<p>Circ_0000260 Regulates the Development and Deterioration of Gastric Adenocarcinoma with Cisplatin Resistance by Upregulating MMP11 via Targeting MiR-129-5p</p>

Abstract

Background Cisplatin (CDDP) plays a vital role in the treatment of advanced gastric adenocarcinoma (GAC); however, the development of chemoresistance depletes the overall benefit of CDDP. This study harbored the aim to investigate the role of a novel circular RNA (circRNA), circ_0000260, in DDP-resistant GAC and provide a potential mechanism to explain its function. Methods The morphology of tumor tissues and normal tissues was observed by hematoxylin-eosin (HE) staining. The isolated exosomes were observed and examined using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The expression of circ_0000260, miR-129-5p and matrix metalloproteinase 11 (MMP11) mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of CD63, CD81, fibronectin, vitronectin and MMP11 were detected by Western blot. Cell viability, colony formation, cell apoptosis, migration, invasion and cell adhesion were monitored by cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry assay, scratch assay, transwell assay and cell adhesion assay, respectively. The interaction between miR-129-5p and circ_0000260 or MMP11 predicted by bioinformatics analysis was verified by dual-luciferase reporter assay. Animal experiments were performed in nude mice to explore the role of circ_0000260 in vivo. Results The expression of circ_0000260 was promoted in tumor tissues and serum-derived exosomes of GAC patients, and circ_0000260 expression in CDDP-resistant tumor tissues was higher than that in CDDP-sensitive tumor tissues. Circ_0000260 knockdown lessened CDDP chemoresistance, suppressed cell proliferation, migration, invasion and adhesion, and induced apoptosis. In mechanism, circ_0000260 regulated the expression of MMP11 by targeting miR-129-5p. MiR-129-5p inhibition could reverse the functions of circ_0000260 knockdown, and MMP11 knockdown could also reverse the effects of miR-129-5p inhibition. Besides, circ_0000260 knockdown attenuated CDDP resistance during tumor growth in vivo by regulating the expression of miR-129-5p and MMP11. Conclusion Circ_0000260 regulated CDDP chemoresistance of GAC by promoting MMP11 expression via targeting miR-129-5p.

Circ_0000520 contributes to triple‐negative breast cancer progression through mediating the miR‐1296/ZFX axis

“…HE staining of TNBC tissue and adjacent normal tissue was performed according to the procedures of a previous study, 21 and sections were visualized by a light microscopy with a magnification of 100×.…”

The role and application of small extracellular vesicles in gastric cancer

“… Cisplatin RPS3 protein Promote the chemoresistance of cisplatin-sensitive cells [ 98 ] miR-21 miRNA Tumour-associated macrophages derived sEVs-miR-21 confer cisplatin resistance in GC [ 99 ] anti-miR-214 miRNA Reverse the resistance to cisplatin in GC [ 52 ] miR-522 miRNA Inhibit ferroptosis in cancer cells by targeting ALOX15 and blocking lipid-ROS accumulation [ 100 ] miR-500a-3p miRNA Could be a potential modality for the prediction and treatment of GC with chemoresistance [ 101 ] HOTTIP lncRNA Contribute to cisplatin resistance in GC cells by regulating miR-218/HMGA1 axis [ 102 ] circ-0000260 circRNA Contribute to cisplatin resistance by upregulating MMP11 via targeting miR-129-5p. [ 103 ] circ-PVT1 circRNA Contribute to cisplatin resistance via miR-30a-5p/YAP1 axis. [ 104 ] Oxaliplatin circ-0032821 circRNA Contribute to oxaliplatin resistance by regulating SOX9 via miR-515-5p [ 105 ] 5-FU TFAP2E protein Hypermethylation of TFAP2E resulted in 5-FU chemoresistance in GC cells [ 106 ] Doxorubicin miR-501 miRNA Resistance to doxorubicin is possibly achieved by sEVs-miR-501-induced downregulation of BLID, subsequent inactivation of caspase-9/− 3 and phosphorylation of Akt.…”

Role of Exosomal Non-coding RNAs in Gastric Cancer: Biological Functions and Potential Clinical Applications

“…Other studies have also found that circPVT1 and circ_0000260 are elevated in DDP-resistant GC cells and serum exosomes, and both of these circRNAs achieve DDP resistance through the ceRNA mechanism. Circ-PVT1 and circ_0000260 promote DDP resistance through the miR-30a-5p/YAP1 and miR-129-5p/ MMP11 axes, respectively (89,145). In addition, Zhong et al found that circ_0032821 is highly expressed in oxaliplatin (OXA)-resistant GC cells and their secreted exosomes.…”