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Supplementary Table S1-S8 from CircPDIA4 Induces Gastric Cancer Progression by Promoting ERK1/2 Activation and Enhancing Biogenesis of Oncogenic circRNAs

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posted on 2023-03-31, 06:03 authored by Yue Shen, Nasha Zhang, Jie Chai, Teng Wang, Chi Ma, Linyu Han, Ming Yang

Table S1 shows primers for RT-qPCR. Table S2 shows sequences of shRNAs and siRNAs. Table S3 shows antibodies used in the study. Table S4 shows the sequence of the biotin-labeled probes for circPDIA4 and controls. Table S5 shows the overlap circRNAs of the three gastric cancer cell lines. Table S6 shows the relevant clinic-pathological characteristics of gastric cancer cases stratified by circPDIA4 levels in Combined cohort. Table S7 shows the relevant clinic-pathological characteristics of gastric cancer cases stratified by QKI levels in Combined cohort. Table S8 shows Mass Spectrometry of proteins pulled-down by circPDIA4 in HGC-27 cells.

Funding

Natural Science Foundation of Shandong Province (Natural Science Foundation of Shandong)

Major Scientific and Technological Innovation Project of Shandong Province (山东省重大科技创新工程项目)

Taishan Scholar Foundation of Shandong Province (山东省泰山学者特聘教授)

Science and Technology Support Plan for Youth Innovation of Colleges and Universities of Shandong Province of China (山东省高等学校青年创新团队发展计划)

National Natural Science Foundation of China (NSFC)

History

ARTICLE ABSTRACT

Circular RNAs (circRNA) are a group of noncoding, covalently uninterrupted loop transcripts, most of which remain to be functionally characterized. Here, we identified circPDIA4 as an oncogenic circRNA in gastric cancer. Clinically, circPDIA4 was significantly upregulated in malignant tissues and was associated with poor survival of patients with gastric cancer. The biogenesis of circPDIA4 was mediated by the RNA-binding protein Quaking, which bound introns 2 and 4 of PDIA4 pre-mRNA to promote backsplicing of exons 3 and 4. Elevated expression of circPDIA4 promoted distant metastasis in various mouse xenograft models in vivo and accelerated cancer cell invasion in vitro. CircPDIA4 functioned through distinct oncogenic mechanisms in the cytoplasm and the nucleus. Cytoplasmic circPDIA4 bound to ERK1/2 and sustained hyperactivation of the MAPK pathway by preventing DUSP6-mediated ERK1/2 dephosphorylation. Notably, circPDIA4 depletion enhanced the sensitivity of gastric cancer cells to ERK inhibitors. In the nucleus, circPDIA4 interacted with DHX9 as a decoy and repressed its inhibitory functions on circRNA biogenesis to boost expression of multiple oncogenic circRNAs, which promoted gastric cancer progression. These findings reveal a dual tumor-promoting mechanism for circPDIA4 by regulating oncogenic circRNA biogenesis and increasing MAPK activity. CircPDIA4 should be investigated further as a potential prognostic biomarker and therapeutic target in gastric cancer. Quaking-regulated circPDIA4 mediates different mechanisms in the nucleus and cytoplasm that coordinate to promote progression and drug resistance in gastric cancer.

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