Circ-LDLRAD3 Enhances Cell Growth, Migration, and Invasion and Inhibits Apoptosis by Regulating MiR-224-5p/NRP2 Axis in Gastric Cancer.

BACKGROUND: Emerging as a newly discovered type of noncoding RNAs, circular RNAs have been manifested as a crucial regulator in tumorigenesis of human malignancies, including gastric cancer (GC). Although circ-LDLRAD3 has been revealed as an oncogene in pancreatic cancer, the underlying role of circ-LDLRAD3 in GC remains poorly understood. AIMS: Exploring the underlying function of circ-LDLRAD3 on GC progression. METHODS: Circ-LDLRAD3 expression was detected through RT-qPCR. EdU, colony formation, TUNEL, and transwell assays were performed to analyze the function of circ-LDLRAD3 on GC progression. Luciferase reporter and RIP assays were applied to testify the interaction between circ-LDLRAD, miR-224-5p, and NRP2 in GC. RESULTS: We detected preliminarily the expression of circ-LDLRAD3 and observed a markedly high expression of circ-LDLRAD3 in GC cells. Besides, circ-LDLRAD3 was featured with loop structure. Biological function assays testified that silenced circ-LDLRAD3 inhibited cell proliferation, migration, and invasion capacity but facilitated apoptosis of GC cells. Molecular mechanism assays uncovered that circ-LDLRAD3 combined with miR-224-5p in GC. Moreover, rescue assays delineated that inhibited expression of miR-224-5p could restore the inhibitive influence of circ-LDLRAD3 knockdown on the progression of GC. Moreover, neuropilin 2 (NRP2) was a downstream target of miR-224-5p. Additionally, circ-LDLRAD3 regulated NRP2 expression by sponging miR-224-5p in GC. Furthermore, circ-LDLRAD3 depletion-mediated effect on GC progression could be reversed by overexpressing NRP2. CONCLUSIONS: Circ-LDLRAD3 facilitates GC progression by regulating miR-224-5p/NRP2 axis, providing new insights for the researches of GC treatment.

Circular RNA circ-LDLRAD3 serves as an oncogene to promote non-small cell lung cancer progression by upregulating SLC1A5 through sponging miR-137.

Circular RNAs (circRNAs) are closely associated with the development of non-small cell lung cancer (NSCLC); however, it is still unclear whether circular RNA circ-LDLRAD3 participated in the regulation of NSCLC progression. In this study, we found that circ-LDLRAD3 was high-expressed and miR-137 was low-expressed in NSCLC tissues and cells compared to their normal counterparts, which showed negative correlations in NSCLC tissues. Further experiments validated that miR-137 could be sponged and inhibited by circ-LDLRAD3 in NSCLC cells. In addition, knock-down of circ-LDLRAD3 and miR-137 overexpression promoted NSCLC cell apoptosis, and inhibited cell proliferation and invasion. Similarly, upregulation of circ-LDLRAD3 or miR-137 ablation had opposite effects on the above cell functions. Besides, the glutamine transporter SLC1A5 was validated to be the downstream target of circ-LDLRAD3 and miR-137, and upregulated circ-LDLRAD3 increased SLC1A5 expression levels by downregulating miR-137. Furthermore, the effects of downregulated circ-LDLRAD3 on cell proliferation, apoptosis and mobility were all reversed by knocking down miR-137 and overexpressing SLC1A5. Taken together, this in vitro study found that knock-down of circ-LDLRAD3 inhibited the development of NSCLC by regulating miR-137/SLC1A5 axis.

circ-LDLRAD3 Knockdown Reduces Cisplatin Chemoresistance and Inhibits the Development of Gastric Cancer with Cisplatin Resistance through miR-588 Enrichment-Mediated SOX5 Inhibition.

Background/Aims: Chemoresistance is a common event after cancer chemotherapy, which is associated with the deregulation of circular RNAs (circRNAs). The objective of this study was to clarify the role of circ-LDLRAD3 in cisplatin (DDP)-resistant gastric cancer (GC). Methods: The expression of circ-LDLRAD3, miR-588, and SRY-box transcription factor 5 (SOX5) mRNA was detected by quantitative real-time polymerase chain reaction. Cell viability and the half maximal inhibitory concentration (IC50) value were measured by CCK8 assay. Cell proliferation was assessed by colony formation and EdU assays. Cell apoptosis and cell invasion were assessed by flow cytometry assay and transwell assay, respectively. The expression of SOX5 protein was detected by Western blotting. A xenograft model was established to verify the role of circ-LDLRAD3 in vivo. Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy and the expression of exosome-related proteins. Results: circ-LDLRAD3 was overexpressed in DDP-resistant GC tissues and cells. circ-LDLRAD3 knockdown decreased the IC50 of DDP-resistant cells and suppressed cell proliferation, survival and invasion. miR-588 was a target of circ-LDLRAD3, and miR-588 inhibition attenuated the inhibition of DDP resistance, proliferation, survival and invasion in DDP-resistant GC cells caused by circ-LDLRAD3 knockdown. SOX5 was a target of miR-588, and the inhibition of the DDP resistance, proliferation, survival and invasion of DDP-resistant GC cells by miR-588 restoration was largely rescued SOX5 overexpression. circ-LDLRAD3 knockdown inhibited DDP resistance and tumor growth in vivo. circ-LDLRAD3 was overexpressed in exosomes isolated from DDP-resistant GC cells. Conclusions: circ-LDLRAD3 knockdown reduced DDP resistance and blocked the malignant development of DDP-resistant GC by modulating the miR-588/SOX5 pathway.

Downregulation of circular RNA circ-LDLRAD3 suppresses pancreatic cancer progression through miR-137-3p/PTN axis.

Emerging evidence suggests that dysregulation of circular RNAs (circRNAs) closely associated with cancer progression. In this paper, we focus on exploring the functional role of circ-LDLRAD3 in pancreatic cancer. Gene expression was determined using quantitative reverse transcriptase polymerase chain reaction and Western blot. Cell count kit-8 and 5-ethynyl-2'-deoxyuridine assay were applied to evaluate the proliferation of PANC-1 and SW1990 cells. The migration and invasion of PANC-1 and SW1990 cells were assessed using wound healing assay and transwell invasion assay. Luciferase reporter assay was performed for target validation. The results showed that circ-LDLRAD3 was overexpressed in pancreatic cancer tissues and cell lines. Increased expression of circ-LDLRAD3 was indicative of a poor prognosis in patients with pancreatic cancer. Knockdown of circ-LDLRAD3 repressed the growth of pancreatic cancer in vitro and in vivo. miR-137-3p was identified as a direct target of circ-LDLRAD3. More importantly, upregulation of circ-LDLRAD3 could mitigate the inhibitory effect of miR-137-3p on the proliferation, migration and invasion of pancreatic cancer cells. Besides, circ-LDLRAD3 could regulate the expression of pleiotrophin (PTN) through miR-137-3p. Taken together, knockdown of circ-LDLRAD3 repressed the proliferation, migration and invasion of pancreatic cancer cells through miR-137-3p/PTN axis, providing a new mechanism for pancreatic cancer progression.