Transcriptome Analysis of Caco-2 Cells upon the Exposure of Mycotoxin Deoxynivalenol and Its Acetylated Derivatives
Abstract
:1. Introduction
2. Results
2.1. 3-ADON Exerts Less Harmful Effects Than DON and 15-ADON on Cultured Caco-2 Cells
2.2. Transcriptomic Changes of Caco-2 Cells
2.3. Function Enrichment Analysis of Differentially Expressed Genes (DEGs)
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Cell Culture and Treatment
4.3. Cell Viability Assay
4.4. RNA Extraction
4.5. RNA-seq Analysis
4.6. Real-Time PCR (RT-PCR) Assay
4.7. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Exposure Time (h) | IC50 (µM) ± SD | ||
---|---|---|---|
DON | 3-ADON | 15-ADON | |
24 | 6.17 ± 0.93 | 13.19 ± 0.71 | 3.86 ± 0.31 |
48 | 3.86 ± 2.21 | 10.81 ± 3.84 | 2.33 ± 0.36 |
72 | 1.46 ± 0.42 | 7.84 ± 2.01 | 1.44 ± 0.67 |
Toxin | Top 5 Pathways | Downregulated Genes | Upregulated Genes | p-Value | Count |
---|---|---|---|---|---|
3-ADON | DNA replication | PCNA, MCM4, MCM3, MCM5, MCM6, MCM7, MCM2, POLD1, RFC3, FEN1, POLE2, RFC4, RPA3, RNASEH2A, POLE3, LIG1, POLD3, PRIM1, POLA2, POLD2, RPA1, RFC5, POLE, RNASEH1, RFC2, POLA1, RNASEH2C | − | 1.06 × 10−16 | 27 |
Cell cycle | PCNA, MCM4, E2F1, MCM3, MCM5, CDC6, MCM6, MAD2L1, MCM7, MCM2, CDK1, CCNB1, PTTG1, E2F2, ORC6, CHEK2, CCNA2, CCND1, YWHAB, CDC45, PKMYT1, E2F3, ORC1, CDC25A, CCNE1, CDK2, CDKN2C, ESPL1, TFDP1, CHEK1, BUB1, DBF4, PLK1, RBX1, BUB1B, CDKN2A, CDC25C, MAD2L2, CDC7, CCNE2, SMC1B, CCND3, CDKN2D, CCND2 | WEE2, STAG1, STAG2, ATM | 2.74 × 10−12 | 48 | |
Base excision repair | PCNA, PARP1, POLD1, FEN1, POLE2, POLE3, UNG, LIG1, POLD3, NEIL3, NTHL1, POLE, PARP2, NEIL2, HMGB1, POLD2 | NEIL1, PARP4 | 3.53 × 10−8 | 18 | |
Fanconi anemia pathway | RMI2, UBE2T, RAD51, CENPX, RPA3, EME1, RPA1, TELO2, FANCI, FANCA, FANCG, FANCD2, BRCA1, FANCM, BLM, FANCB, FAAP24, RAD51C, CENPS, CENPS-CORT, ATRIP | EME2, POLK, POLI | 3.58 × 10−8 | 24 | |
Homologous recombination | POLD1, RAD51, RPA3, RAD54L, EME1, POLD3, RPA1, POLD2, XRCC2, BRCA1, RAD54B, XRCC3, RBBP8, BLM, BARD1, RAD51C | ATM, ABRAXAS1 | 2.31 × 10−6 | 18 | |
DON | DNA replication | PCNA, MCM4, MCM3, MCM5, MCM6, MCM2, MCM7, POLD1, POLD2, RFC3, POLE2, RFC4, FEN1, RPA3, RNASEH1, POLE3, LIG1, POLD3, RNASEH2A, PRIM1, POLA2, RFC2, RNASEH2C | − | 1.17 × 10−13 | 23 |
Base excision repair | PCNA, PARP1, POLD1, UNG, POLD2, POLE2, FEN1, POLE3, LIG1, POLD3, NEIL2, HMGB1, NTHL1 | PARP4, NEIL1 | 1.10 × 10−6 | 15 | |
Cell cycle | PCNA, E2F1, MCM4, MCM3, MCM5, E2F2, MCM6, MCM2, MCM7, CCND1, CDK2, MAD2L1, CDC6, ORC6, CCNE1, CDKN2C, TFDP1, CHEK2, CDC45, E2F3, ESPL1, PKMYT1, CDC25A, ORC1, CCND3, CDKN2A, MAD2L2, CDKN2B, CCND2 | WEE2, STAG1, STAG2, ATM | 2.69 × 10−6 | 33 | |
Steroid hormone biosynthesis | CYP1A1, UGT1A6, HSD17B8, HSD11B2, UGT1A4, UGT1A1 | UGT2A3, UGT2B15, UGT2B17, AKR1C2, UGT2B7, UGT2B11, STS, AKR1C1, AKR1C3, CYP17A1, CYP3A5, SULT1E1, UGT2B10, AKR1D1 | 9.00 × 10−6 | 20 | |
Drug metabolism—other enzymes | TK1, NME1, NME4, DUT, NME2, HPRT1, IMPDH1, UCK2, UGT1A6, UPP1, TK2, MGST1, UGT1A4, CDA, UGT1A1 | UGT2A3, GSTA2, UGT2B15, UGT2B17, UGT2B7, UGT2B11, GSTA1, UGT2B10 | 1.81 × 10−5 | 23 | |
15-ADON | DNA replication | PCNA, MCM3, MCM4, MCM5, POLD1, MCM6, MCM2, MCM7, POLE2, POLD2, RFC4, RFC3, RPA3, LIG1, POLE3, RNASEH1, PRIM1, POLD3, POLA2, RFC2 | − | 1.54 × 10−11 | 20 |
Cell cycle | PCNA, MCM3, E2F1, MCM4, MCM5, E2F2, CDK2, TFDP1, MCM6, CCND1, MAD2L1, MCM2, MCM7, ANAPC5, CCNE1, CDKN2C, CHEK2, E2F3, ORC6, CDC45, ORC1, PKMYT1, CDC25A, MAD2L2, CCND3, CCND2 | WEE2, STAG1, ATM, CDKN2B | 4.03 × 10−6 | 30 | |
Base excision repair | PCNA, PARP1, UNG, POLD1, POLE2, POLD2, LIG1, POLE3, POLD3, NTHL1, NEIL2 | NEIL1, OGG1 | 8.87 × 10−6 | 13 | |
Pyrimidine metabolism | TYMS, NME1, TK1, NME4, DUT, DTYMK, UCK2, CAD, NME2, DCK, UPP1, TK2, DCTPP1, DHODH, CDA | ENTPD8, AK9 | 2.92 × 10−5 | 17 | |
Mismatch repair | PCNA, POLD1, POLD2, RFC4, RFC3, EXO1, RPA3, LIG1, POLD3, RFC2 | − | 3.57 × 10−5 | 10 |
Gene | Length (bp) | Primer Sequence |
---|---|---|
β-actin | 19 | F: CCTTCCTGGGCATGGAGTC |
21 | R: TGATCTTCATTGTGCTGGGTG | |
MCM3 | 19 | F: AAGCAGATGAGCAAGGATG |
19 | R: CAAGAGCAAGCAGAGGATT | |
MCM4 | 17 | F: CACCTGGTCGCACTGTA |
17 | R: GGCTGGCTTCCTCACTT | |
PCNA | 22 | F: ACACTAAGGGCCGAAGATAACG |
22 | R: ACAGCATCTCCAATATGGCTGA | |
POLE2 | 17 | F: TGGTGGAAGCAGCAGTC |
21 | R: GGTTGGTCATTAACAGAGGAA | |
POLD2 | 17 | F: CTGGTGGATGTGGTGAC |
17 | R: CTGTGGCTGAGGAGGTT | |
RPA3 | 21 | F: AGCTCAATTCATCGACAAGCC |
22 | R: TCTTCATCAAGGGGTTCCATCA | |
RAD51 | 22 | F: CAACCCATTTCACGGTTAGAGC |
21 | R: TTCTTTGGCGCATAGGCAACA | |
BID | 17 | F: CGTCCTTGCTCCGTGAT |
18 | R: TGTCCGTTCAGTCCATCC | |
ATM | 19 | F: ACTACTGCTCCAGACCAAT |
20 | R: TCACGACGATACAAAGAACA | |
CDKN2C | 15 | F: CTGAGCGGCATTAGC |
15 | R: CGAACGGGAGTAGCA | |
E2F2 | 18 | F: GCACTGGCATCATTCTCT |
18 | R: AGTCACCTCTGTCCTTGG | |
CCND2 | 19 | F: ACCTTCCGCAGTGCTCCTA |
19 | R: CCCAGCCAAGAAACGGTCC | |
SERPINE1 | 17 | F: GCTGGTGCTGGTGAATG |
17 | R: AGTGCTGCCGTCTGATT |
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He, Y.; Yin, X.; Dong, J.; Yang, Q.; Wu, Y.; Gong, Z. Transcriptome Analysis of Caco-2 Cells upon the Exposure of Mycotoxin Deoxynivalenol and Its Acetylated Derivatives. Toxins 2021, 13, 167. https://doi.org/10.3390/toxins13020167
He Y, Yin X, Dong J, Yang Q, Wu Y, Gong Z. Transcriptome Analysis of Caco-2 Cells upon the Exposure of Mycotoxin Deoxynivalenol and Its Acetylated Derivatives. Toxins. 2021; 13(2):167. https://doi.org/10.3390/toxins13020167
Chicago/Turabian StyleHe, Yuyun, Xiaoyao Yin, Jingjing Dong, Qing Yang, Yongning Wu, and Zhiyong Gong. 2021. "Transcriptome Analysis of Caco-2 Cells upon the Exposure of Mycotoxin Deoxynivalenol and Its Acetylated Derivatives" Toxins 13, no. 2: 167. https://doi.org/10.3390/toxins13020167