piRNAs/PIWI proteins | Clinical relevance | Disease/abnormality | Confirmed/putative molecular mechanisms | References |
---|---|---|---|---|
piR-DQ541777 | N/A | Spine morphogenesis defects | Targets Cdk5rap1 and Mark1/2 | [14] |
Hiwi | Altered hiwi expression had poorer prognosis | Lung, pancreatic, gastrointestinal, liver, breast, colorectal, and ovarian cancer | Influences Stat3/Bcl-X and Stat3/cyclinD1 signaling | |
piR-651 | Upregulated. Potential biomarkers | Gastric, hepatic, breast, stomach, cervical, lung cancer, etc. | – | [42] |
piR-823 | Downregulated | Gastric cancer | – | [43] |
piR-DQ596670 piR-DQ598183 piR-DQ597341 piR-DQ598252 piR-DQ596311 piR-DQ598677 piR-DQ597960 piR-DQ570994 | Misregulated in tumor tissue | Breast cancer | – | [45] |
piR-20365 piR-4987 piR-20582 piR-20485 | Misregulated in tumor tissue among which piR-4987 expression correlates with lymph node metastasis | Breast cancer | – | [46] |
piR-932 | Potential drug target for inhibiting metastasis | Breast cancer | Stimulates the methylation of Latexin promoter region | [47] |
piR-009051 piR-021032 piR-015249 piR-020541 piR-017061 piR-004153 piR-017716 piR-019914 | Misregulated in tumor tissue. Among the listed piRNAs, 4 and 6 piRNAs are linked with OS and RFS respectively, 2 piRNAs are linked with both OS and RFS | Breast cancer | 306 non–redundant gene targets was predicted for six piRNAs, which are enriched for cell events such as transcription, cell signaling, cytoskeleton organization, etc. | [48] |
piR-360269 | Significantly expressed in breast cancer | Breast cancer cell line MCF7 | Targets SERPINA1 and LRAT | [49] |
139 piRNAs | Among 139 piRNAs, 103 were upregulated, 36 were downregulated, 6 were common for stages I & II, 3 were common for stage II & III, while no common piRNAs for stage I & III. Eight were differentially expressed in all three stages | TNBC | – | [50] |
piR-0211285 | Genetic variant of piR-021285 is linked with increased breast cancer risk | Breast cancer | Affects methylation at four genes: AATF, ARHGAP11A, PIP4K2B and THAP10 | [51] |
19 piRNAs | Misregualted in tumor tissue. Upregulation of the three piRNAs are linked with RCC metastasis, poor cancer-specific survival and late clinical stage | RCC | – | [52] |
235 piRNAs 369 piRNAs piR-30924 piR-57125 piR-38756 | Upregulated Downregulated Three piRNAs below were linked with OS in both non-metastatic and metastatic RCC. piR-38,756 is an independent marker for recurrence and survival prognosis in non-metastatic RCC | RCC | – | [53] |
piR-823 | Downregulation of piR-823 in tumor biopsies, while upregulation of piR-823 in blood serum and urine. Higher piR-823 levels in serum are correlated with advance clinical stages of RCC | RCC | – | [54] |
106 piRNAs 91 piRNAs piR-60152 | Upregulated Downregulated Downregulated | Bladder cancer | piR-60152 targets TNFSF4 | [55] |
piR-25447 piR-23992 piR-28876 piR-22842 piR-23317 piR-26131 piR-23210.1 piR-25447 piR-27729 piR-7193.1 piR-7193.2 piR-27729.1 piR-27730.1 | Three piRNAs on the top were misregulated in tumor group. Ten piRNAs at the bottom were misregulated in metastasis group. | CRC | – | [57] |
piR-823 | Upregulated | CRC | Influences HTRA, IGFBP5, HSP27, HSP60 and HSP70. Influences the transcriptional activity but not the expression of HSF1 by binding directly to HSF1 and promote its phosphorylation at Ser326 | [58] |
piR-1245 | Correlates with advanced disease, metastasis and poor prognosis | CRC | Targets ATF3, BTG1, DUSP1, FAS, NFKBIA, UPP1, SESN2, TP53INP1 and MDX1 | [59] |
piR-DQ596225 piR-DQ596306 piR-DQ596309 piR-DQ596354 | Prognostic markers for the OS and RFS of lung adenocarcinoma and lung squamous cell carcinoma patients | Lung cancer | – | [60] |
piR-55490 | Prognostic marker | Lung cancer | Inhibits Akt/mTOR signaling through binding to mTOR mRNA at 3’UTR and promote its degradation | [61] |
piR-52200 piR-34871 piR-46545 piR-35127 | Misregulated in H1229:RASSF1C | Lung cancer cell line H1229 overexpressing RASSF1C | – | [62] |
piR-L-138 | Upregulated following cisplatin (CDDP)-based chemotherapy | LSCC | Binds directly to p60-MDM2 protein to influence cell apoptosis | [63] |
piR-651 | Upregulated in lung cancer cell lines | NSCLC cell line A549 and HCC827 | – | [64] |
125 piRNAs | Misregulated in HCC compared with cirrhotic tissues | HCC | Predicted RNA targets are involved in key signaling pathways such as hepatocarcinogenesis and HCC progression | [65] |
piR-823 | Misregulated and positively correlated with clinical stage | MM | Affects p16INK4A/ cyclin D1/CDK4/Rb pathway. Influences VEGF secretion and restores p16INK4A expression through changing DNA methylation status | [66] |
61 piRNAs | Misregulated | HNSCC | – | [67] |
87 piRNAs | Misregulated. 41 out of the 87 piRNAs correlate with HPV infection status. 5 piRNAs correlate with worse OS | HPV-positive HNSCC | – | [68] |
30 piRNAs | Misregulated | HPV16 (+) HNSCC | Targets PIWIL4 and RTL family of retrotransposon like genes | [69] |
13 piRNAs | 2 piRNAs are linked with tumor stage while 1 piRNA (NONHSAT067200) is a potential indicator of patient survival rate | HNSCC patients with smoking hostory | – | [70] |
10 piRNAs | 2 piRNAs are downregulated and 8 piRNAs are upregulated | Endometrium cancer | 1526 putative mRNA targets were predicted among which 170 were aberrantly expressed in endometrium cancer tissue. The protein encoded takes parts in cell death, growth and survival | [72] |
piR-598 | harbor glioma-associated germline variants | glioma | – | [73] |
piR-593,109 | Upregulated | GEC | Affects MEG3/miR-330-5p/RUNX3 signaling | [74] |
525 piRNAs | Common in two NB cell lines | NB | 589 putative target mRNAs were found. Protein encoded are associated with 185 biological functions relevant to tumorigenesis | [75] |
piR-017061 | Downregulated | PDAC | – | [76] |
125 piRNAs | Upregulated | AD | Target LIN7C, RAB11A, CYCS and KPNA6 | [77] |
103 piRNAs | Misregulated. Potential risk biomarkers | AD | – | [79] |
105 piRNAs | Misregulated | transient focal ischemia | – | [80] |
287 piRNAs | Upregulated | Mecp2 null brain (model for RTT) | – | [81] |
22 piRNAs piR-2106027 | Misregualted Upregulated Potential diagnostic marker | Cardiac hypertrophy | – | [82] |
959 piRNAs | 951 piRNAs are downregulated 8 piRNAs are upregulated | Non-obstructive azoospermia | Putative targets are involved in cellular events such as cell proliferation apoptosis and differentiation | [87] |
347 piRNAs | 128 piRNAs are upregulated and 219 piRNAs are downregulated in islets from GK rats | Diabetes | Putative targets of piR- DQ732700 and piR- DQ746748 are involved in insulin secretion, insulin action or carbohydrate digestion | [88] |
24 piRNAs | Misregulated | UL | – | [89] |