hsa_circ_001653 up-regulates NR6A1 expression and elicits gastric cancer progression by binding to microRNA-377.

What is the central question of this study? Does hsa_circ_001653 influence the development of gastric cancer (GC) and if so how? What is the main finding and its importance? Bioinformatics analysis revealed the presence of differentially expressed hsa_circ_001653 in GC and adjacent normal tissues, and this was strongly related to the pathology of patients with GC. Knockdown of hsa_circ_001653 suppressed the proliferation, invasion and migration of GC cells, while inducing cell apoptosis via miR-377-mediated NR6A1 inhibition. The effect of hsa_circ_001653 and miR-377 on tumour growth in GC was further confirmed in vivo. Gastric cancer (GC) is one of the leading causes of human mortality through malignant tumours. Circular RNAs (circRNAs) have been identified as binding to microRNAs (miRNAs) to modulate the progression of tumours. This study explores the role of hsa_circ_001653, a newly identified circRNA, in the development of GC. hsa_circ_001653 expression was measured in 86 paired normal and tumour tissues surgically resected from GC patients. Cross-talk between hsa_circ_001653 and microRNA-377 (miR-377)/nuclear receptor subfamily 6, group A, member 1 (NR6A1) was assessed using bioinformatics analysis, dual-luciferase reporter assay, Ago2 immunoprecipitation and western blot analysis. A series of functional experiments were carried out to elucidate the role of hsa_circ_001653 in GC cell proliferation, invasion, migration and apoptosis, and its underlying molecular mechanisms. Nude mice were inoculated with GC cells for in vivo analysis. hsa_circ_001653 was found to be an up-regulated circRNA in GC tissues and cells. Down-regulation of hsa_circ_001653 inhibited GC cell proliferation, migration and invasion, while stimulating cell apoptosis. hsa_circ_001653 was found to bind to miR-377, which targeted NR6A1 and repressed its expression. Inhibition of miR-377 and overexpression of NR6A1 restored the proliferation, migration and invasion in GC cells lacking hsa_circ_001653. Furthermore, inhibition of hsa_circ_001653 attenuated tumour growth in nude mice inoculated with GC cells. Collectively, the demonstration that hsa_circ_001653 exerts its anticancer effects by regulating the miR-377-NR6A1 axis increases our understanding of gastric cancer pathophysiology. The findings uncover new potential therapeutic targets for GC.

Zhou W ，Jiang R ，Wang Y ，Li Y ，Sun Z ，Zhao H ... -  《-》

Oncogenic circular RNA Hsa-circ-000684 interacts with microRNA-186 to upregulate ZEB1 in gastric cancer.

Circular RNAs (circRNAs) function as modulators of microRNAs (miRNAs) and are often involved in cancer progression. This study aims to investigate the underlying mechanism by which circRNA hsa-circ-000684 promotes the progression of gastric cancer (GC). Expression of hsa-circ-000684 and that of ZEB1 mRNA were elevated while microRNA-186 (miR-186) expression was downregulated in GC cell lines and clinical tissues. In addition, the effects of hsa-circ-000684 on the proliferation, migration, invasion, and tube formation of GC cells were examined through gain-and loss-of-function experiments. Furthermore, we introduced tumor xenografts into nude mice to better understand these effects in vivo. Either knockdown of hsa-circ-000684 or upregulation of miR-186 inhibited GC cell proliferation, migration, invasion, and tube formation in vitro, and reduced the xenograft tumor growth in nude mice. Moreover, we found that hsa-circ-000684 and ZEB1 directly bound to miR-186. Hsa-circ-000684 increased the expression of ZEB1 by binding to miR-186. The tumor suppressive effects of hsa-circ-000684 knockdown were reversed by inhibition of miR-186. Collectively, our data show that hsa-circ-000684 reduces the miR-186 expression which leads to an increase in the ZEB1 expression and, consequently, promotion of GC progression.

Lin S ，Song S ，Sun R ，Zhang M ，Du Y ，Zhang D ，Xu W ，Wang H ... -  《-》

Circular RNA hsa_circ_0004872 inhibits gastric cancer progression via the miR-224/Smad4/ADAR1 successive regulatory circuit.

Ma C ，Wang X ，Yang F ，Zang Y ，Liu J ，Wang X ，Xu X ，Li W ，Jia J ，Liu Z ... -  《Molecular Cancer》

Circular RNA hsa_circ_0000751 serves as a microRNA-488 sponge to suppress gastric cancer progression via ubiquinol-cytochrome c reductase core protein 2 regulation.

Wang D ，Su F ，Feng M 《-》

Circular RNA-hsa-circ-0000670 promotes gastric cancer progression through the microRNA-384/SIX4 axis.

Circular RNAs (circRNAs), a special type of non-coding RNA molecules, have been addressed to be implicated in gastric cancer progression. The GSE93541 and GSE83521 microarrays found hsa-circRNA-000670 (hsa-circ-0000670) as an up-regulated circRNAin gastric cancer. We mainly investigated the function and molecular mechanisms of hsa-circ-0000670 involved in gastric cancer. The expression of hsa-circ-0000670 was determined by RT-qPCR to be highly expressed in gastric cancer tissues relative to corresponding adjacent normal tissues, as well as in gastric cancer cell lines relative to normal gastric mucosal epithelial cell line. By conducting EdU, scratch test and Transwell assays, hsa-circ-000670 was found to be a tumor promoter by potentiating the proliferative, invasive and migrating capabilities of gastric cancer cells. Consistently, a tumor-promotive role of hsa-circ-000670 was validated in vivo. Dual-luciferase reporter gene and RIP assays identified the binding of hsa-circ-0000670 to microRNA-384 (miR-384) and the binding of miR-384 to sine oculis-related homeobox 4 (SIX4). The oncogenic potential of hsa-circ-0000670 in gastric cancer cells were inhibited by overexpressed miR-384. Mechanistically, SIX4 was targeted by miR-384 and was upregulated in gastric cancer. High SIX4 expression was suggested to correlate with the poor prognosis of gastric cancer patients. Additionally, silencing of SIX4 delayed tumor growth and progression, which were reversed by overexpression of hsa-circ-0000670. Taken together, hsa-circ-0000670 acts as a tumor promotor in gastric cancer progression and might be a potential target for gastric cancer treatment.

Liu P ，Cai S ，Li N 《-》