CONSORT: Sam68 Is Directly Regulated by MiR-204 and Promotes the Self-Renewal Potential of Breast Cancer Cells by Activating the Wnt/Beta-Catenin Signaling Pathway.

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The 68 kDa Src-associated protein in mitosis (Sam68) has been linked to the development and progression of breast cancer; however, the posttranscriptional regulation and role of Sam68 in BCSC self-renewal remain unclear.Sam68 was ectopically overexpressed or knocked down using a siRNA; the self-renewal potential of breast cancer cell lines was assessed using flow cytometry, in vitro mammosphere culture and a xenograft model in NOD/SCID mice. Activation of beta-catenin was assessed by immunohistochemical staining, Western blotting, and luciferase reporter gene assays. The ArrayExpress dataset GSE45666 was used to identify conserved microRNAs downregulated in breast cancer; real-time PCR, Western blotting, luciferase reporter assay, and xenografted tumor model were used to confirm miR-204 regulated Sam68.We found that endogenous Sam68 expression correlated positively with the self-renewal potential of breast cancer cell lines. Overexpression of Sam68 promoted, whereas knockdown reduced, breast cancer cell self-renewal potential in vitro and tumorigenicity in vivo. The Wnt/beta-catenin pathway was identified as a functional mediator of Sam68-induced self-renewal in SKBR-3 and MCF-7 cells. Furthermore, miR-204 was found to be frequently downregulated in human breast cancer and confirmed to directly target Sam68; miR-204 inhibited the self-renewal of breast cancer cell lines by targeting and suppressing Sam68.Our study reveals that Sam68 is regulated by miR-204 and may play an important role in the self-renewal of BCSCs via activating the Wnt/beta-catenin pathway. Sam68 may represent a novel therapeutic target for breast cancer.", "claims": [{"id": "claim-method", "statement": "Correlation between the protein level of Sam68 protein and the proportion of SP cells in breast cancer cells by Student t test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26656364", "locator": "sections[14] \"Endogenous Sam68 Expression Positively Correlates With the Self-Renewal Potential of Breast Cancer Cell Lines\" paragraph 3", "quote": "Correlation between the protein level of Sam68 protein and the proportion of SP cells in breast cancer cells by Student t test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Using the ArrayExpress dataset GSE45666, we observed that miR-204 was the only miRNA that was significantly downregulated in 101 breast cancer tissues compared to 15 tumor-adjacent normal breast tissues (Fig. 6A and B).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26656364", "locator": "sections[19] \"MicroRNA-204 Is Frequently Downregulated in Human Breast Cancer and Directly Targets the 3′-UTR of Sam68\" paragraph 2", "quote": "Using the ArrayExpress dataset GSE45666, we observed that miR-204 was the only miRNA that was significantly downregulated in 101 breast cancer tissues compared to 15 tumor-adjacent normal breast tissues (Fig. 6A and B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper used a Student t test for statistical analysis and obtained expression data from the ArrayExpress dataset GSE45666; its headline finding was that miR-204 was the only microRNA significantly downregulated in breast cancer tissues and that miR-204 directly targets the 3′-UTR of Sam68.", "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:26656364"], "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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