Dataset Information

LncRNA LINC00460 Silencing Represses EMT in Colon Cancer through Downregulation of ANXA2 via Upregulating miR-433-3p.

ABSTRACT: Colon cancer (CC), one of the major causes of tumor-associated death, is often presented with a heterogenic pool of cells with unique differentiation patterns. This study explored the functions that LINC00460 displayed in CC by regulating microRNA-433-3p (miR-433-3p) and Annexin A2 (ANXA2). LINC00460 expression was either silenced or overexpressed in HCT-116 and LOVO cells to explore the functional roles of LINC00460 in CC. The relationship between miR-433-3p and LINC00460/ANXA2 was analyzed using dual-luciferase reporter assay, RNA-pull down, and RNA immunoprecipitation (RIP) assays. Cell proliferation, metastasis, invasion, and apoptosis were examined in vitro, and tumorigenicity was evaluated in vivo following LINC00460 silencing. Additionally, the regulatory mechanisms were investigated using LINC00460 and ANXA2 gain- or loss-of-function experiments. We found that LINC00460 was expressed highly in CC. Downregulation of LINC00460 inhibited cell invasion and proliferation in vitro and restrained tumor growth in vivo. Moreover, LINC00460 was able to specifically bind to miR-433-3p to increase the expression of ANXA2. Furthermore, LINC00460 downregulated the E-cadherin expression and upregulated the vimentin and N-cadherin expression by upregulating ANXA2, therefore inducing epithelial-mesenchymal transition. These findings suggested that LINC00460 might function as an oncogenic long non-coding RNA (lncRNA) in CC development and could be explored as a potential biomarker and therapeutic target for CC.

SUBMITTER: Hong W

PROVIDER: S-EPMC7019044 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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lncRNA LINC00460 Silencing Represses EMT in Colon Cancer through Downregulation of ANXA2 via Upregulating miR-433-3p.

Hong Weiwen W Ying Hongan H Lin Feng F Ding Ruliang R Wang Weiya W Zhang Meng M

Molecular therapy. Nucleic acids 20191218

Colon cancer (CC), one of the major causes of tumor-associated death, is often presented with a heterogenic pool of cells with unique differentiation patterns. This study explored the functions that LINC00460 displayed in CC by regulating microRNA-433-3p (miR-433-3p) and Annexin A2 (ANXA2). LINC00460 expression was either silenced or overexpressed in HCT-116 and LOVO cells to explore the functional roles of LINC00460 in CC. The relationship between miR-433-3p and LINC00460/ANXA2 was analyzed usi ...[more]

PMID: 32069703

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Project description:BackgroundPancreatic cancer is a malignant tumor and ranks the sixth in incidence among cancers. Circular RNA (circRNA) has been reported to regulate the progression of pancreatic cancer. However, the effects of circ-membrane bound O-acyltransferase domain containing 2 (circ-MBOAT2) on regulating pancreatic cancer process were unclear.MethodsThe expression levels of circ-MBOAT2, microRNA-433-3p (miR-433-3p) and glutamic-oxaloacetic transaminase 1 (GOT1) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). GOT1 protein expression was determined by western blot analysis. Cell proliferation was illustrated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and cell colony formation assay. Cell apoptosis was demonstrated by flow cytometry analysis. Cell invasion and migration were investigated by transwell invasion and wound-healing assays. Glutamine catabolism was explained by detecting glutamine consumption, alpha ketoglutarate (α-KG) production and glutamate production. In vivo assay was performed to illustrate the impacts of circ-MBOAT2 silencing on tumor formation in vivo. The binding relationship between miR-433-3p and circ-MBOAT2 or GOT1 was predicted by circinteractome or starbase online databases, and identified by dual-luciferase reporter assay.ResultsCirc-MBOAT2 and GOT1 expression were significantly upregulated, while miR-433-3p expression was downregulated in pancreatic cancer tissues and cells compared with normal pancreatic tissues or cells. Circ-MBOAT2 silencing repressed cell proliferation, migration, invasion and glutamine catabolism, whereas promoted cell apoptosis in pancreatic cancer. Additionally, circ-MBOAT2 acted as a sponge of miR-433-3p, which was found to be associate with GOT1. MiR-433-3p inhibitors hindered circ-MBOAT2 silencing-mediated impacts on pancreatic cancer progression and glutamine catabolism. Furthermore, circ-MBOAT2 silencing repressed tumor formation in vivo.ConclusionCirc-MBOAT2 modulated tumor development and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer. This finding suggests that circ-MBOAT2 may be a therapeutic target for pancreatic cancer.

Project description:Dickkopf-1 (DKK1) is a powerful antagonist of canonical WNT signaling pathway, and is regarded as a biomarker for osteoporosis. Its expression is highly correlated with bone mass and osteoblasts maturation. In this study, mouse primary bone marrow cells and osteoblast cell lines were used. Luciferase reporter assay and western blotting methods were employed to validate if miRNA-433-3p epigenetically regulated DKK1 translation. Rat bone marrow derived osteoblasts were infected with lentivirus vector in which miR-433-3p was constructed. The authors constructed lentivirus mediated miRNA-433-3p stable expression and examined the alkaline phosphatase (ALP) activity and mineral deposition level in vitro. In situ hybridization method was used to observe miR-433-3p in primary osteoblasts. We built up an OVX rat model to mimic postmenopausal osteoporosis, and found aberrant circulating miR-433-3p and miR-106b, which were not reported previously. Results showed that miR-433-3p potentially regulated DKK1 mRNA, Furthermore, the correlation of serum DKK1 with circulating miR-433-3p level was significant (r = 0.7520, p = 0.046). In the luciferase reporter assay, we found that miR-433-3p siRNA decreased luminescence signal, indicating direct regulation of miR-433-3p on DKK1 mRNA. When the miR-433-3p binding site in DKK1 3'UTR was mutant, such reduction was prohibited. Western blotting result validated that miR-433-3p inhibited over 90% of DKK1 protein expression. Similarly, the change of protein expression was not observed in mutant group. The stable expression of lentivirus mediated miR-433-3p increased ALP activity and mineralization both in human and rat derived immortalized cells. We found that primary osteoblasts had higher miR-433-3p level compared with immortal cells through real-time PCR, as well as in situ hybridization experiment. Conclusively, our findings further emphasized the vital role of miR-433-3p in DKK1/WNT/?-catenin pathway through decreasing DKK1 expression and inducing osteoblasts differentiation.

Dataset Information

LncRNA LINC00460 Silencing Represses EMT in Colon Cancer through Downregulation of ANXA2 via Upregulating miR-433-3p.

Publications

lncRNA LINC00460 Silencing Represses EMT in Colon Cancer through Downregulation of ANXA2 via Upregulating miR-433-3p.

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