Table 1.
Interaction between miRNAs and arsenic compounds.
| miRNA | Human/animal Study | Dose | Cell line | Dose | Targets | Observations | Ref |
|---|---|---|---|---|---|---|---|
| miR-15a, miR-16-1 (−) | Raji, HL60, RPMI8226, K562, U937 | 1 μM, for 48 h | Caspase-3, Cytochrome-c | In K562 cells, both mentioned miRNAs could sensitize apoptosis induced by ATO. | [31] | ||
| miR-21 (−) | – | – | K562 | 0.5–4.0 μM, 4 h | PDCD4 | The sensitization of K562 cells exposed to ATO increased because of the anti-miR-21 oligonucleotide. | [32] |
| miR-21, miR-200b, miR-191, miR-155, miR-145 (Up) | Human | – | – | – | – | Exposure to arsenic by elevating the expression of mentioned miRNAs could lead to multiorgan (such as skin, liver, and kidney) damage. | [33] |
| miR-21, miR-155, miR-200b (Up) | miR-21 knockout mice, wild-type mice | 20 ppm, 6 months | HBE, MRC-5 | 0–8 μM, 24 h | PTEN, AKT, α-SMA | In the pulmonary fibrosis model induced by NaAsO₂, miR-21 via glycolysis could elevate the differentiation of myofibroblast. | [34] |
| miRNA profile, miR-29a (−) | – | – | HepG-2 | 0–6 μM, 24 h | Wip-1, PPM1D | In HepG-2 cells, miR-29a could mediate ATO induction of cell death. | [35] |
| miR-27a (Down) | – | – | MDA-MB-231, SK-BR-3 | 0–14 μM, for 24 h | Fbw7, Cyclin-E | In breast cancer cells, ATO via suppressing miR-27a could inhibit tumorigenesis. | [36] |
| miR-31 (Down) | – | – | BEAS-2B | 0–10 μM, 48 h, 2 μM, 6 weeks | SATB2 | Arsenic via reducing miR-31 and elevating SATB2 could induce malignant transformation in BEAS-2B cells. | [37] |
| miR-34a, miR-133b, (Down) | Human | – | U251, SH-SY5Y | 5 or 10 μM, 24 h | hERG | miR-133b via sponging the hERG could lead to apoptosis. | [38] |
| miR-98 (Up) | SD rats | 0.4 mg/kg, 2 weeks | A549 | 0–10 μM, for 48 h | Stat3, α-SMA, E-cadherin, Bax, Bcl-2 | Pulmonary fibrosis induced by bleomycin could be decreased after ATO treatment via increasing miR-98 expression. | [39] |
| miR-126 (Down), miR-155 (−) | Human (Mexican children) | – | – | – | – | Inorganic arsenic could change the expression of miR-126. | [40] |
| miR-148a (Up) | – | – | Multiple drug-resistant (MDR) Bel-7402 | 0–3.5 μM, 24 h | NF-κB | ATO via demethylating miR-148a and suppressing the NF-κB could promote cell sensitivity to chemotherapeutic agents. | [41] |
| miR-155 (Up) | Mice | 2 mg/kg, 2/week, 2 months | PC-3, HUVEC, LNCaP | 0–4 μM, 48 h | VEGF, TGF-β, SMAD | In prostate cancer, ATO could induce anti-angiogenic effects via elevating miR-155 and suppressing the TGF-β/SMAD pathway. | [42] |
| miR-155 (Up) | – | – | A549, A549R | 0–30 μM, 0–150 μM, 72 h | HO-1, Nrf-2, NQO1, Bax, NQO1 | miR-155 via suppressing apoptosis and enhancing Nrf2 could mediate cell resistance to ATO. | [43] |
| miR-184, miR-576-3p, (−) | Human | 59–172 ppb | – | – | – | In skin lesions (west Bengal people) induced by arsenic, the expression of miRNAs could change. | [44] |
| miR-190 (Up) | – | – | BEAS-2B, A549 | 0–20 μM (6 h), | PHLPP, AKT, Talin-2 | Exposed cells to AsCl3 by activating AKT, elevating miR-190, and suppressing PHLPP could lead to carcinogenesis. | [45] |
| miR-191 (Up) | Human | – | – | – | IL-2/6, TGF-β, TNF-α | miR-191 via activating inflammatory response could lead to renal dysfunction induced by coal-burning arsenic. | [46] |
| miR-199a-5p (Down) | Female CrTac: NCrFoxn1nu mice | – | AsT, BEAS-2B | 0–2 μM (24 h), | HIF-1α, COX-2 | Overexpression of miR-199a via targeting COX-2 and HIF-1α could suppress angiogenesis in bronchial epithelial cells. | [47] |
| miR-203 (−) | – | – | K562 | 1.25–20 μg/mL, 48 h | Caspase-3/9, Cytochrome-c | hsa-miR-203 could increase leukemia cell sensitivity to ATO. | [48] |
| miR-222 (Up) | – | – | BEAS-2B | 1 μM, 26 weeks | ARID1A, PTEN, AKT | Administration of anti-miR-222 could inhibit tumor growth induced by arsenic. | [49] |
| miR-301a (Up) | Athymic nude mice | – | BEAS-2B, BEAS-2B–As | 0–10 μM 12 h | SMAD4, IL-6, STAT3 | NaAsO₂ via increasing miR-301a could lead to malignant transformation of BEAS-2B cells. | [50] |
| miR-425-5p (Down) | C57BL/6J mice | (0, 1, or 10 ppm), 3 months | HUVECs, 293T | 1–40 μM, for 24–48 h | CCM3, Notch, VEGF/p38 | NaAsO2 had anti-angiogenesis effects in HUVECs. | [51] |
| miR-539 (Down) | Human, Male athymic nu/nu mice | 5 mg/kg, one injection/3 days, 18 days | Primary human hepatocytes, HepG2, Hep3B, Huh7, PLC/PRF/5, Sk-Hep-1, PLC-ATR, HepG2-ATR | 0–64 μM, for 48 h | Stat3, Bcl-2, Bcl-xL | In hepatocellular carcinoma, miR-539 could decrease cell chemoresistance induced by ATO. | [52] |
| miR-1294 (Up) | female BALB/C athymic nude mice | Huh6/7, HepG2, SMMC7721, Hep3B | 0–12 μM, 48 h | TEAD1, PIM1, caspase-3, Bax, Bcl-2 | In hepatocellular carcinoma, arsenic trioxide via upregulating miR-1294 and sponging PIM1/TEAD1 axis could inhibit tumor growth. | [53] | |
| miR-2909 (Up) | – | – | PBMCs | 0.5–2 μM, 72 h | Cyclin-D1, SP1 KLF4, NF-kB, BCL3 | Arsenic via miR-2909 could mediate the regulation of Cyclin-D1. | [54] |
| miR-4665-3p (Down) | Human (gastric cancer patients) | – | MGC803, AGS, HCT116 | 133.36 (stock solution) μM, 24 h | GSE-1, VEGF, E-cadherin, Vimentin | As4S4 via increasing miR-4665-3p could suppress migration or invasion in gastric cancer cells. | [55] |