PIWI-interacting RNAs and PIWI proteins in glioma: molecular pathogenesis and role as biomarkers

Tamtaji, Omid Reza; Behnam, Mohammad; Pourattar, Mohammad Ali; Hamblin, Michael R.; Mahjoubin‐Tehran, Maryam; Mirzaei, Hamed; Asemi, Zatollah

doi:10.1186/s12964-020-00657-z

Cited by 16 publications

(11 citation statements)

References 86 publications

(91 reference statements)

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“…Piwi-interacting RNA (piRNA) was first identified in 2006 and is defined as a small non-coding RNAs that binds specifically to PIWI family proteins in testicular germ cells [ 6 , 7 ]. PiRNA is approximately 30 nucleotides in length and regulates transposon silencing and mRNA turnover, both of which are critical for gametogenesis and germ cell functions [ 8 – 11 ]. Recent studies have shown that piRNA is effectively expressed in both normal somatic cells and cancer cells [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

piRNA-14633 promotes cervical cancer cell malignancy in a METTL14-dependent m6A RNA methylation manner

Xie

Luo

et al. 2022

J Transl Med

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Background Cervical cancer (CC) is one of the most common gynecological tumors that threatens women's health and lives. Aberrant expression of PIWI-interacting RNA (piRNA) is closely related with a range of cancers and can serve as a tumor promoter or suppressor in proliferation, migration and invasion. In this study, the aim was not only to discover differential expression of piRNA in CC tissue (CC cells) and normal cervical tissue (normal cervical epithelium cells), but also to investigate the biological function and action mechanism of piRNA in CC. Methods The DESeq2 approach was used to estimate fold change in piRNA between CC tissue and normal cervical tissue. The relative expressions of piRNAs (piRNA-20657, piRNA-20497, piRNA-14633 and piRNA-13350) and RNA m6A methyltransferases/demethylases were detected using RT-qPCR. After intervention with piRNA-14633 and METTL14 expression, the viability of CaSki cells and SiHa cells was detected by CCK8. CC cell proliferation was detected by colony formation assay. Apoptosis rate and cell cycle were detected by flow cytometry. Transwell assay was performed to detect cell migration and invasion. EpiQuik m6A RNA Methylation Quantification Kit was used to evaluate m6A RNA methylation levels. Expression of methyltransferase-like protein 14 (METTL14), PIWIL-proteins and CYP1B1 were detected by RT-qPCR and western blot. The effect of piRNA-14633 on METTL14 was evaluated by a dual-luciferase reporter assay. The in vivo effects of piRNA-14633 on CC was assessed by nude mice experiments. Results piRNA-14633 showed high expression in CC tissues and cells, piRNA-14633 mimic (piRNA-14633 overexpression) promoted viability, proliferation, migration and invasion of CaSki cells and SiHa cells. Besides, piRNA-14633 mimic increased m6A RNA methylation levels and METTL14 mRNA stability. Results of dual luciferase reporter assays indicated that METTL14 was a directed target gene of piRNA-14633. Knockdown of METTL14 with siRNA attenuated proliferation, migration and invasion of CC cells. piRNA-14633 increased CYP1B1 expression, while silencing of METTL14 impaired its expression. The effect of piRNA overexpression on METTL14 expression has concentration-dependent characteristics. Results from in vivo experiment indicated that piRNA-14633 promoted cervical tumor growth. Conclusion piRNA-14633 promotes proliferation, migration and invasion of CC cells by METTL14/CYP1B1 signaling axis, highlighting the important role of piRNA-14633 in CC.

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Section: Introductionmentioning

confidence: 99%

piRNA-14633 promotes cervical cancer cell malignancy in a METTL14-dependent m6A RNA methylation manner

Xie

Luo

et al. 2022

J Transl Med

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“…In addition, piRNA plays an important role in gastric cancer, liver cancer, glioma, and other diseases. Based on these correlations, piRNA is expected to serve as a new target for cancer treatment[ 6 , 10 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…P-element-induced wimpy testis (PIWI)-interacting RNA (piRNA) was first found in the ovarian germ cells of Drosophila melanogaster in 2006. This novel short non-coding small RNA has an average length of 26-31 nucleotides[ 5 ] and functions by binding with PIWI protein to form a piRNA-induced silencing complex (PIRISC)[ 6 - 8 ]. piRNA plays an important role in transposon silencing, epigenetic regulation, protein regulation of genome rearrangement, spermatogenesis, and germ stem cell maintenance[ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Expression and role of P-element-induced wimpy testis-interacting RNA in diabetic-retinopathy in mice

Yu¹,

Ren²,

Chen³

2021

WJD

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BACKGROUND As one of the major microvascular complications of diabetes, diabetic retinopathy (DR) is the leading cause of blindness in the working age population. Because the extremely complex pathogenesis of DR has not been fully clarified, the occurrence and development of DR is closely related to tissue ischemia and hypoxia and neovascularization The formation of retinal neovascularization (RNV) has great harm to the visual acuity of patients. AIM To investigate the expression of P-element-induced wimpy testis-interacting RNA (piRNA) in proliferative DR mice and select piRNA related to RNV. METHODS One hundred healthy C57BL/6J mice were randomly divided into a normal group as control group (CG) and proliferative DR (PDR) group as experimental group (EG), with 50 mice in each group. Samples were collected from both groups at the same time, and the lesions of mice were evaluated by hematoxylin and eosin staining and retinal blood vessel staining. The retinal tissues were collected for second-generation high-throughput sequencing, and the differentially expressed piRNA between the CG and EG was detected, and polymerase chain reaction (PCR) was conducted for verification. The differentially obtained piRNA target genes and expression profiles were enrichment analysis based on gene annotation (Gene Ontology) and Kyoto Encyclopedia of Genes and Genomes. RESULTS In the CG there was no perfusion area, neovascularization and endothelial nucleus broke through the inner boundary membrane of retinap. In the EG, there were a lot of nonperfused areas, new blood vessels and endothelial nuclei breaking through the inner boundary membrane of the retina. There was a statistically significant difference in the number of vascular endothelial nuclei breaking through the inner retinal membrane between the two groups. High-throughput sequencing analysis showed that compared with the CG, a total of 79 piRNAs were differentially expressed in EG, among which 43 piRNAs were up-regulated and 36 piRNAs were down-regulated. Bioinformatics analysis showed that the differentially expressed piRNAs were mainly concentrated in the signaling pathways of angiogenesis and cell proliferation. Ten piRNAs were selected for PCR, and the results showed that the expression of piR-MMU-40373735, piR-MMU-61121420, piR-MMU-55687822, piR-MMU-1373887 were high, and the expression of piR-MMU-7401535, piR-MMU-4773779, piR-MMU-1304999, and piR-MMU-5160126 were low, which were consistent with the sequencing results. CONCLUSION In the EG, the abnormal expression of piRNA is involved in the pathway of angiogenesis and cell proliferation, suggesting that piRNAs have some regulatory function in proliferative diabetic-retinopathy.

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“…There is currently no piRNA-based clinical trial, as the study as possible biomarkers has barely begun. Gliomas is the disease in which most progress has been made [ 102 , 187 ].…”

Section: Importance and Future Perspectivesmentioning

confidence: 99%

The Implications of ncRNAs in the Development of Human Diseases

López‐Jiménez

Andrés-León

2021

ncRNA

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The mammalian genome comprehends a small minority of genes that encode for proteins (barely 2% of the total genome in humans) and an immense majority of genes that are transcribed into RNA but not encoded for proteins (ncRNAs). These non-coding genes are intimately related to the expression regulation of protein-coding genes. The ncRNAs subtypes differ in their size, so there are long non-coding genes (lncRNAs) and other smaller ones, like microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs). Due to their important role in the maintenance of cellular functioning, any deregulation of the expression profiles of these ncRNAs can dissemble in the development of different types of diseases. Among them, we can highlight some of high incidence in the population, such as cancer, neurodegenerative, or cardiovascular disorders. In addition, thanks to the enormous advances in the field of medical genomics, these same ncRNAs are starting to be used as possible drugs, approved by the FDA, as an effective treatment for diseases.

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PIWI-interacting RNAs and PIWI proteins in glioma: molecular pathogenesis and role as biomarkers

Cited by 16 publications

References 86 publications

piRNA-14633 promotes cervical cancer cell malignancy in a METTL14-dependent m6A RNA methylation manner

piRNA-14633 promotes cervical cancer cell malignancy in a METTL14-dependent m6A RNA methylation manner

Expression and role of P-element-induced wimpy testis-interacting RNA in diabetic-retinopathy in mice

The Implications of ncRNAs in the Development of Human Diseases

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