Analysis and validation of m6A regulatory network: a novel circBACH2/has-miR-944/HNRNPC axis in breast cancer progression.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34952600", "kind": "science-record", "revision": 3, "content_hash": "sha256:364cc36989791386d0051ba9afebc9cdd4fa60d77af3c0bfe7eeba45b0a6f61c", "created_at": "2026-11-01T17:36:40Z", "updated_at": "2026-11-01T21:26:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis and validation of m6A regulatory network: a novel circBACH2/has-miR-944/HNRNPC axis in breast cancer progression.", "doi": "10.1186/s12967-021-03196-4", "pmid": "34952600", "authors": ["Wenchang Lv", "Yufang Tan", "Mingchen Xiong", "Chongru Zhao", "Yichen Wang", "Min Wu", "Yiping Wu", "Qi Zhang"], "journal": "Journal of translational medicine", "year": 2021, "abstract": "BACKGROUND: N6-methyladenosine (m6A), the most abundant and reversible modification of mRNAs in eukaryotes, plays pivotal role in breast cancer (BC) tumorigenesis and progression. Circular RNAs (circRNAs) can act as tumor promoters or suppressors by microRNA (miRNA) sponges in BC. However, the underlying mechanism of circRNAs in BC progression via regulating m6A modulators remains unclear.\nMETHODS: Prognostic m6A RNA methylation regulators were identified in 1065 BC patients from The Cancer Genome Atlas (TCGA) project. Differentially expressed (DE) miRNAs and DE circRNAs were identified between BC and normal samples in TCGA and GSE101123, respectively. MiRNA-mRNA interactive pairs and circRNA-miRNA interactive pairs were verified by MiRDIP and Circular RNA Interactome. GSEA, KEGG, and ssGSEA were executed to explore the potential biological and immune functions between HNRNPC-high and HNRNPC-low expression groups. qRT-PCR and Western blot were used to quantify the expression of HNRNPC and circBACH2 in MCF-7 and MDA-MB-231 cells. The proliferation of BC cells was assessed by CCK-8 and EdU assay.\nRESULTS: 2 m6A RNA methylation regulators with prognostic value, including HNRNPC and YTHDF3, were identified in BC patients. Then, the regulatory network of circRNA-miRNA-m6A modulators was constructed, which consisted of 2 DE m6A modulators (HNRNPC and YTHDF3), 12 DE miRNAs, and 11 DE circRNAs. Notably, BC patients with high expression of HNRNPC and low expression of hsa-miR-944 were correlated with late clinical stages and shorter survival times. Besides, the results from the KEGG inferred that the DE HNRNPC was associated with the MAPK signaling pathway in BC. Moreover, the circBACH2 (hsa_circ_0001625) was confirmed to act as hsa-miR-944 sponge to stimulate HNRNPC expression to promote BC cell proliferation via MAPK signaling pathway, thus constructing a circBACH2/hsa-miR-944/HNRNPC axis in BC.\nCONCLUSIONS: Our findings decipher a novel circRNA-based m6A regulatory mechanism involved in BC progression, thus providing attractive diagnostic and therapeutic strategies for combating BC.", "claims": [{"id": "claim-method", "statement": "The prognostic value of the m6A RNA methylation modulators was further assessed by univariate Cox regression survival analyses and Lasso Cox regression analysis, and those DE modulators were identified as components of the following network construction.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34952600", "locator": "sections[4] \"Identification of DE genes\" paragraph 2", "quote": "The prognostic value of the m6A RNA methylation modulators was further assessed by univariate Cox regression survival analyses and Lasso Cox regression analysis, and those DE modulators were identified as components of the following network construction."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study could be found in online database. The original contributions presented in the study are deposited in the article and Supplementary Material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34952600", "locator": "sections[28] \"Availability of data and materials\" paragraph 2", "quote": "The datasets presented in this study could be found in online database. The original contributions presented in the study are deposited in the article and Supplementary Material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "2 m6A RNA methylation regulators with prognostic value, including HNRNPC and YTHDF3, were identified in BC patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34952600", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "2 m6A RNA methylation regulators with prognostic value, including HNRNPC and YTHDF3, were identified in BC patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "2 m6A RNA methylation regulators with prognostic value, including HNRNPC and YTHDF3, were identified in BC patients.", "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:34952600"], "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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The proliferation of B", "e Culture Collection (Manassas, VA, USA) and cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) su", "re and transfection The human BC cell lines, MCF-7 and MDA-MB-231 were obtained from American T", "he CCK8 assay indicated the proliferation of MCF-7 cells (A) and MDA-MB-231 cells (B) after tra"], "order_basis": "paper_text_order:1095", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["he proliferation of BC cells was assessed by CCK-8 and EdU assay. RESULTS: 2 m6A RNA methylatio", "ls of hsa-miR-944 and HNRNPC. Figure S6. The CCK8 assay indicated the proliferation of MCF-7 c"], "order_basis": "paper_text_order:1169", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["of immune-related pathways. Cell culture and transfection The human BC cell lines, MCF-7 and MDA-MB-23", "han, China). The cells in 6 well plates were transfected with 50 nM inhibitors or siRNA by using Lipo", "ependent experiments were performed for cell transfection. Statistical analysis All statistical analys", "F-7 cells (A) and MDA-MB-231 cells (B) after transfection with HNRNPC siRNAs or negative control. Tabl"], "order_basis": "paper_text_order:3452", "id": "assay:4"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The prognostic value of the m6A RNA methylation modulators was further assessed by univariate Cox regression survival analyses and Lasso Cox regression analysis, and those DE modulators were identified as components of the following network construction."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}