Circular RNA circPGD contributes to gastric cancer progression via the sponging miR-16-5p/ABL2 axis and encodes a novel PGD-219aa protein

Liu, Yun; Cao, Jia; Zhu, Linqi; Zhao, Wenjun; Zhou, Yong; Shao, Chen; Shao, Shihe

doi:10.1038/s41420-022-01177-0

Cited by 13 publications

(11 citation statements)

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“…al showed that circUBA1 advances the development and metastasis of gastric tumor cells by sponging miR-375 [ 45 ]. Previous researchers have discovered that both hsa_circ0000885 and circPGD can promote cancer progression via sponging miR-16-5p [ 46 , 47 ]. Consistently, in our study, we found that circRANGAP1 promotes HCC progression by sponging miR-27b-3p.…”

Section: Discussionmentioning

confidence: 99%

circRanGAP1/miR-27b-3p/NRAS Axis may promote the progression of hepatocellular Carcinoma

et al. 2022

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Background Though circular RNAs (circRNAs) are the key regulators in tumor carcinogenesis, they remain largely unexplored in hepatocellular carcinoma (HCC). Methods The expression of RanGAP1-derived circRNAs (circ_0063531, circ_0063534, circ_0063513, circ_0063518, circ_0063507, circ_0063723) were evaluated in eight paired HCC and normal tissues, and the correlation between circRanGAP1 (circ_0063531) expression and clinicopathological characteristics in 40 HCC patients was determined. The association between miR-27b-3p and circRanGAP1 or NRAS was predicted using bioinformatics analysis. The expression of circRanGAP1, miR-27b-3p, and NRAS were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The potential oncogenic role of circ-RanGAP1 was assessed using CCK-8, colony formation, transwell assays in vitro, subcutaneous tumor mouse model, vein tail metastatic model, and orthotopically implanted intrahepatic HCC model in vivo. Luciferase reporter and RNA immunoprecipitation (RIP) assays were used to explore the binding site between miR-27b-3p and circ-RanGAP1 or NRAS. Protein expression was detected using western blotting. The localization of miR-27b-3p and circ-RanGAP1 was investigated using fluorescence in situ hybridization (FISH). The level of immune infiltration was assessed by bioinformatics analysis, flow cytometry, and orthotopically implanted intrahepatic HCC models. Results Here, we found elevated circRanGAP1 in the cells and clinical tissues of patients with HCC. Increased circRanGAP1 levels are associated with enlarged tumors and the advanced stage of TNM. CircRanGAP1 promotes the growth, migration, and HCC cell invasion, concurrently with the growth and metastasis of tumors in-vivo. Moreover, circRanGAP1 is mainly located inside the cytoplasm. Mechanistically, circRanGAP1 as an oncogene promotes HCC progression by miR-27b-3p/NRAS/ERK axis, furthermore, affects the infiltration level of tumor-associated macrophages probably by sponging miR-27b-3p. Immune infiltration analysis shows that NRAS is positively correlated with the levels of CD68+ tumor-associated macrophages in HCC samples and that NRAS and CD68 are related to the poor outcome of HCC. Conclusion These results reveal that circRanGAP1 is a HCC oncogene that function by the miR-27b-3p/NRAS/ERK axis and regulates the infiltration levels of tumor-associated macrophages by sponging miR-27b-3p. Therefore, circRANGAP1/ NRAS axis may be an important potential treatment target against HCC.

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Section: Discussionmentioning

confidence: 99%

circRanGAP1/miR-27b-3p/NRAS Axis may promote the progression of hepatocellular Carcinoma

et al. 2022

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“…66 In contrast, Liu's team found that high expression of circPGD in gastric cancer tissues promoted EMT and inhibited the apoptosis of gastric cancer cells. Moreover, circPGD has been shown to exert biological effects not only by sponging miR-16-5p but also by encoding a novel protein, PGD-219aa, which promotes gastric cancer progression by acting on the SMAD2/3 and YAP signalling pathways 67 (Figure 3C).…”

Section: Circrna-encoded Proteins Regulate Tumour Cell Metastasis By ...mentioning

confidence: 99%

Newly discovered mechanisms that mediate tumorigenesis and tumour progression: circRNA‐encoded proteins

Wang

Cao

et al. 2023

J Cellular Molecular Medi

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“…This study was approved by the Medical Ethics Committee of Jiangsu University, and all participants signed an informed consent form. HGC-27 were cultured according to the methods described in a previous article [22] .…”

Section: Patients and Specimensmentioning

confidence: 99%

CircRNA_15430 reduced by Helicobacter pylori infection and suppressed gastric cancer progression via miR-382-5p/ZCCHC14 axis

Liu

Cao

Yang

et al. 2023

Preprint

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Background Helicobacter pylori (H.pylori, HP) is one of the main causes of gastric cancer (GC). CircRNAs have been reported to play a crucial role in developing many types of cancer. However, the role of circRNAs in the development and progression of HP infected-GC has not been studied.Methods Nuclear and cytoplasmic RNA fractionation and RNA fluorescence in situ hybridization analysis (FISH) assays detected the location of circRNA_15430 in GC cells, and quantitative real-time polymerase chain reaction (qRT-PCR) analyzed circRNA_15430, miR-382-5p and ZCCHC14 expression in GC cell lines and tissues. Colony formation, cell counting kit-8 (CCK-8) and Transwell assays, flow cytometry and laser scanning confocal microscopy examined the function of circRNA_15430 in GC cells. Western blotting detected the protein levels. A dual-luciferase reporter assay monitored whether circRNA_15430 sponges miR-382-5p. Furthermore, circRNA_15430 was analyzed in vivo in tumor growth with nude mice.Results CircRNA_15430 is primarily localized in the cytoplasm of GC cells, and downregulated in the GC cell lines and tissues, and is negatively correlated with the tumor size. Downregulation of circRNA_15430 promotes proliferation, migration and suppresses cell apoptosis and autophagy in GC cells. Mechanically, circRNA_15430 acts as a miR-382-5p sponge, alleviating the inhibitory effect of miR-382-5p on its target ZCCHC14. Knockdown circRNA_15430 enhances tumor growth in vivo. In addition, circRNA_15430 was reduced in HP + gastritis tissues and HP-infected MGC-803 cells, reversing the pro-HP effect on autophagy. Additionally, miR-382-5p was increased in HP + gastritis tissue and HP-infected MGC-803 cells while ZCCHC14 decreased in HP-infected MGC-803 cells. MiR-382-5p reverses the effect of si-ZCCHC14 on autophagosome numbers in MGC-803 cells.Conclusions Therefore, circRNA_15430 plays an inhibitory role in GC and regulates the progression of HP infection-related GC, providing a novel molecular marker for GC therapy.

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Circular RNA circPGD contributes to gastric cancer progression via the sponging miR-16-5p/ABL2 axis and encodes a novel PGD-219aa protein

Cited by 13 publications

References 40 publications

circRanGAP1/miR-27b-3p/NRAS Axis may promote the progression of hepatocellular Carcinoma

circRanGAP1/miR-27b-3p/NRAS Axis may promote the progression of hepatocellular Carcinoma

Newly discovered mechanisms that mediate tumorigenesis and tumour progression: circRNA‐encoded proteins

CircRNA_15430 reduced by Helicobacter pylori infection and suppressed gastric cancer progression via miR-382-5p/ZCCHC14 axis

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