGA) database was used to analyze the overall survival of DLGAP5. Gene set enrichment analysis (GSEA) was performed to explore its possible molecular mechanisms in pancreatic cancer. Furthermore, the biological behavior of DLGAP5 in pancreatic cancer was verified by cell function experiments. RESULTS: A total of 201 significant upregulated differentially expressed genes and 79 downregulated genes were selected. The biological processes with significant enrichment of differential genes included cell adhesion, apoptosis, wound healing, leukocyte migration, angiogenesis. Pathways were mainly enriched in tumor-related signaling pathways such as cancer pathways, the extracellular matrix-receptor interaction pathway, and the p53 signaling pathway. DLGAP5 was significantly expressed in pancreatic cancer, and its expression level had a significant effect on patients' survival time and progression-free survival. GSEA results indicated that DLGAP5 had significantly enriched into signaling pathways such as the cell cycle, the p53 signaling pathway, and oocyte meiosis. The experimental results showed that when we knocked down the expression of DLGAP5 in pancreatic cancer cells, their proliferation ability was significantly inhibited, and their invasion and migration ability significantly decreased. CONCLUSIONS: DLGAP5 can be used as a prognostic indicator for pancreatic cancer and affect the occurrence and development of pancreatic cancer.
RESUMEN
Colorectal cancer (CRC) is one of the most common malignant tumors in the world. With the deepening of people's understanding of CRC at the molecular level, the survival and prognosis of CRC have been significantly improved with the help of surgery, radiotherapy, and chemotherapy, molecular targeted biological therapy and early detection of diseases. The research of different disciplines and the development of multihistological analysis in recent years have proved that the occurrence and development of CRC is a complex biological process with the common action of multiple factors, which involves the huge changes of various histological levels such as the genome, transcriptome, and epigenome. At present, the abnormal expression of protein products in the transcription process has attracted more and more attention. Based on the sensitivity and timeliness of its changes, it has become a hot topic to study the occurrence and development mechanism of CRC through transcriptome changes, so as to provide markers for early diagnosis and prognosis. In recent years, competitive endogenous RNA (ceRNA) has become one of the hot topics in cancer research. The ceRNA hypothesis holds that transcripts such as long noncoding RNA can competitively bind microRNA (miRNA), thus preventing miRNA from binding to messenger RNA (mRNA) and thereby regulating the expression of mRNA. At present, the interaction mechanism of ceRNA in CRC is still unclear, and exploring its interaction relationship is of great significance to elucidate the occurrence and development mechanism of CRC. In this study, we used The Cancer Genome Atlas (TCGA) RNA - seq data of colorectal Cancer and microRnas - seq data to construct colorectal Cancer ceRNA topology network to mine key RNAs that influence the prognosis of colorectal cancer, providing potential RNA biomarkers.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Nowadays, pancreatic cancer (PC) remains the most lethal tumor, partially due to the invasive and treatment-resistant phenotype induced by the extent of hypoxic stress within the tumor tissue. According to previous studies, miR-142/HIF-1α and miR-133a/EGFR could modulate PC cell proliferation under hypoxic and normoxic conditions, respectively. In the present study, FEZF1-AS1, a recently described oncogenic long noncoding RNA, was predicted to target both miR-142 and miR-133a; thus, we hypothesized that FEZF1-AS1 might affect PC cell proliferation through these two axes under hypoxic or normoxic conditions. In PC cell lines, FEZF1-AS1 acted as an oncogene via promoting PC cell proliferation and invasion through miR-142/HIF-1α axis under hypoxic condition; however, FEZF1-AS1 failed to affect the protein levels of HIF-1α and VEGF under the normoxic condition, suggesting the existence of another signaling pathway under normoxic condition. As predicted by an online tool, FEZF1-AS1 could target miR-133a to inhibit its expression; under the normoxic condition, FEZF1-AS1 exerted its effect on PC cell lines through miR-133a/EGFR axis. Taken together, FEZF1-AS1 might be a promising target in controlling the aberrant proliferation and invasion of PC cell lines.