ABSTRACT
Circular RNAs (circRNAs) showing unusual expressions have been discovered in pancreatic adenocarcinoma (PAAD). However, the functions and underlying mechanisms of these circRNAs still remain largely unclear. Our current study discovered a notable increase in the expression of circRNA hsa_circ_0002395 (circ_0002395) in both PAAD tissues and cell lines. This up-regulation of circ_0002395 was found to be associated with larger tumor sizes and lymph node metastasis. Furthermore, our findings showed that circ_0002395 facilitated aerobic glycolysis and cell proliferation in PAAD cells by regulating the miR-548c-3p/PDK1 axis. Mechanistically, we identified circ_0002395 as a competing endogenous RNA (ceRNA) that sponged miR-548c-3p, thereby promoting PDK1 expression and aerobic glycolysis, and ultimately resulting in the enhancement of cell proliferation. Our findings found that circ_0002395 promoted proliferation of PAAD cells by enhancing PDK1 expression and aerobic glycolysis by sponging miR-548c-3p.
Subject(s)
Adenocarcinoma , MicroRNAs , Pancreatic Neoplasms , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/genetics , Adenocarcinoma/genetics , Pancreatic Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , GlycolysisABSTRACT
Increasing studies indicate that circular RNAs (circRNAs) play critical roles in tumor metabolism of multiple cancers. However, the contribution of circRNAs in glutamine metabolism of esophageal squamous cell carcinoma (ESCC) remains elusive. The objective of this research was to investigate the role and mechanism of circRNA hsa_circ_0001093 (circ_0001093) in the glutamine metabolism and tumorigenesis of ESCC. Circ_0001093, microRNA-579-3p (miR-579-3p) and glutaminase (GLS) expressions in ESCC tissues and cell lines were measured by qRT-PCR, tissue array or Western blot. Cell proliferation, invasion and migration were assessed by CCK-8 or transwell assays. Glutamine consumption, glutamate and ATP production were detected by indicated assay kits. The relationships between circ_0001093 and miR-579-3p or GLS mRNA were investigated by bioinformatics analysis, RNA pull-down, luciferase reporter and RNA immunoprecipitation (RIP) assays. Here, we found that circ_0001093 expression was up-regulated in ESCC tissues and cell lines. Increased circ_0001093 expression predicted an unfavourable prognosis, and was associated with the lymph node metastasis, TNM staging and tumor size in ESCC tissues. Circ_0001093 knockdown suppressed cell proliferation, invasion, migration and glutamine metabolism of ESCC cells, while circ_0001093 over-expression showed the opposite effects. Mechanistically, circ_0001093 acted as a competing endogenous RNA (ceRNA) by sponging miR-579-3p, thereby increasing GLS expression. Furthermore, the inhibitory effects of circ_0001093 knockdown on the invasion, migration and glutamine metabolism were partly rescued by miR-579-3p inhibition or GLS over-expression in ESCC cells. Additionally, miR-579-3p expression was down-regulated in ESCC tissues, while GLS expression was up-regulated. In conclusion, this study first provides evidence that the circ_0001093/miR-579-3p/GLS regulatory network can affect glutamine metabolism and malignant phenotype of ESCC, which can further impact ESCC progression.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , MicroRNAs , Cell Line, Tumor , Cell Movement , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , Gene Expression Regulation, Neoplastic , Glutaminase/genetics , Glutaminase/metabolism , Glutamine/genetics , Glutamine/metabolism , Humans , MicroRNAs/metabolismABSTRACT
BACKGROUND: Circular RNAs (circRNAs) or cholesterol metabolism have been demonstrated to participate in stomach adenocarcinoma (STAD) progression. However, the relationship between circRNAs and cholesterol metabolism in STAD and its underlined mechanism remain unclear. METHODS: RNA and protein expression levels were detected by qRT-PCR and Western blot. Cell proliferation was assessed by CCK-8, EdU incorporation and colony formation assays. Total cholesterol (TC) and free cholesterol (FC) levels were measured by the corresponding kits. The relationships between circ_0000182 and miR-579-3p or squalene epoxidase (SQLE) mRNA were investigated by bioinformatics analysis, RNA-RNA pull-down, luciferase reporter and RIP assays. RESULTS: We found that circ_0000182 expression was significantly up-regulated in both STAD tissues and cell lines, and high circ_0000182 expression was correlated with increased tumor size. Circ_0000182 promoted cell proliferation and cholesterol synthesis of STAD cells. Accordingly, cell proliferation, cholesterol synthesis and SQLE expression were significantly inhibited by circ_0000182 knockdown in STAD cells, and these effects were partly reversed by miR-579-3p inhibition or SQLE over-expression. Furthermore, we identified that circ_0000182 acted as a competing endogenous RNA (ceRNA) by sponging miR-579-3p, thereby facilitating SQLE expression, cholesterol synthesis and cell proliferation. CONCLUSION: Circ_0000182 promotes cholesterol synthesis and proliferation of STAD cells by enhancing SQLE expression via sponging miR-579-3p.
ABSTRACT
CircRNAs have been found to play crucial roles in the metabolism and progression of cancers, but their roles and mechanisms in esophageal squamous cell carcinoma (ESCC) have not been fully elucidated. This work is aimed to explore the role and mechanism of hsa_circ_0000705 (circ_0000705) in ESCC. Circ_0000705 expression was up-regulated in ESCC tissues and cell lines, and high circ_0000705 expression was correlated with poor survival. Circ_0000705 facilitated cell proliferation, invasion, migration and proline metabolism of ESCC cells. The inhibitory effects of circ_0000705 knockdown on cell invasion, migration and proline metabolism were partly rescued by miR-621 inhibition or PYCR1 over-expression. Furthermore, circ_0000705 expression is negatively correlated with miR-621 expression, and positively correlated with PYCR1 in ESCC tissues. Mechanistically, circ_0000705 acted as a ceRNA by sponging miR-621, thereby facilitating PYCR1 expression in ESCC cells. In conclusion, circ_0000705 promoted proline metabolism and malignant progression of ESCC by regulating the miR621/PYCR1 axis.