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

Abstract

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.

Up-Regulation of circEIF6 Contributes to Pancreatic Cancer Development Through Targeting miR-557/SLC7A11/PI3K/AKT Signaling

“…31 The forced expression of circ_0000520 attenuated the herceptin resistance of gastric cancer cells through suppressing PI3K/AKT signaling. 32 We found that circEIF6 interference also restrained the activity of PI3K/AKT signaling in pancreatic cancer cells. Through performing bioinformatic analysis and dualluciferase reporter assay, miR-557 was verified as a target of circEIF6 in pancreatic cancer cells.…”

The Emerging Roles of Circular RNAs in the Chemoresistance of Gastrointestinal Cancer

“…These results suggested the important role of circDONSON in GC, indicating that it represented a promising therapeutic target for improving chemotherapy effectiveness in GC patients. In contrast, hsa_circ_0000520 was downregulated in Herceptin-resistant GC cells compared with GC cells (Lv et al, 2020). Hsa_circ_0000520 overexpression apparently decreased the viability and promoted the apoptosis of chemoresistant GC cells by upregulating Bax and downregulating Bcl-2.…”

Identification of Circular RNA-Based Immunomodulatory Networks in Colorectal Cancer

“…Controversially, hsa_circ_0000520 has been reported in gastric, breast, and cervical cancers. Sun et al (35) and Lv et al (36) found that hsa_circ_0000520 was significantly downregulated in gastric cancer, and its overexpression may attenuate the PI3K-Akt signalling pathway, causing the reversal of resistance to Herceptin in gastric cancer cells. Zang (37) and Zhou (38) simultaneously reported that hsa_circ_0000520 was highly expressed in breast cancer, which suggested the regulatory mechanism of hsa_circ_0000520/miR-1296.…”