circPLIN2 promotes clear cell renal cell carcinoma progression by binding IGF2BP proteins and miR-199a-3p.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36494341", "kind": "science-record", "revision": 4, "content_hash": "sha256:1be9dcac187be17d80b5bf7a5165d5922616de602c8060385e64a35a20a255a5", "created_at": "2026-11-01T19:00:59Z", "updated_at": "2026-11-01T22:50:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "circPLIN2 promotes clear cell renal cell carcinoma progression by binding IGF2BP proteins and miR-199a-3p.", "doi": "10.1038/s41419-022-05488-z", "pmid": "36494341", "authors": ["Bin Zhao", "Cong Huang", "Jie Pan", "Hao Hu", "Xiaojuan Liu", "Kaoyuan Zhang", "Fenli Zhou", "Xin Shi", "Jun Wu", "Bo Yu", "Xiaofan Chen", "Wei Zhang"], "journal": "Cell death & disease", "year": 2022, "abstract": "Recent evidence has indicated that circular RNAs (circRNAs), a novel type of regulatory RNA, play important roles in the development and progression of various cancers. However, the potential regulatory roles and molecular mechanisms of circRNAs in clear cell renal cell carcinoma (ccRCC) remain largely unclear. Here, we explored circRNA expression profiles in 10 paired samples of RCC (including cancer tissues and surrounding tissues) from the Gene Expression Omnibus (GEO) datasets GSE124453 and GSE108735. We initially identified hsa_circ_0086457, designated circPLIN2, derived from exons 4 to 5 of the PLIN2 gene. We observed that circPLIN2 was preferentially located in the cytoplasm and was more stable than its linear counterpart PLIN2. circPLIN2 was significantly upregulated in ccRCC cells and tissues, and its overexpression was correlated with higher clinical stage and worse prognosis for ccRCC patients. Moreover, gain- and loss-of-function assays indicated that circPLIN2 promoted ccRCC cell proliferation, migration, and invasion in vitro and ccRCC tumor growth and metastasis in vivo. Mechanistically, circPLIN2 not only increased the stability of the c-Myc and MARCKSL1 mRNAs by binding to the KH domains of IGF2BP proteins but also competitively sponged miR-199a-3p to abolish the repressive effect of miR-199a-3p on ZEB1 expression, which ultimately resulted in ccRCC tumorigenesis and progression. Collectively, our results suggest that circPLIN2 may represent a promising diagnostic and prognostic biomarker and a potential therapeutic target for ccRCC patients.", "claims": [{"id": "claim-method", "statement": "DESeq2 was used to read the raw count matrix after filtration, and normalization was performed using the variance stabilizing transformation algorithm [58]. Significantly differentially expressed circRNAs between RCC and normal samples were screened with the criteria of adjusted p value less than 0.05 and absolute value of log2(fold change) more than 2.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36494341", "locator": "sections[13] \"Bioinformatics analysis of the circRNA expression profile in RCC\" paragraph 2", "quote": "DESeq2 was used to read the raw count matrix after filtration, and normalization was performed using the variance stabilizing transformation algorithm [58]. Significantly differentially expressed circRNAs between RCC and normal samples were screened with the criteria of adjusted p value less than 0.05 and absolute value of log2(fold change) more than 2."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data underlying this article will be shared on reasonable request to the corresponding author.\nThe computer code used during the current study is available from the corresponding authors on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36494341", "locator": "sections[32] \"Data Availability Statement\" paragraphs 1-3", "quote": "The data underlying this article will be shared on reasonable request to the corresponding author.\nThe computer code used during the current study is available from the corresponding authors on reasonable request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36494341"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Mechanistically, circPLIN2 not only increas"], "order_basis": "paper_text_order:1157", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["idization staining was performed on a tissue microarray of human ccRCC, including 90 cases of tumor", "ining for circPLIN2 expression in the tissue microarray were shown (Fig. 2A). We found that circPLIN", "three pairs of samples from the ccRCC tissue microarray. Scale bar, 20 μm. B circPLIN2 ISH staining"], "order_basis": "paper_text_order:1847", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ell line) to test circPLIN2 expression by RT–qPCR. The results showed that circPLIN2 was obser", "ents with ccRCC are shown on the right. C RT–qPCR analysis of the relative expression levels o"], "order_basis": "paper_text_order:2582", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["DESeq2 was used to read the raw count matrix after filtration, and normalization was performed using the variance stabilizing transformation algorithm [58]. Significantly differentially expressed circRNAs between RCC and normal samples were screened with the criteria of adjusted p value less than 0.05 and absolute value of log2(fold change) more than 2."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}