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pmid:35611198
Identification of circ_0000375 and circ_0011536 as novel diagnostic biomarkers of colorectal cancer.
Teng-Fei Yin · Shi-Yu Du · Dong-Yan Zhao · Xi-Zhen Sun · Yuan-Chen Zhou · Qian-Qian Wang · Ge-Yu-Jia Zhou · Shu-Kun Yao
World journal of clinical cases · 2022 doi:10.12998/wjcc.v10.i11.3352
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Experiment
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Data
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Analysis
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Complete file
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Circular ribonucleic acids (circRNAs), a new type of noncoding RNA, are considered to participate in cancer pathogenesis as microRNA (miRNA) sponges. However, the dysregulation and biological functions of circRNAs in CRC remain to be explored.\nAIM: To identify potential circRNA biomarkers of CRC and explore their functions in CRC carcinogenesis.\nMETHODS: CircRNAs and miRNAs differentially expressed in CRC tissues were identified by analyzing expression profiles from the Gene Expression Omnibus (GEO) database. Circ_0000375 and circ_0011536 were selected as CRC biomarker candidates. Quantitative real-time polymerase chain reaction was utilized to evaluate the expression of these 2 circRNAs in CRC tissues, serums and cell lines. Receiver operating characteristic curves were generated to assess the diagnostic performances of these 2 circRNAs. Then, functional experiments, including cell counting kit-8, wound healing and Transwell invasion assays, were performed after the overexpression of circ_0000375 and circ_0011536 in CRC cell lines. Furthermore, candidate target miRNAs of circ_0000375 and circ_0011536 were predicted via bioinformatics analysis. The expression levels of these miRNAs were explored in CRC cell lines and tissues from GEO datasets. A luciferase reporter assay was developed to examine the interactions between circRNAs and miRNAs. Based on the target miRNAs and downstream genes, functional enrichment analyses were applied to reveal the critical signaling pathways involved in CRC carcinogenesis.\nRESULTS: Downregulated circ_0000375 and circ_0011536 expression was observed in CRC tissues in GSE126095, clinical CRC tissue and serum samples and CRC cell lines. The areas under the curve for circ_0000375 and circ_0011536 were 0.911 and 0.885 in CRC tissue and 0.976 and 0.982 in CRC serum, respectively. Moreover, the serum levels of these 2 circRNAs were higher in patients at 30 d postsurgery than in patients before surgery, suggesting that the serum expression of circ_0000375 and circ_0011536 is related to CRC tumorigenesis. Circ_0000375 and circ_0011536 overexpression inhibited the proliferation, migration and invasion of CRC cells. Furthermore, miR-1182 and miR-1246, which were overexpressed in CRC tissues in GSE41655, GSE49246 and GSE115513, were verified as target miRNAs of circ_0000375 and circ_0011536, respectively, by luciferase reporter assays. The downstream genes of miR-1182 and miR-1246 were enriched in some CRC-associated pathways, such as the Wnt signaling pathway.\nCONCLUSION: Circ_0000375 and circ_0011536 may function as tumor suppressors in CRC progression, serving as novel biomarkers for CRC diagnosis and as promising candidates for therapeutic exploration.", "claims": [{"id": "claim-method", "statement": "The “limma” R package was used for normalization of raw data and identification of the differentially expressed circRNAs and miRNAs between CRC and NC samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35611198", "locator": "sections[4] \"Bioinformatic analysis of circRNA and miRNA profiles\" paragraph 2", "quote": "The “limma” R package was used for normalization of raw data and identification of the differentially expressed circRNAs and miRNAs between CRC and NC samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "No additional data are available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35611198", "locator": "sections[34] \"Footnotes\" paragraph 2", "quote": "No additional data are available."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper identified differentially expressed circRNAs and miRNAs in CRC tissues by analyzing expression profiles from the Gene Expression Omnibus (GEO) database.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35611198", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "CircRNAs and miRNAs differentially expressed in CRC tissues were identified by analyzing expression profiles from the Gene Expression Omnibus (GEO) database."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The paper identified differentially expressed circRNAs and miRNAs in CRC tissues by analyzing expression profiles from the Gene Expression Omnibus (GEO) database.", "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:35611198"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE115513"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE115513"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35611198", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.12998/wjcc.v10.i11.3352", "sha256": 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"GSM3181333", "GSM3181334", "GSM3181335", "GSM3181336", "GSM3181337", "GSM3181338", "GSM3181339", "GSM3181340", "GSM3181341", "GSM3181342", "GSM3181343", "GSM3181344", "GSM3181345", "GSM3181346", "GSM3181347", "GSM3181348", "GSM3181349", "GSM3181350", "GSM3181351", "GSM3181352", "GSM3181353", "GSM3181354", "GSM3181355", "GSM3181356", "GSM3181357", "GSM3181358", "GSM3181359", "GSM3181360", "GSM3181361", "GSM3181362", "GSM3181363", "GSM3181364"], "sample_count": 1513, "group_sizes": null, "group_sizes_basis": null, "platform": "18402", "taxon": "Homo sapiens", "title": "miRNA and colorectal cancer: associations with tumor phenotype and survival", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE126095", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": 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