Gastric cancer (GC) is the second leading cause of cancer-related death worldwide. Recently, accumulating evidence suggests that microRNAs (miRNAs) play prominent roles in tumorigenesis and metastasis. Here, we confirmed that miR-25 was significantly increased in human GC tissues and cell lines. Forced expression of miR-25 remarkably enhanced cell proliferation, migration, and invasion in GC cells, whereas inhibition of miR-25 by inhibitor caused significant suppression of proliferation and significant increase of apoptosis. Moreover, inhibition of miR-25 significantly decreased migration and invasion of GC cells. Finally, reversion-inducing-cysteine-rich protein with kazal motifs (RECK) was found to be a target of miR-25. Overexpression of RECK could significantly reverse the oncogenic effect of miR-25. Taken together, miR-25 might promote GC cells growth and motility partially by targeting RECK.
Gastric cancer remains one of the most dangerous cancers, bringing suffering and economic burden to people worldwide. Long noncoding RNAs (lncRNAs) exhibit great potentials for targeted therapy of various cancers. In this investigation, we tested mechanisms by which LINC01021 may regulate gastric cancer progression. We collected gastric cancer tissues and procured cell lines to explore the potential factors by which LINC01021 had effects on angiogenesis, invasion, and migration, by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Transwell assay, and western blot analysis. Relationships among LINC01021, Caudal-type homeobox 2 (CDX2), and KISS1 were validated by dual-luciferase gene reporter, RNA pull-down, and RNA immunoprecipitation assays. Additionally, a murine model was developed to further explore the impact of LINC01021 on tumors in vivo. LINC01021 was upregulated in gastric cancer tissues and cells. LINC01021 regulated KISS1 through CDK2, which promoted phosphorylation and nuclear export in CDX2. Inhibition of LINC01021 suppressed the tumorigenesis of gastric cancer. Further, silencing LINC01021 exerted an inhibitory effect on cancer cell migration, invasion, and angiogenesis by promoting the binding between CDX2 and KISS1, while inhibiting that between CDK2 and CDX2. Taken altogether, high LINC01021 expression in gastric cancer promotes malignant cell migration and angiogenesis by downregulation of KISS1 through CDK2-mediated CDX2 phosphorylation.
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.
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