MELK is Upregulated in Advanced Clear Cell Renal Cell Carcinoma and Promotes Disease Progression by Phosphorylating PRAS40.

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In this study, in order to screen differentially expressed genes (DEGs) between stage IV and stage I ccRCC specimens, we initially analyzed The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GSE73731). We found that maternal and embryonic leucine zipper kinase (MELK) is upregulated in stage IV ccRCC samples and that upregulation of MELK is significantly correlated with advanced disease status. Furthermore, both loss and gain-of-function assays strengthen the evidence that MELK enforces the malignant phenotype of ccRCC cells through over-activating the mammalian target of rapamycin complex 1 (mTORC1) pathway. Mechanistically, we verified that the oncogenic effect of MELK occurs through phosphorylating PRAS40, an inhibitory subunit of mTORC1, and through disrupting the interaction between PRAS40 and raptor. In summary, these results elucidate the important role of MELK in the progression of ccRCC and indicate that MELK may be a novel regulator of ccRCC progression by over-activating the mTORC1.", "claims": [{"id": "claim-method", "statement": "To screen DEGs, the linear models for microarray data (Limma) package from Bioconductor11 were adopted to compare stage I and stage IV ccRCC samples from TCGA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31813279", "locator": "sections[4] \"Data Pre-processing and DEGs Screening\" paragraph 2", "quote": "To screen DEGs, the linear models for microarray data (Limma) package from Bioconductor11 were adopted to compare stage I and stage IV ccRCC samples from TCGA."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:31813279"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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Cell Culture and Transfection The cell lines ACHN and 769-P were obtained", "with 10% FBS, at 37°C and 5% CO2. Cells were transfected with lipofectamine 3000 (Invitrogen, Carlsba", "(Invitrogen, Carlsbad, CA, USA) for plasmid transfection. MELK plasmid and control vector were transf", "ection. MELK plasmid and control vector were transfected into 769-P and screened with G418 (700 mg/ml"], "order_basis": "paper_text_order:1867", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ection (ATCC, Manassas, VA, USA). 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