Silencing of circRACGAP1 sensitizes gastric cancer cells to apatinib via modulating autophagy by targeting miR-3657 and ATG7

Ma, Ling; Wang, Zhangding; Xie, Mengyan; Quan, Yunlin; Zhu, Weiyou; Yang, Fengming; Zhao, Cheng; Fan, Yu; Fang, Na; Jiang, Huning; Wang, Qiang; Wang, Shouyu; Zhou, Jianwei; Chen, Xiaofeng; Shu, Yongqian

doi:10.1038/s41419-020-2352-0

Cited by 45 publications

(35 citation statements)

References 58 publications

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“…A through inhibition of miR-198 and up-regulation PIK3R1. Ma, et al 23 revealed that circRACGAP1 enhances resistance to apatinib in GC cells through modulation of autophagy via regulating a miR-3657/ATG7 pathway. Furthermore, research has revealed that circPRRX1 expedites the development of esophageal cancer by binding to miR-1294 and up-regulating LASP1.…”

Section: Discussionmentioning

confidence: 99%

Exosomal CircPRRX1 Enhances Doxorubicin Resistance in Gastric Cancer by Regulating MiR-3064-5p/PTPN14 Signaling

et al. 2020

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Purpose Gastric cancer (GC) is a malignant tumor with a high mortality rate. Drug resistance is a major obstacle to GC therapy. This study aimed to investigate the role and mechanism of exosomal circPRRX1 in doxorubicin resistance in GC. Materials and Methods HGC-27 and AGS cells were exposed to different doses of doxorubicin to construct doxorubicin-resistant cell lines. Levels of circPRRX1, miR-3064-5p, and nonreceptor tyrosine phosphatase 14 (PTPN14) were detected by quantitative real-time PCR or Western blot assay. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, transwell, and Western blot assays were used to explore the function of circPRRX1 in GC cells. Interactions among circPRRX1, miR-3064-5p, and PTPN14 were confirmed by dual-luciferase reporter assay. The in vivo function of circPRRX1 was analyzed in a xenograft tumor model. Results CircPRRX1 was highly expressed in doxorubicin-resistant GC cell lines. Knockdown of circPRRX1 reversed doxorubicin resistance in doxorubicin-resistant GC cells. Additionally, extracellular circPRRX1 was carried by exosomes to spread doxorubicin resistance. CircPRRX1 silencing reduced doxorubicin resistance by targeting miR-3064-5p or regulating PTPN14. In GC patients, high levels of circPRRX1 in serum exosomes were associated with poor responses to doxorubicin treatment. Moreover, depletion of circPRRX1 reduced doxorubicin resistance in vivo. Conclusion CircPRRX1 strengthened doxorubicin resistance by modulating miR-3064-5p/PTPN14 signaling and might be a therapeutic target for GC patients.

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Section: Discussionmentioning

confidence: 99%

Exosomal CircPRRX1 Enhances Doxorubicin Resistance in Gastric Cancer by Regulating MiR-3064-5p/PTPN14 Signaling

et al. 2020

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“…As circRNA has the characteristics of stability and tissue specificity, thus it may become a tumor marker and be involved in progression of gastric cancer. Present study shows that Circ_0032821 promotes gastric cancer development by activating the MEK1/ ERK1/ 2; CircMRPS35 inhibits the progression of gastric cancer; Silencing RACRACGAP1 can enhance the sensitivity to Apatinib by targeting miR‐3657; CircRNA_0005075 inhibits gastric cancer growth via miR‐431/ p53/ epithelial stromal transformation axis; circ_0006282 promotes gastric cancer growth through miR‐155/ FBXO22 axis 11‐15 …”

Section: Discussionmentioning

confidence: 72%

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

Wang

et al. 2020

Clinical Laboratory Analysis

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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.

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“…CDDP, MTA, PTX, and oxaliplatin (OXA) are commonly used in gastric cancer (GC) chemotherapy [ 136 – 138 ]. However, patients always acquire chemotherapeutic resistance after treatment, which limits the overall clinical efficacy of the treatment.…”

Section: Mechanisms Of Circrnas In Drug Resistancementioning

confidence: 99%

“…Zhang et al found that circCCDC66 is an important regulator of CDDP resistance and is highly expressed in CDDP-resistant cells and tissues. In vitro and in vivo experiments showed that circCCDC66 inhibits apoptosis and promotes drug resistance by targeting miR-618 and releasing B cell lymphoma-2 (BCL2) [ 136 ]. Via microarray analysis, Xu et al identified the upregulation of circMTHFD2, which bound directly to miR-124 as a molecular sponge, in GC cells.…”

Section: Mechanisms Of Circrnas In Drug Resistancementioning

confidence: 99%

CircRNAs: biogenesis, functions, and role in drug-resistant Tumours

Kong

et al. 2020

Mol Cancer

107

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Targeted treatment, which can specifically kill tumour cells without affecting normal cells, is a new approach for tumour therapy. However, tumour cells tend to acquire resistance to targeted drugs during treatment. Circular RNAs (circRNAs) are single-stranded RNA molecules with unique structures and important functions. With the development of RNA sequencing technology, circRNAs have been found to be widespread in tumour-resistant cells and to play important regulatory roles. In this review, we present the latest advances in circRNA research and summarize the various mechanisms underlying their regulation. Moreover, we review the role of circRNAs in the chemotherapeutic resistance of tumours and explore the clinical value of circRNA regulation in treating tumour resistance.

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Silencing of circRACGAP1 sensitizes gastric cancer cells to apatinib via modulating autophagy by targeting miR-3657 and ATG7

Cited by 45 publications

References 58 publications

Exosomal CircPRRX1 Enhances Doxorubicin Resistance in Gastric Cancer by Regulating MiR-3064-5p/PTPN14 Signaling

Exosomal CircPRRX1 Enhances Doxorubicin Resistance in Gastric Cancer by Regulating MiR-3064-5p/PTPN14 Signaling

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

CircRNAs: biogenesis, functions, and role in drug-resistant Tumours

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