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pmid:34798882

MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A.

Jin Wang · Lingxia Liu

Journal of ovarian research · 2021 doi:10.1186/s13048-021-00919-5

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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title
MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A.
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10.1186/s13048-021-00919-5
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Jin Wang
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Lingxia Liu
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Journal of ovarian research
year
2021
abstract
BACKGROUND: Ovarian cancer (OC), a kind of gynecological cancer, is characterized by high mortality rate, with microRNAs (miRNAs) playing essential roles in it. However, the clinical significance of miRNAs and their molecular mechanisms in OC are mostly unknown. METHODS: miR-149-3p expression was predicted through Gene Expression Omnibus (GEO) data in OC and confirmed by q-PCR in various OC cells and tissues from patients with different clinical characteristics. Moreover, its roles in terms of proliferation, migration and invasion were measured by CCK-8, colony formation, wound healing and transwell assays in OC cells including cisplatin-resistant and cisplatin-sensitive cells. And its effect on epithelial-mesenchymal transition was also assessed through detecting related protein expression. Additionally, its potential targets were verified by dual luciferase assay and Ago-RIP assay. Finally, its oncogenic functions were explored in vivo. RESULTS: In data from GSE79943, GSE131790, and TCGA, miR-149-3p was found to be highly expressed in OC tissues and associated with poor survival. In metastasis and chemoresistant tissues and cisplatin-resistant OC cells, its high expression was confirmed. In terms of tumorigenic effects, miR-149-3p knockdown in cisplatin-resistant OC cells inhibited its cisplatin resistance and other malignant phenotypes, while miR-149-3p overexpression in cisplatin-resistant OC cells led to contrary results. Mechanistically, miR-149-3p targeted 3'UTR of CDKN1A and TIMP2 to function as an oncogenic miRNA. CONCLUSION: In brief, miR-149-3p promoted cisplatin resistance and EMT in OC by downregulating CDKN1A and TIMP2, which might provide a potential therapeutic target for OC treatment.
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The data of patients with high miR-149-3p expression and low miR-149-3p expression was gathered from the Cancer Genome Atlas (TCGA), and survival probability was assessed by Kaplan Meier which was commonly used to evaluate the influences of various genes on survival.
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The data of patients with high miR-149-3p expression and low miR-149-3p expression was gathered from the Cancer Genome Atlas (TCGA), and survival probability was assessed by Kaplan Meier which was commonly used to evaluate the influences of various genes on survival.
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High expression of miR-149-3p was correlated with poor overall survival, disease specific survival and progress free interval (Fig. 1E).
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ion, migration and invasion were measured by CCK-8, colony formation, wound healing and transwe
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In terms of tumorigenic effects, miR-149-3p knockdown in cisplatin-resistant OC cells inhibited it
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Academy of Sciences (Shanghai, China). These cell lines were cultured in DMEM (Dulbecco’s modified Eagle’s medium)
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Complete file
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However, the clinical significance of miRNAs and their molecular mechanisms in OC are mostly unknown.\nMETHODS: miR-149-3p expression was predicted through Gene Expression Omnibus (GEO) data in OC and confirmed by q-PCR in various OC cells and tissues from patients with different clinical characteristics. Moreover, its roles in terms of proliferation, migration and invasion were measured by CCK-8, colony formation, wound healing and transwell assays in OC cells including cisplatin-resistant and cisplatin-sensitive cells. And its effect on epithelial-mesenchymal transition was also assessed through detecting related protein expression. Additionally, its potential targets were verified by dual luciferase assay and Ago-RIP assay. Finally, its oncogenic functions were explored in vivo.\nRESULTS: In data from GSE79943, GSE131790, and TCGA, miR-149-3p was found to be highly expressed in OC tissues and associated with poor survival. In metastasis and chemoresistant tissues and cisplatin-resistant OC cells, its high expression was confirmed. In terms of tumorigenic effects, miR-149-3p knockdown in cisplatin-resistant OC cells inhibited its cisplatin resistance and other malignant phenotypes, while miR-149-3p overexpression in cisplatin-resistant OC cells led to contrary results. Mechanistically, miR-149-3p targeted 3'UTR of CDKN1A and TIMP2 to function as an oncogenic miRNA.\nCONCLUSION: In brief, miR-149-3p promoted cisplatin resistance and EMT in OC by downregulating CDKN1A and TIMP2, which might provide a potential therapeutic target for OC treatment.", "claims": [{"id": "claim-method", "statement": "The data of patients with high miR-149-3p expression and low miR-149-3p expression was gathered from the Cancer Genome Atlas (TCGA), and survival probability was assessed by Kaplan Meier which was commonly used to evaluate the influences of various genes on survival.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34798882", "locator": "sections[6] \"Prognostic analysis\" paragraph 2", "quote": "The data of patients with high miR-149-3p expression and low miR-149-3p expression was gathered from the Cancer Genome Atlas (TCGA), and survival probability was assessed by Kaplan Meier which was commonly used to evaluate the influences of various genes on survival."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are available from the corresponding author upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34798882", "locator": "sections[31] \"Availability of data and materials\" paragraph 2", "quote": "The data used to support the findings of this study are available from the corresponding author upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "High expression of miR-149-3p was correlated with poor overall survival, disease specific survival and progress free interval (Fig. 1E).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34798882", "locator": "sections[19] \"miR-149-3p is upregulated in OC and associated with poor clinical outcome\" paragraph 2", "quote": "High expression of miR-149-3p was correlated with poor overall survival, disease specific survival and progress free interval (Fig. 1E)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "High expression of miR-149-3p was correlated with poor overall survival, disease specific survival and progress free interval (Fig. 1E).", "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:34798882"], "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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RESULTS: In data from GSE79943, GSE131790,"], "order_basis": "paper_text_order:1011", "id": "assay:2"}, {"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": ["In terms of tumorigenic effects, miR-149-3p knockdown in cisplatin-resistant OC cells inhibited it", "file 2: Supplementary Table 1. Sequences of siRNA and shRNA Against Specific Targets. Suppleme", "upplementary Table 1. Sequences of siRNA and shRNA Against Specific Targets. Supplementary Tabl"], "order_basis": "paper_text_order:1321", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Academy of Sciences (Shanghai, China). These cell lines were cultured in DMEM (Dulbecco’s modified Eagle’s medium)", "ces (Shanghai, China). These cell lines were cultured in DMEM (Dulbecco’s modified Eagle’s medium) su"], "order_basis": "paper_text_order:2657", "id": "assay:4"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["error of the mean (SEM). The photographs of Western blot were analysed by Image J software. 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