Background
piRNA biosynthesis mechanism
Transcription of piRNA clusters
Two major pathways generate piRNAs
piRNA/piwi protein function and mechanism in cancer
piRNAs/piwi complex-mediated transcriptional gene silencing (TGS)
piRNAs/piwi complex- mediated post-transcriptional gene silencing (PTGS)
piRNAs/piwi complex interaction with proteins
piRNAs in cancer
piRNA | Cancer type | Function | Expression in tumors | Reference |
---|---|---|---|---|
piR-36712 | Breast cancer | suppressed cell proliferation, invasion and migration by combining with SEPW1P RNA | down | [22] |
piR-021285 | inhibited cell proliferation and invasion by ARHGAP11A methylation | down | [35] | |
piR-932 | caused EMT through promoting promoter region CpG island methylation of Latexin | up | [46] | |
piR-DQ598677 | form pi-RISC to degrade targeted genes like miRNAs | down | [47] | |
piR-34871 piR-52200 | Lung cancer | correlated with RASSF1C expression, promoted cell proliferation and colony formation by reducing AMPK phosphorylation of ATM-AMPK-p53-p21cip pathway | up | [17] |
piR-35127 piR-46545 | down | |||
piR-651 | Promoted cells and tumor proliferation and inhibited apoptosis, induced cyclin D1 and CDK4 expression | up | ||
piR-55490 | inhibited LC cells and tumor proliferation by binding 3’UTR of mTOR mRNA | down | [37] | |
piR-823 | Gastric cancer | inhibited proliferation of cancer cells, and caused cells aberrant “stem-like”state by weakening tumor supporter genes methylation | down | |
piR-651 | promote cell proliferation and associated with TNM stages | up | [51] | |
piR- FR222326 | positively associated with overall survival | up | [52] | |
piR-FR290353 piR-FR064000 piR-FR387750 | associated with recurrence-free survival | up | [52] | |
piR-1245 | Colorectal cancer | accelerated cell growth, promoted migration and invasion as well as anti-apoptosis by binding to its downstream targeted mRNA in nuclear exosomes, associated with poor differentiation, TNM state and poor overall survival | up | [53] |
piR-54265 | promoted proliferation and metastasis, inhibited apoptosis, correlated with shorter progression-free survival time and overall survival time, caused therapy resistance to anti-tumor agents by regulating STAT3 phosphorylation | up | [45] | |
piR-823 | enhanced cells proliferation and suppressed apoptosis by promoting HSF1 phosphorylation at Ser326 and inducing Stat3 phosphorylation | up | [44] | |
piR-015551 | influenced the colorectal cancer development by causing gene mutation | up | [54] | |
piR-Hep1 | Hepatocellular carcinoma | promoted cells proliferation and invasion via upregulating phosphorylated AKT of PI3K/AKT signaling pathway | up | [55] |
piR-LLi-24894 | asssociated with low-grade lesions of hepatocellular carcinoma | up | [56] | |
Hsa-piR-013306 | involved in the hepatic carcinogenic process | up | [56] | |
piR-32051 piR-39894 piR-43607 | Kidney cancer | linked with renal cell carcinoma of high tumor stage and metastasis and cancer-specific survival | up | [57] |
piR-57125 | inhibited cancer metastatic | down | [58] | |
piR-30924 piR-38756 | associated with cancer metastatic | up/down | [58] | |
piR-823 | Hematological malignancy | promoted proliferation, inhibited apoptosis and modulated cell cycle progression of multiple myeloma cells by regulating DNA methylation and angiogenesis | up | [36] |
improved the survival and maintained the stemness of multiple myeloma stem cells by producing more DNMT3B | up | [59] | ||
promoted the proliferation, migration, and capillary structure formation of tumor-associated endothelial cells | up | [60] | ||
piR-651 | associated with shorter disease-free survival and shorter overall survival in classical Hodgkin lymphoma patients | up | [61] | |
piR-30188 | Glioblastoma | supressed tumor cell proliferation, invasion and migration and promoted apoptosis by binding to OIP5-AS1 | down | [38] |
piR-8041 | Promoted cells proliferation and inhibited death by interacting with the mRNA MAPK | down | [62] | |
piR-DQ593109 | increased the permeability of the blood-tumor barrier and promoted the delivery of therapeutics into the glioma micro-environment via bindind to MEG3 | down | [63] | |
piR-DQ590027 | increased the permeability of glioma-conditioned normal blood-brain barrier and promoted the transport of macromolecular chemotherapeutics into glioma tissues by binding to MIR17HG | down | [64] | |
piR-39980 | Fibrosarcoma | inhibition of cell proliferation via interacting with RRM2 | down | [65] |
piR-52207 | Ovarian cancer | promoted cell proliferation, migration and tumorigenesis by binding to targeted mRNA (NUDT4, MTR, EIF2S3, MPHOSPH8) | up | [66] |
piR-33733 | Inhibited cells apoptosis by binding to targeted mRNA (ACTR10, PLEKHA5) | up | [66] | |
piR-017061 | Pancreatic cancer | Not clear | down | [67] |
Breast cancer (BC)
Lung cancer(LC)
Gastric carcinoma (GC)
Colorectal cancer (CRC)
Hepatocellular carcinoma (HCC)
Kidney cancer(KC)
Hematological malignancies
Glioblastoma
Other cancers
piRNAs as biomarkers in cancer
piRNA | Cancer | Expression in blood | Clinical correlation | ROC curve AUC sensitivity specifity | Reference |
---|---|---|---|---|---|
piR-651 | Gastric cancer | down | TNM stage, distant metastasis | 0.841 0.709 0.813 | [101] |
piR-823 | down | TNM stage, distant metastasis | 0.822 0.805 0.812 | [101] | |
piR-5937 | Colorectal cancer | down | TNM stage | 0.806 0.718 0.725 | [102] |
piR-28876 | down | TNM stage | 0.8065 0.753 0.700 | [102] | |
piR-54265 | up | TNM stage, survival times and curative efficacy of chemotherapy | 0.811 0.667 0.885 | [45] | |
piR-823 | Renal cell cancer | up | TNM stages | – | [103] |
piR-823 | Multiple myeloma | up | TNM stages | – | [60] |
piR-651 | classical Hodgkin lymphoma | down | the presence of lymphoma | – | [61] |
Piwi proteins and cancer
PIWIL1(HIWI)
PIWI | Cancer | Expression | Function | Reference |
---|---|---|---|---|
PIWIL1 | Lung cancer | up | DNA hypomethylation | [105] |
Gastric cancer | up | Regulate signaling pathway of gastric cancer | [106] | |
Colorectal cancer | up | be used as an important molecular marker for predicting the prognosis of CRC patients | [107] | |
Renal cell cancer | down | serve as potential prognostic biomarkers in patients with RCC | [103] | |
Endometrial cancer | up | become a valuable target for developing a novel treatment; DNA methylation | ||
Invasive ductal carcinoma | up | aberrant DNA methylation | [110] | |
PIWIL2 | glioma | up | correlated with the poor prognosis | [111] |
cervical cancer | up | induced H3K9 acetylation but reduced H3K9 trimethylation, | [112] | |
Non-small cell lung cancer | up | increasing the expression of CDK2 and CyclinA | [113] | |
Renal cell cancer | down | connected with bad survival | [103] | |
PIWIL3 | Glioma | down | regulate PIWIL3/piR-30,188/OIP5-AS1/miR-367-3p/CEBPA/TRAF4 pathway | [38] |
Gastric cancer | up | regulate JAK2/STAT3 signaling pathway | [114] | |
Multiple myeloma | up | involve in MM progression and metastatic | [115] | |
PIWIL4 | Triple-negative breast cancer | up | activating TGF-β, MAPK/ERK, and FGF signaling and avoiding immune recognition | [116] |
PIWIL2(HILI)
PIWIL3(HIWI3)
PIWIL4(HIWI2)
Conclusion
Common Assays | Objective of Assays | Reference |
---|---|---|
High-throughput Sequencing (HTS) | Assaying new and known piRNAs | |
Reverse Transcription-quantitative PCR (RT-qPCR) | Assaying exact piRNA copy number per cell and the relative expression | [22] |
Southern Blot | Assaying exact piRNA copy number | [53] |
Nouthern Blot | Assaying the number of nucleic acids of piRNA | [22] |
RNA binding protein immunoprecipitation (RIP) | Assaying the interaction of piRNA-proteins | |
RNA Pull Down | ||
Luciferase reporter system | Assaying the interaction of piRNA-target RNA | |
Microarray assay | Assaying DNA methylation by piRNAs, | [45] |