Table 2.
Interaction between miRNAs and cadmium compounds.
| miRNA | Human/animal Study | Dose | Cell line | Dose | Targets | Observations | Ref |
|---|---|---|---|---|---|---|---|
| novel-miR-6, (Down), miR-27a-5p (Up), miR-122 (Down) | Common carp | 0.275 mg/L, 1 month | – | – | Caspase-9, Bax, Bak, Bcl-2 | In carp exposed to CdCl2, miRNA changes could be a biomarker. | [56] |
| 17 upregulated miRNAs (such as miR-7-1-5p) and 6 downregulated miRNAs (such as miR-9-6-5p) | Juvenile fish | 0.26 mg/L, 96h | – | – | MAPK, Jak/STAT, NF-κB, IL-4/13A, COX-2, PTGES, | CdCl2 in common carp spleens via targeting miRNA-mRNA networks could lead to inflammation. | [57] |
| miR-9a-5p, miR-29a-3p, miR-204-5p (Up) | Female SD rats | – | Rat ovarian granulosa cells, PC-12 | 0–20 μM, h | Bcl-2, Bax, Fas | Exposure to CdCl2 in rat ovarian granulosa cells via miR-204-5p and Bcl-2 could regulate apoptosis. | [57] |
| miR-21, miR-29b, (Up) | Human, SD rats | 2.0 mg/kg, 2 weeks | – | – | – | The expression of miR-21 could be a potential biomarker for the dysfunction of the kidney. | [58] |
| 44 upregulated (such as miR-21-5p, miR-3084c-3p), 54 downregulated (such as miR-455-3p, miR-193b-3p) | Male SD rats | 0.6 mg/kg, 5 days a week,3 months | – | – | – | CdCl2 could induce nephrotoxicity and change the expression of miRNAs. | [59] |
| miR-25-3p (Down) | juvenile common carp | 0.26 mg/L, 45 days | – | – | Hsp70/90, AMPK, PTEN, ULK1, mTOR, Atg-5/12, Beclin-1, LC3-II | Pollutants with CdCl2 in common carp could lead to autophagy and oxidative stress via miR-25-3p. | [60] |
| miR-26a, miR-155, (−) | Human | – | JEG-3 | 1–25 μM, 24–48 h | TGF-β, Smad-2/3 | miRNAs could regulate the TGF-β pathway in trophoblast cells exposed to cadmium. | [61] |
| miR-26a (−) | – | – | JEG-3 | 0–25 μM, 48 h | TGF-β | The migration of placental trophoblast cells could be inhibited by exposure to CdCl2 via the miR-26a/TGF-β axis. | [62] |
| miR-27b-3p (Up), miR-877-5p (Down) | – | – | 16HBE | 5 μmol/L, 14 weeks | CCM2 | Mentioned miRNAs could act as malignant transformation. | [24] |
| miR-30 family (a, b, d, c, e) (Down) | – | – | BEAS-2B, BEP2D | 0–10 μM, 72 h | SNAIL, ZEB1, Vimentin, E-cadherin | In human lung epithelial cells, exposure to CdCl2 via suppressing miR-30 could promote SNAIL and fibrosis. | [63] |
| miR-33-5p (Down) | Hy-Line Brown laying hens | 150 mg/kg, 3 months | – | – | BNIP3, LC3-I/II, Beclin-1, AMPK, AKT/mTOR, NF-kB/JNK, | In the chicken spleen, CdCl2 via regulating AMPK and miR-33 could induce autophagy, dependent on BNIP3. | [64] |
| miR-34a (Up) | Male Kunming mice | 1.5 mg/kg, 1 month | – | – | Sirt1, p53, Bax, Bcl-2, IL-1β Caspase-9, | miR-34a via targeting p53 or Sirt1 could induce nephrotoxicity. | [65] |
| miR-34a (Up) | Male Wistar rats | 10 mg/L | – | – | SIRT1, p53, IL-6, TNF-α, SREBP1/2, | The non-alcoholic fatty liver disease could be induced in an animal model by CdCl2. | [66] |
| miR-92a-2-5p (Down), miR-181b-5, (Up) | SD rats | 0.5–8 mg/kg | granulosa cells | 0–20 μM, 12 h | Bcl-2, Bax | miRNA profile could be changed in ovarian granulosa cells of rats exposed to CdCl2 during the prenatal period. | [67] |
| miR-92a-2-5p (Up) | Female SD rats | 8 mg/kg, postnatal day [56] | granulosa cells, COV434 | 0–20 μM, 24 h | c-Myc, Bcl-2, DNMT3B, DNMT1, DNMT3A | After cadmium exposure, in rat ovarian granulosa cells, c-Myc could promote the transcription of miR-92a-2-5p. | [68] |
| miR-101 (Down) | – | – | HUVECs | 0–80 μM, 0–36 h | COX-2, VEGF, eIF2α | miR-101 by sponging COX-2 could suppress angiogenesis induced by CdCl2 in HUVECs. | [69] |
| miR-122 (Down) | farmed tilapia | 12 mg/L, 24 h | – | – | MT 3′UTR | miR-122 via sponging metallothionein gene could act against hepatic oxidants induced by CdCl2. | [70] |
| miR-122-5p, miR-326-3p, (Up) | Human, Male SD rats | 0.6 mg/kg, 3 months | HK-2, NRK-52E | 9.18 and 10 μM, 48 h | – | Both mentioned miRNAs could be an early detective biomarker for CdCl2 exposure. | [71] |
| miR-122-5p, miR-326-3p, (Up) | SD rats | 0.6 mg/kg, 1.5 months | NRK-52E | 10 μM, 48 h | PLD1 | Both mentioned microRNAs via decreasing PLD1 could increase apoptosis in NRK-52E cells treated with CdCl2. | [72] |
| miR-143-3p (Up) | Human | – | hBMSCs | 0–30 μM, 7–24 h | Wnt/β-catenin, ARL6, ALP, RUNX2, LEF1, TCF1 | In hBMSCs exposed to CdCl2, miR-143-3p via targeting ARL6 could inhibit osteogenic differentiation. | [73] |
| miR-155, miR-181a, (Up) | Common carp | 0.005–0.5 mg/L, 1 month | – | – | HO-1, NF-κB, TLR-4, IL-1β, IL-8/10 | Both mentioned miRNAs via targeting HO-1 could lead to immunotoxicity in the carp's kidneys. | [74] |
| miR-155 (−), miR-221 (Down) | Human | – | – | – | IL-17, TNF-α | In workers exposed to CdCl2, there is an association between miRNAs and immune markers. | [75] |
| miR-217 (−) | Common carp | 0.005–0.5 mg/L, 1 month | – | – | SIRT1, TLR-4, NF-kB, TRAF6 | In common carp exposed to CdCl2, the miR-217/SIRT1 axis could lead to immunotoxicity. | [76] |
| miR-363-3p (Up) | Human (occupational chronic Cd poisoning) | – | HK-2, NRK-52E | 0–64 μM, 48 h | PI3K, PARP, Caspase-3 | miR-363-3p via suppressing PI3K could enhance cell death in the kidney. | [77] |
| miR-381 (Down) | – | – | HBEC | 1 μM | EZH2, H3K27me3 | In epithelial cells exposed to CdCl2, the miR-381/EZH2 axis could regulate the expression of the chloride channel. | [78] |
| miR-503-5p (Down) | SD rats | 0.6 mg/kg, 6 or 12 weeks | NRK-52E | 6–10 μM, 24 h | Wnt/β-catenin, α-SMA, Vimentin, Collagen1 | CdCl2 could induce kidney fibrosis and EMT via suppressing miR-503-5p and promoting the Wnt/β-catenin pathway | [79] |
| miR-6769b-5p (Up) | Human, male and female CD-1 mice | 2.5 mg/kg on the 15th gestational day | HTR-8/SVneo, | 0–40 μM, for 24 h | CCND1, PCNA | miR-6769b-5p via sponging CCND-1 could be involved in the proliferation of placental trophoblasts treated with CdCl2. | [80] |