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pmid:35095494
MicroRNA-92a-3p Enhances Cisplatin Resistance by Regulating Krüppel-Like Factor 4-Mediated Cell Apoptosis and Epithelial-to-Mesenchymal Transition in Cervical Cancer.
Jing Yang · Jing Hai · Xuecai Dong · Mengjie Zhang · Shufeng Duan
Frontiers in pharmacology · 2021 doi:10.3389/fphar.2021.783213
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Complete file
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The present study aims to establish a novel role for miR-92a-3p and its associated gene networks in cisplatin (DDP) resistance of CC. First, the disparities in miRNA expression between CC tissues and adjacent normal tissues were screened based on GSE19611 microarray data that retrieved from Gene Expression Omnibus (GEO), and we identified several miRs that were significantly downregulated or upregulated in CC tissues including miR-92a-3p. Moreover, miR-92a-3p was significantly up-regulated in DDP-resistant cells and was the most differently expressed miRNA. Functionally, knockdown of miR-92a-3p increased the sensitivity of DDP-resistant cells to DDP via inhibiting cell proliferation, migration and invasion, and promoting apoptosis. Conversely, overexpression of miR-92a-3p significantly induced DDP resistance in CC parental cells including HeLa and SiHa cells. Moreover, Krüppel-like factor 4 (KLF4) was identified as a direct target of miR-92a-3p, and an obvious inverse correlation was observed between the expression of miR-92a-3p and KLF4 in 40 pairs of cancer tissues. Furthermore, KLF4 knockdown reversed the promoting effect of miR-92a-3p inhibition on DDP sensitivity in DDP-resistant CC cells. Besides, high expression of miR-92a-3p was associated with DDP resistance, as well as a short overall survival in clinic. Taken together, these findings provide important evidence that miR-92a-3p targets KLF4 and is significant in DDP resistance in CC, indicating that miR-92a-3p may be an attractive target to increase DDP sensitivity in clinical CC treatment.", "claims": [{"id": "claim-method", "statement": "Differentially expressed miRNAs (DE-miRNAs) between CC tissue samples and adjacent normal tissues were screened based on GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/), an interactive web tool. 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Conversely, overexpression of miR-92a-3p si", "ls were detected by the Cell Counting Kit-8 (CCK-8) assay (Sigma-Aldrich; Merck KGaA) to determ"], "order_basis": "paper_text_order:51", "id": "assay:1"}, {"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": ["t differently expressed miRNA. Functionally, knockdown of miR-92a-3p increased the sensitivity of D", "0 pairs of cancer tissues. Furthermore, KLF4 knockdown reversed the promoting effect of miR-92a-3p", "ibitor + DDP (10 μM) + si-KLF4 group. During transfection, the cells (2×105 cells/well) were plated in", "d into 6-well culture plates. The cells were transfected using Lipofectamine™ 2000 (Invitrogen; Therm"], "order_basis": "paper_text_order:838", "id": "assay:2"}, {"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": ["DP resistance in CC parental cells including HeLa and SiHa cells. Moreover, Krüppel-like facto", "from ATCC (Manassas, VA, United States) and cultured in DMEM (Dulbecco’s minimum essential medium) c", "ubator with 5% CO2. HeLa and SiHa cells were cultured in increasing concentrations of DDP (Sigma, St.", "nd Treatment Two cervical cancer cell lines (HeLa and SiHa) were purchased from ATCC (Manassas"], "order_basis": "paper_text_order:1111", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Differentially expressed miRNAs (DE-miRNAs) between CC tissue samples and adjacent normal tissues were screened based on GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/), an interactive web tool. The criterion for DE-miRNAs has been set as |fold change| > 1.5 and p < 0.01."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}