ff0599329567f824a22c0a85126339cf pmc_34947804.pdf 810f2a186cc15b6940e1e16bffcb4b9eeb17f4a9 pmc_34947804.pdf b62df0717427cf9bde7afa825b4a316ad6d163d0013d0a72e6e556ba7a889176 pmc_34947804.pdf Title: MicroRNAs as a Suitable Biomarker to Detect the Effects of Long-Term Exposures to Nanomaterials. Studies on TiO2NP and MWCNT Subject: The presence of nanomaterials (NMs) in the environment may represent a serious risk to human health, especially in a scenario of chronic exposure. To evaluate the potential relationship between NM-induced epigenetic alterations and carcinogenesis, the present study analyzed a panel of 33 miRNAs related to the cell transformation process in BEAS-2B cells transformed by TiO2NP and long-term MWCNT exposure. Our battery revealed a large impact on miRNA expression profiling in cells exposed to both NMs. From this analysis, a small set of five miRNAs (miR-23a, miR-25, miR-96, miR-210, and miR-502) were identified as informative biomarkers of the transforming effects induced by NM exposures. The usefulness of this reduced miRNA battery was further validated in other previously generated transformed cell systems by long-term exposure to other NMs (CoNP, ZnONP, MSiNP, and CeO2NP). Interestingly, the five selected miRNAs were consistently overexpressed in all cell lines and NMs tested. These results confirm the suitability of the proposed set of mRNAs to identify the potential transforming ability of NMs. Particular attention should be paid to the epigenome and especially to miRNAs for hazard assessment of NMs, as wells as for the study of the underlying mechanisms of action. Keywords: microRNAs; oncogenesis; carcinogenesis; cell transformation; nanomaterials; long-term exposures; TiO2NP; MWCNT Author: Sandra Ballesteros, Gerard Vales, Antonia Velázquez, Susana Pastor, Mohamed Alaraby, Ricard Marcos and Alba Hernández Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Dec 23 09:25:41 2021 CET ModDate: Thu Dec 23 09:32:21 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3406805 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- AIQCCL+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 15 0 BOKRUM+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 PJURHH+URWPalladioL-Bold Type 1 Custom yes yes no 24 0 PSASYG+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 NPLVPL+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 53 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 57 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 61 0 YFFKLH+CMSY10 Type 1 Builtin yes yes no 76 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 80 0 CAMXTK+EURM10 Type 1 Builtin yes yes no 84 0 ESSRQF+VnURWPalladioL-Italic Type 1 Custom yes yes no 138 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 02:52:35 CEST RepresentationInformation: pmc_34947804.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:06:38 CEST Size: 3406805 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 308 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Nanomaterials Characterization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Cell Culture and Exposure Conditions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: RNA Extraction and Retrotranscription Experiments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Real-Time RT-PCR Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Pathway-Enrichment Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Validation of the Selected Battery of MicroRNAs as Biomarkers of Long-Term Effects of NMs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: MicroRNA Expression Changes after TiO2 NP Exposure Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: MicroRNA Expression Changes after MWCNT Exposure Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Pathway-Enrichment Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Validation of a Set of MicroRNAs as Informative Biomarkers of Long-Term Effects of NMs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Info: Title: MicroRNAs as a Suitable Biomarker to Detect the Effects of Long-Term Exposures to Nanomaterials. Studies on TiO2NP and MWCNT Author: Sandra Ballesteros, Gerard Vales, Antonia Velázquez, Susana Pastor, Mohamed Alaraby, Ricard Marcos and Alba Hernández Subject: The presence of nanomaterials (NMs) in the environment may represent a serious risk to human health, especially in a scenario of chronic exposure. To evaluate the potential relationship between NM-induced epigenetic alterations and carcinogenesis, the present study analyzed a panel of 33 miRNAs related to the cell transformation process in BEAS-2B cells transformed by TiO2NP and long-term MWCNT exposure. Our battery revealed a large impact on miRNA expression profiling in cells exposed to both NMs. From this analysis, a small set of five miRNAs (miR-23a, miR-25, miR-96, miR-210, and miR-502) were identified as informative biomarkers of the transforming effects induced by NM exposures. The usefulness of this reduced miRNA battery was further validated in other previously generated transformed cell systems by long-term exposure to other NMs (CoNP, ZnONP, MSiNP, and CeO2NP). Interestingly, the five selected miRNAs were consistently overexpressed in all cell lines and NMs tested. These results confirm the suitability of the proposed set of mRNAs to identify the potential transforming ability of NMs. Particular attention should be paid to the epigenome and especially to miRNAs for hazard assessment of NMs, as wells as for the study of the underlying mechanisms of action. Keywords: microRNAs; oncogenesis; carcinogenesis; cell transformation; nanomaterials; long-term exposures; TiO2NP; MWCNT Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Dec 23 09:25:41 CET 2021 ModDate: Thu Dec 23 09:32:21 CET 2021 ID: 0x1fa68bd14dd8dee2dd5f89eafbf231d0, 0x1fa68bd14dd8dee2dd5f89eafbf231d0 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: MPUDFL+PazoMath FontSubset: true FirstChar: 68 LastChar: 68 FontDescriptor: FontName: MPUDFL+PazoMath Flags: Symbolic FontBBox: -40, -283, 878, 946 FontFile: true Font: BaseFont: BOKRUM+URWPalladioL-Ital FontSubset: true FirstChar: 44 LastChar: 150 FontDescriptor: FontName: BOKRUM+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: CAMXTK+EURM10 FontSubset: true FirstChar: 12 LastChar: 22 FontDescriptor: FontName: CAMXTK+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: 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