hsa_circ_0000520 influences herceptin resistance in gastric cancer cells through PI3K-Akt signaling pathway.

BACKGROUND: To investigate whether hsa_circ_0000520 affects Herceptin resistance in gastric cancer by regulating the PI3K-AKT signaling. METHODS: The expression of hsa_circ_0000520 was detected by qRT-PCR in gastric cancer tissues and cell lines. A Herceptin-resistant gastric cancer cell was established. PcDNA and pcDNA-hsa_circ_0000520 were transfected into NCI-N87R cells and treated with Herceptin at a concentration of 10 µg/mL for 24 hours. MTT tested cell proliferation, and apoptosis was measured by flow cytometry. IGF-1 treatment was used to activate PI3K-Akt signaling. The expression levels of related proteins were detected. RESULTS: The expression of hsa_circ_0000520 was reduced in gastric cancer tissues and cell lines, and hsa_circ_0000520 in NCI-N87R cells was significantly lower than that of NCI-N87 cells. Compared with the CON group, the cell viability of the Herceptin group was significantly reduced, the apoptosis rate was significantly increased, the level of Bax protein was significantly increased, and the levels of Bcl-2, p-PI3K, and p-Akt protein were significantly reduced. Compared with the Herceptin + pcDNA group, the cell viability of the Herceptin + hsa_circ_0000520 group was significantly reduced, the apoptosis rate was significantly increased, the level of Bax protein was significantly increased, and the levels of p-PI3K and p-Akt proteins were significantly reduced. After IGF-1 treatment, the cell viability was significantly increased, the apoptosis rate was significantly reduced, the level of Bax protein was significantly reduced, and the level of Bcl-2 protein was significantly increased. CONCLUSION: Hsa_circ_0000520 overexpression may reverse the Herceptin resistance of gastric cancer cells by inhibiting the PI3K-Akt signaling pathway.

Long non-coding RNA-ZNF281 promotes cancer cell migration and invasion in gastric cancer via downregulation of microRNA-124.

It has previously been determined that long non-coding (lnc)RNA-zinc finger protein (ZNF)281 serves an oncogenic role in breast cancer; however, the role of lncRNA-ZNF281 in other cancer types is yet to be elucidated. The present study aimed to analyze the role of ZNF281 in gastric cancer by characterizing its activity in cancerous tissues and normal tissues using RT-qPCR. Overexpression experiments were also performed to investigate the interaction between ZNF281 and miR-124, and Transwell assays were conducted to analyze cell invasion and migration. The present study revealed that lncRNA-ZNF281 was upregulated, and that microRNA (miR)-124 was downregulated, in cancerous tissues compared with that in the paired adjacent healthy tissues of patients with gastric cancer. In addition, the expression levels of lncRNA-ZNF281 and miR-124 exhibited a significant inverse association. Furthermore, in vitro cell experiments determined that lncRNA-ZNF281 overexpression resulted in miR-124 inhibition, yet miR-124 overexpression did not influence lncRNA-ZNF281 expression. lncRNA-ZNF281 expression level was also associated with the clinical stage of the patient. Bioinformatics analysis revealed that lncRNA-ZNF281 may target the base pairs in the hairpin loop of the miR-124 precursor. Subsequent in vitro cell experiments indicated that lncRNA-ZNF281 overexpression resulted in promoting the migration and invasiveness of gastric cancer cells, while miR-124 over-expression led to its inhibition. In addition, miR-124 overexpression partially recovered the effects of lncRNA-ZNF281 overexpression. Therefore, lncRNA-ZNF281 may promote cancer cell migration and invasion in gastric cancer via downregulation of miR-124.