Table 2 Roles of piRNA/PIWI proteins in epigenetic modifications
From: Novel roles of PIWI proteins and PIWI-interacting RNAs in human health and diseases
Type of methylation | piRNA/piwi | Expression | Diseases | Mechanism | In vitro | In vivo | Ref. |
|---|---|---|---|---|---|---|---|
DNA methylation | piRNA-823 | up | Multiple Myeloma | Upregulate the expression of DNMT3B, promote global DNA methylation and decrease tumor suppressor p16INK4A | Promote the cell stemness of MMSCs and lead to abnormal proliferation, anti-apoptosis and tumorigenesis. | Enhance MM growth, tumor burden and angiogenesis | [129] [111] |
DNA methylation | piRNA-823 | up | ESCC | NA | NA | NA | [130] |
DNA methylation | piRNA-823 | up | Breast Cancer | Upregulate the expression of DNMT1, DNMT3A, and DNMT3B, then promote methylation of the APC promoter, and mediates Wnt pathway activation | Promoted cell proliferation and cell Stemness | Promote tumor growth | [131] |
DNA methylation | piRNA-823 | down | Gastric Cancer | Reduce tumor suppressor genes methylation, and then causes cells aberrant “stem-like” state | Suppress tumor cell growth | Reduce tumor weight | [132] |
DNA methylation | piR_011186 | up | Acute Leukemia | Promote DNA methylation of CDKN2B promoter | Promote cell cycle progression, and reduce apoptosis | NA | [133] |
DNA methylation | piR-31,470 | up | Prostate Cancer | Recruits DNMT1, DNMT3α and MBD2 to induce hypermethylation of GSTP1 | Promote cell proliferation | NA | [134] |
DNA methylation | piR-651 | up | Breast Cancer | Increases PTEN promoter region methylation and restrain its expression | Promote cell proliferation and invasion, and inhibit apoptosis | NA | [135] |
DNA methylation | piRNA-63,076 | up | Pulmonary arterial hypertension | Upregulate levels of DNMT1 and DNMT3A, increase the methylation of Acadm promoter and result in the inhibition | Increase the proliferation of pulmonary arterial smooth muscle cells | NA | [136] |
DNA hypomethylation | PIWIL1 | up | Endometrial Cancer | PIWIL1 promoter hypomethylation | Promote cell growth | NA | [137] |
DNA hypermethylation | PIWIL1 | up | Endometrial Cancer | Induce PTEN hypermethylation and inhibit the expression | NA | NA | [138] |
DNA methylation | PIWIL2 | down | Cerebral ischemic injury | PIWIL2 knockdown leads to a significant reduction in DNMT3A, which in turn will eliminate CREB2 DNA methylation and increase CREB2 expression | Prevent dentate spine loss | NA | [139] |
m6A methylation | piRNA-30,473 | up | DLBCL | WTAP promotes the stable expression of its downstream target HK2 by increasing its m6A level | Promote cell proliferation | Promote tumor growth | [140] |
m6A methylation | piRNA-14,633 | up | Cervical Cancer | Highly expressed METTL14 promotes m6A methylation of CYP1B1 | Promote cell proliferation, migration and invasion | Promote cancer growth | [141] |
m6A methylation | piRNA-17,560 | up | Breast Cancer | Strengthen ZEB1 transcripts stability and expression by decreasing m6A RNA methylation | Promote the proliferation, EMT and chemoresistance | Increase drug resistance and tumor volume after chemotherapy | [112] |
m6A methylation | piRNA-36,741 | up | Osteoblast differentiation | piR-36,741 trapped METTL3 to prevent it from binding to BMP2 mRNA, thereby reducing m6A methylation of BMP2 | Promote osteogenic differentiation | Alleviate ovariectomy-induced osteoporosis in mice | [121] |
m6A methylation | piR-141,981 | up | Cardiac hypertrophy | CHAPIR captures METTL3 to prevent its binding to PARP10 mRNA and reduces the m6A methylation of PARP10 | Promote cardiomyocyte hypertrophy | Promote cardiomyocyte hypertrophy | [142] |