更新于：2024-09-19

PIWIL3

更新于：2024-09-19

基本信息

别名

HIWI3、piwi like RNA-mediated gene silencing 3、Piwi-like protein 3

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简介

May play a role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Directly binds piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation (By similarity).

关联

100 项与 PIWIL3 相关的临床结果

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100 项与 PIWIL3 相关的转化医学

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0 项与 PIWIL3 相关的专利（医药）

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项与 PIWIL3 相关的文献（医药）

2024-02-08·Cancer Biomarkers

Elevated expression patterns of P-element Induced Wimpy Testis (PIWI) transcripts are potential candidate markers for Hepatocellular Carcinoma

Article

作者: Safwat, Gehan ; Seleem, Mohamed Ismail ; Mamdouh, Samah ; Seoudi, Dina Mohamed ; Mohamed, Rania Hassan ; Hammad, Gehan

BACKGROUND: P-Element-induced wimpy testis (PIWI) proteins, when in combination with PIWI-interacting RNA (piRNA), are engaged in the epigenetic regulation of gene expression in germline cells. Different types of tumour cells have been found to exhibit abnormal expression of piRNA, PIWIL-mRNAs, and proteins. We aimed to determine the mRNA expression profiles of PIWIL1, PIWIL2, PIWIL3, & PIWIL4, in hepatocellular carcinoma patients, and to associate their expression patterns with clinicopathological features. METHODS: The expression patterns of PIWIL1, PIWIL2, PIWIL3, PIWIL4 mRNA, was assessed via real-time quantitative polymerase chain reaction (RT-QPCR), on tissue and serum samples from HCC patients, their impact for diagnosis was evaluated by ROC curves, prognostic utility was determined, and In Silico analysis was conducted for predicted variant detection, association with HCC microRNAs and Network Analysis. RESULTS: Expression levels were significantly higher in both HCC tissue and serum samples than in their respective controls (p< 0.001). Additionally, the diagnostic performance was assessed, Risk determination was found to be statistically significant. CONCLUSION: PIWIL mRNAs are overexpressed in HCC tissue and serum samples, the expression patterns could be valuable molecular markers for HCC, due to their association with age, tumour grade and pattern. To the best of our knowledge, our study is the first to report the expression levels of all PIWIL mRNA and to suggest their remarkable values as diagnostic and prognostic biomarkers, in addition to their correlation to HCC development. Additionally, a therapeutic opportunity might be also suggested through in silico miRNA prediction for HCC and PIWIL genes through DDX4 and miR-124-3p.

2023-11-01·Biochimica et Biophysica Acta (BBA) - General Subjects

PIWI interacting RNA-13643 contributes to papillary thyroid cancer development through acting as a novel oncogene by facilitating PRMT1 mediated GLI1 methylation

Article

作者: Liu, Ning ; Zhang, Zhongbo

BACKGROUNDRecently, aberrant expression of PIWI-interacting RNAs (piRNAs) has been discovered in a variety of cancer cells. However, the roles of PIWI proteins and piRNAs in papillary thyroid carcinoma (PTC) are still elusive.METHODSRT-qPCR and Northern blotting were used to evaluate piR-13643 levels in PTC and para-carcinoma tissues, as well as in PTC cell lines. piR-13643 mimic and piR-13643 inhibitor were transfected into K-1 and B-CPAP cells. CCK-8, Transwell, annexin V-FITC/PI, flow cytometry and Western blot assays were performed to measure cell proliferation, invasion, apoptosis, cell cycle and E-cadherin and Vimentin proteins, respectively. Total RNA from B-CPAP cells was pulled down with PIWIL1, PIWIL2, or PIWIL3 specific antibodies or IgG as a control, respectively, followed by detection of piR-13643 expression with RT-qPCR. Immunoblotting of PRMT1 was detected in piR-13643 / PIWIL1 complex immune-precipitates by Co-IP assay. Subsequently, PRMT1 protein expression was detected by stably transfection of Flag tagged GLI1 (Flag-GLI1) into B-CPAP cells. Methylation assay with PRMT1 and wild-type or R597 lysine (R597K)-mutant GLI1. Then rescue experiments were applied to explore effects of piR-13643 and GLI1 on the malignant behavior of PTC cells. B-CPAP cells transfected with piR-13643 inhibitor were subcutaneously injected into nude mice to evaluate the effect of piR-13643 knockdown on the xenograft tumor growth of PTC.RESULTSpiR-13643 was elevated in PTC patient specimens and cell lines. piR-13643 overexpression facilitated cell proliferation, invasion and Vimentin level, and restrained apoptosis and E-cadherin expression, whereas piR-13643 knockdown showed the opposite results. Mechanically, piR-13643 could bind to PIWIL1 to form the PIWIL1/piR-13643 complex, and PRMT1 enhanced GLI1 transcription by methylating GLI1 at R597. Further, PIWIL1/piR-13643 promoted PRMT1-mediated GLI1 methylation. GLI1 knockdown countered the effects of piR-13643 mimic on cell malignant behaviors. piR-13643 knockdown preeminently prevented the xenograft tumor growth of PTC in vivo.CONCLUSIONSThis study confirmed that piR-13643 facilitates PTC malignant behaviors in vitro and in vivo by promoting PRMT1-mediated GLI1 methylation via forming a complex with PIWIL1, which may provide a novel insight for PTC treatment.

2023-10-01·Insect Science

The piRNA pathway is required for nucleopolyhedrovirus replication in Lepidoptera

Article

作者: Guo, Yiyao ; Zhang, Mengmeng ; Xia, Junming ; Sun, Jingchen ; Feng, Min ; Wu, Hongyun ; Yu, Wensheng ; Yang, Yifan ; Fei, Shigang ; Swevers, Luc

AbstractThe Piwi‐interacting RNA (piRNA) pathway has been shown to be involved in the antiviral defense against RNA viruses, especially in mosquitoes, but its universality has been questioned. Here, we used the Bombyx mori nucleopolyhedrovirus (BmNPV) ‐infected silkworm as a model to explore the effects of the key factors of piRNA pathway, BmAgo3 and Siwi, on replication of a large DNA virus (belonging to the family of Baculoviridae). We demonstrated that BmAgo3 and Siwi could promote the replication of BmNPV through both overexpression and knockdown experiments in BmN cell lines and silkworm larvae. In addition, we also studied the effect of PIWI‐class genes on Autographa californica nucleopolyhedrovirus (AcMNPV) replication in the Spodoptera frugiperda cell line Sf9. By knocking down the expression of PIWI‐class genes in Sf9, we found that Piwi‐like‐1 and Piwi‐like‐2‐3 could inhibit AcMNPV replication, while Piwi‐like‐4‐5 promoted virus replication. Our study provides compelling evidence that the piRNA pathway affects host infection by exogenous viruses in Lepidoptera. Also, our results reflect the diversity of the roles of PIWI‐class genes in virus infection of the host across species. This study is the first to explore the interaction of PIWI‐class proteins with DNA viruses, providing new insights into the functional roles of the piRNA pathway.

项与 PIWIL3 相关的新闻（医药）

2023-09-08

·生物谷

研究揭示PIWI亚家族蛋白在哺乳动物配子发生和早期胚胎发育中的非冗余功能

针对上述科学问题，科研人员分别制备和获得了四种PIWI蛋白的特异性抗体，结合超分辨共聚焦显微技术，全面分析了四种PIWI亚家族蛋白在金黄地鼠精子发生、卵子发生和早期胚胎发育中的时空表达特征《自然-通讯》（Nature Communications）在线发表了中国科学院分子细胞科学卓越创新中心吴立刚研究组与南京医科大学李建民研究组合作完成的最新研究成果（The non-redundant functions of PIWI family proteins in gametogenesis in golden hamsters）。该研究以金黄地鼠（Mesocricetus auratus，golden hamster）为动物模型，全面揭示了PIWI家族成员及其结合的piRNA在配子发生和早期胚胎发生中非冗余的调控功能，为研究哺乳动物piRNA功能奠定了重要基础。 piRNA（PIWI-interacting RNA）是一类生殖细胞特异表达的非编码小RNA，与PIWI蛋白形成效应复合体，参与转座子沉默和基因表达调控，在配子发生和受精卵发育过程中发挥广泛而重要的功能。以往对哺乳动物PIWI/piRNA的功能认识主要基于小鼠模型。然而，研究组的前期研究表明小鼠卵细胞中非编码小RNA的组成在哺乳动物中不具有广泛代表性，并首次在人和食蟹猴卵细胞中发现新的piRNA家族成员os-piRNA。近期，包括该研究组在内的三项独立研究表明，piRNA通路重要作用蛋白PIWIL1和MOV10L1（RNA解旋酶）的缺失均可导致金黄地鼠雌雄不育，与小鼠中表型存在明显差别。上述研究证明了小鼠不是研究哺乳动物雌性生殖细胞发育中piRNA功能的最佳动物模型，以往通过小鼠建立的哺乳动物piRNA经典结论需要在更加具有代表性的金黄地鼠中重新研究或加以确认。针对上述科学问题，科研人员分别制备和获得了四种PIWI蛋白的特异性抗体，结合超分辨共聚焦显微技术，全面分析了四种PIWI亚家族蛋白在金黄地鼠精子发生、卵子发生和早期胚胎发育中的时空表达特征，并结合高通量测序技术细致地描绘了不同发育时期中PIWI蛋白所结合的piRNA表达谱。进一步，研究利用CRISPR技术分别构建了四种PIWI缺失的金黄地鼠突变系，探讨了不同PIWI蛋白突变所引发的生殖缺陷表型。结果表明，PIWIL1同时在雌性和雄性生殖细胞及早期胚胎中高表达，主要结合29-30 nt piRNA，突变后导致雌雄均不可育：突变的生精细胞在进入双线期前发生大量死亡，部分可进入双线期的生精细胞随后发育停滞，而突变的卵母细胞可正常发育，但受精后胚胎发育停滞于2细胞时期。PIWIL2和PIWIL4主要在生精细胞中表达，但两者表达存在明显的时期特异性，且分别结合27 nt或28 nt piRNA。PIWIL2或PIWIL4突变后生精过程严重受阻，大量精原细胞凋亡，造成雄性不育。PIWIL3高表达于卵母细胞和早期胚胎中，结合19 nt的os-piRNA，突变后卵母细胞发育正常，但受精后的胚胎发育迟缓，且大部分在发育过程中停滞或凋亡，最终导致生育能力显著下降。研究发现，PIWI蛋白功能存在明确的分工但又紧密联系。在卵母细胞发育中，PIWIL1/piRNA可以代偿PIWIL3/piRNA活性，抑制以LINE/L1和LTR/ERVK为主的活跃转座子的表达，反之则不然。而在生精细胞发育过程中，PIWIL4入核功能及其相关piRNA的加工依赖于PIWIL2，两者协同完成转座子的转录水平和转录后水平沉默。综上，本研究使用更具代表性的金黄地鼠作为模型，全面绘制了PIWI家族各个成员在配子发生和早期胚胎发育中的时空表达谱，构建并比较了四种PIWI突变体的生育表型和分子表型，发现了四种PIWI蛋白在配子发生和早期胚胎发育中具有非冗余的调控作用，为piRNA通路异常与人类生殖相关疾病的诊治奠定了重要理论基础、提供了动物模型。研究工作得到国家自然科学基金委员会、科学技术部、中国科学院、上海市和江苏省的资助。研究工作获得分子细胞卓越中心实验动物技术平台和信息化管理团队的支持。南京医科大学科研人员参与研究。