4.7 Review

The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers

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Review Cell Biology

Emerging roles and functional mechanisms of PIWI-interacting RNAs

Xin Wang et al.

Summary: PIWI-interacting RNAs (piRNAs) are important small non-coding RNAs that play crucial roles in germ line development through silencing transposable elements and regulating protein-coding genes. Recent studies have advanced our understanding of piRNA biogenesis and function, and highlighted their significance in human infertility, cancer, and neurological diseases.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2023)

Article Cell Biology

piRNAs initiate transcriptional silencing of spermatogenic genes during C. elegans germline development

Eric Cornes et al.

Summary: Our study identifies piRNAs as direct regulators of endogenous transcriptional programs during germline development and gamete differentiation in C. elegans, triggering the transcriptional silencing of hundreds of spermatogenic genes and promoting sperm differentiation and function. This silencing signal requires piRNA-dependent small RNA biogenesis and loading into downstream nuclear effectors.

DEVELOPMENTAL CELL (2022)

Article Gastroenterology & Hepatology

N6-Methyladenosine Reader YTHDF1 Promotes ARHGEF2 Translation and RhoA Signaling in Colorectal Cancer

Shiyan Wang et al.

Summary: The study identified a novel oncogenic epitranscriptome axis of YTHDF1-m(6)A-ARHGEF2 that regulates CRC tumorigenesis and metastasis.

GASTROENTEROLOGY (2022)

Review Genetics & Heredity

Disorders and roles of tsRNA, snoRNA, snRNA and piRNA in cancer

Lin Xiao et al.

Summary: Non-coding RNAs play important roles in regulatory functions, and the emergence of high-throughput sequencing technology has expanded our understanding of them. The abnormal expression of tsRNA, snoRNA, snRNA, and piRNA is closely related to the progression of cancer, and these RNAs play important roles in various biological processes.

JOURNAL OF MEDICAL GENETICS (2022)

Article Medicine, Research & Experimental

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

Qi Xie et al.

Summary: This study reveals that piRNA-14633 is highly expressed in cervical cancer tissues and cells, and promotes the proliferation, migration, and invasion of cervical cancer cells through the METTL14/CYP1B1 signaling axis. These findings highlight the important role of piRNA-14633 in cervical cancer.

JOURNAL OF TRANSLATIONAL MEDICINE (2022)

Article Cell Biology

Paramecium Polycomb repressive complex 2 physically interacts with the small RNA-binding PIWI protein to repress transposable elements

Caridad Miro-Pina et al.

Summary: Polycomb repressive complex 2 (PRC2) is involved in maintaining transcriptional silence and silencing transposable elements (TEs) through deposition of specific histone marks. This study identified the core complex and cofactors of PRC2 in Paramecium, and revealed the importance of RNA interference (RNAi) pathway in targeting histone marks to TEs.

DEVELOPMENTAL CELL (2022)

Review Oncology

LncRNA-mediated DNA methylation: an emerging mechanism in cancer and beyond

Wanxu Huang et al.

Summary: DNA methylation is a crucial epigenetic mechanism that regulates gene expression, and aberrant patterns of DNA methylation are associated with human diseases such as cancer. This review provides an overview of the current understanding of long non-coding RNA (lncRNA)-mediated DNA methylation, with a focus on its roles in cancer. The potential clinical applications of this mechanism in RNA-targeting drug development are also discussed.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2022)

Article Biochemistry & Molecular Biology

Identification of piRNA disease associations using deep learning

Syed Danish Ali et al.

Summary: piRNAs play a crucial role in maintaining genome integrity, and piRDA is an effective deep learning method for identifying piRNA-disease associations, facilitating drug development.

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2022)

Review Biochemistry & Molecular Biology

The regulatory function of piRNA/PIWI complex in cancer and other human diseases: The role of DNA methylation

Dong-Dong Jia et al.

Summary: This review summarizes the DNA methylation regulation mechanisms mediated by piRNA/PIWI proteins and the methylation changes caused by piRNA/PIWI proteins in different diseases, especially cancers. Dysregulation of piRNAs may contribute to disease occurrence through epigenetic changes such as DNA methylation and chromatin modification. Furthermore, piRNAs have potential clinical applications as novel biomarkers for cancer diagnosis, and the methylation changes associated with piRNA/PIWI proteins are of significant importance in treatment.

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES (2022)

Article Hematology

piRNA-30473 contributes to tumorigenesis and poor prognosis by regulating m6A RNA methylation in DLBCL

Huiying Han et al.

Summary: The study demonstrates that piRNA-30473 plays an oncogenic role in promoting the aggressive phenotype of DLBCL, and its depletion can reduce proliferation and induce cell cycle arrest. Through regulating m6A RNA methylation, the piRNA-30473/WTAP/HK2 axis contributes to the progression of DLBCL.
Article Cell Biology

Piwil1 Regulates Glioma Stem Cell Maintenance and Glioblastoma Progression

Haidong Huang et al.

Summary: The Piwi-like family members are overexpressed in glioblastoma, with Piwil1 being the most frequently overexpressed. Piwil1 is enriched in glioma stem-like cells to maintain self-renewal, and its knockdown leads to changes in gene expression and cell cycle arrest, senescence, or apoptosis. Piwil1 regulates the mRNA stability of key genes involved in cancer stem cell maintenance, and its knockdown suppresses tumor growth and promotes survival in animal models of glioblastoma.

CELL REPORTS (2021)

Review Biochemistry & Molecular Biology

The Role of H3K4 Trimethylation in CpG Islands Hypermethylation in Cancer

Giuseppe Zardo

Summary: CpG methylation plays vital roles in gene regulation, with CpG islands in promoters remaining unmethylated throughout mammalian embryogenesis and development. Understanding the mechanisms and effects of aberrant CpG island hypermethylation in tumors requires further investigation.

BIOMOLECULES (2021)

Article Biochemistry & Molecular Biology

Terminal modification, sequence, length, and PIWI-protein identity determine piRNA stability

Ildar Gainetdinov et al.

Summary: The stability of mouse piRNAs is influenced by trimming and methylation, with multiple mechanisms involved in the degradation of unmethylated piRNAs. Unlike miRNAs, piRNAs in flies and mice are protected by 3' terminal 2'-O-methylation from complementarity-dependent degradation, while pre-piRNA trimming protects mouse piRNAs from degradation pathways unrelated to trigger complementarity.

MOLECULAR CELL (2021)

Article Multidisciplinary Sciences

Germ granule dysfunction is a hallmark and mirror of Piwi mutant sterility

Maya Spichal et al.

Summary: The sterility of the C. elegans Piwi prg-1 mutant is not associated with transposon-induced DNA damage, but is instead associated with and phenocopied by dysfunction of germ granules.

NATURE COMMUNICATIONS (2021)

Review Microbiology

Mammalian antiviral systems directed by small RNA

Tomoko Takahashi et al.

Summary: Viruses are widespread and organisms have evolved various immune systems to limit virus replication. While protein-guided immune systems in mammals are well studied, small RNA-directed immune systems also play important roles in certain contexts, indicating their continued activity in mammalian antiviral immunity.

PLOS PATHOGENS (2021)

Article Cell Biology

piRNA-823 Is Involved in Cancer Stem Cell Regulation Through Altering DNA Methylation in Association With Luminal Breast Cancer

Xin Ding et al.

Summary: piR-823 is upregulated in luminal breast cancer cells, particularly in CSCs. It plays an oncogenic role in regulating cell proliferation and colony formation, promoting stemness in breast cancer CSCs. Inhibition of piR-823 significantly inhibits tumor growth in mammary glands.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

Article Cell Biology

Piwi-interacting RNA-651 promotes cell proliferation and migration and inhibits apoptosis in breast cancer by facilitating DNMT1-mediated PTEN promoter methylation

Ting Liu et al.

Summary: piR-651 is highly expressed in breast cancer tissues and cell lines, promoting proliferation and migration of cancer cells by facilitating DNMT1-mediated PTEN promoter methylation, inducing apoptosis.

CELL CYCLE (2021)

Article Biochemistry & Molecular Biology

Large Drosophila germline piRNA clusters are evolutionarily labile and dispensable for transposon regulation

Daniel Gebert et al.

Summary: Through synteny analysis, it was shown that large clusters are evolutionarily labile and mostly species-specific across the Drosophila genus, arising at loci characterized by recurrent chromosomal rearrangements. Chromosomal deletions in D. melanogaster demonstrated that the three largest germline clusters, accounting for the accumulation of >40% of all transposon-targeting piRNAs in ovaries, are not required for fertility nor for transposon regulation in trans. Evidence suggests that dispersed elements may play a central role in transposon defense rather than the regulatory action of large Drosophila germline clusters in trans.

MOLECULAR CELL (2021)

Article Cell Biology

pre-piRNA trimming and 2′-O-methylation protect piRNAs from 3′ tailing and degradation in C. elegans

Benjamin Pastore et al.

Summary: The study found that the 3' termini of Caenorhabditis elegans piRNAs undergo nontemplated nucleotide addition, leading to extensive base-pairing interaction with their target RNAs. Both PARN-1 and HENN-1 enzymes collaboratively protect piRNAs from tailing and degradation through pre-piRNA trimming and 2'-O-methylation.

CELL REPORTS (2021)

Article Biochemistry & Molecular Biology

Argonaute (AGO) proteins play an essential role in mediating BMP9-induced osteogenic signaling in mesenchymal stem cells (MSCs)

Yukun Mao et al.

Summary: The study shows that BMP9 can induce osteogenic and adipogenic differentiation of MSCs by upregulating the expression of AGO proteins. Silencing individual AGO expression leads to a decrease in osteogenic marker activity, while silencing all four AGO genes significantly diminishes BMP9-induced differentiation and bone formation of MSCs. AGO proteins and small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs.

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PIWI-interacting RNAs: Mitochondria-based biogenesis and functions in cancer

Jing-Fen Su et al.

Summary: piRNAs play essential roles not only in germlines but also in somatic and cancerous tissues. They are involved in biogenesis through ping-pong cycle initiation and mitochondria-based phased production, and contribute to carcinogenesis by participating in DNA methylation, histone marker deposition, mRNA degradation, and protein modification.

GENES & DISEASES (2021)

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Regulatory Mechanism of MicroRNA Expression in Cancer

Zainab Ali Syeda et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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DNA Modification Readers and Writers and Their Interplay

Cathia Rausch et al.

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Zucchini consensus motifs determine the mechanism of pre-piRNA production

Natsuko Izumi et al.

NATURE (2020)

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The piRNA pathway in Drosophila ovarian germ and somatic cells

Kaoru Sato et al.

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MUC1-C regulates lineage plasticity driving progression to neuroendocrine prostate cancer (vol 11, 338, 2020)

Yota Yasumizu et al.

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Crystal structure of Drosophila Piwi

Sonomi Yamaguchi et al.

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The Biogenesis and Functions of piRNAs in Human Diseases

Xi Wu et al.

MOLECULAR THERAPY-NUCLEIC ACIDS (2020)

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Mechanistic insights into m6A modification of U6 snRNA by human METTL16

Tomohiko Aoyama et al.

NUCLEIC ACIDS RESEARCH (2020)

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SPOCD1 is an essential executor of piRNA-directed de novo DNA methylation

Ansgar Zoch et al.

NATURE (2020)

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PIWIL1 promotes gastric cancer via a piRNA-independent mechanism

Shuo Shi et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation

Charlie Y. Shi et al.

SCIENCE (2020)

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The RNA-Binding ATPase, Armitage, Couples piRNA Amplification in Nuage to Phased piRNA Production on Mitochondria

Daniel Tianfang Ge et al.

MOLECULAR CELL (2019)

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Aberrant expression of select piRNA-pathway genes does not reactivate piRNA silencing in cancer cells

Pavol Genzor et al.

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The emerging role of the piRNA/piwi complex in cancer

Yongmei Liu et al.

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Piwi-interacting RNAs (piRNAs) and cancer: Emerging biological concepts and potential clinical implications

Wenhao Weng et al.

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PIWI-interacting RNAs: small RNAs with big functions

Deniz M. Ozata et al.

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Cancer-Germline Antigen Expression Discriminates Clinical Outcome to CTLA-4 Blockade

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PNLDC1, mouse pre-piRNA Trimmer, is required for meiotic and post-meiotic male germ cell development

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Zc3h13 Regulates Nuclear RNA m6A Methylation and Mouse Embryonic Stem Cell Self-Renewal

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piRNA-Guided Genome Defense: From Biogenesis to Silencing

Benjamin Czech et al.

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Dynamic DNA methylation: In the right place at the right time

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piR-651 and its function in 95-D lung cancer cells

Jie Yao et al.

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PIWI-Interacting RNA: Its Biogenesis and Functions

Yuka W. Iwasaki et al.

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Identification of novel piRNAs in bladder cancer

Haiyan Chu et al.

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MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes

Peng Zhang et al.

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Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

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Profiling of the small RNA populations in human testicular germ cell tumors shows global loss of piRNAs

T. B. Rounge et al.

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Slicing and Binding by Ago3 or Aub Trigger Piwi-Bound piRNA Production by Distinct Mechanisms

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A piRNA-like small RNA interacts with and modulates p-ERM proteins in human somatic cells

Yuping Mei et al.

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TET proteins and 5-methylcytosine oxidation in hematological cancers

Myunggon Ko et al.

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Epigenetic loss of the PIWI/piRNA machinery in human testicular tumorigenesis

Humberto J. Ferreira et al.

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Novel dimensions of piRNAs in cancer

Yuping Mei et al.

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piRNA-Triggered MIWI Ubiquitination and Removal by APC/C in Late Spermatogenesis

Shuang Zhao et al.

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DNA Methylation and Its Basic Function

Lisa D. Moore et al.

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piRNAs and their involvement in male germline development in mice

Ramesh S. Pillai et al.

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Structure and function of Zucchini endoribonuclease in piRNA biogenesis

Hiroshi Nishimasu et al.

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The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis

Jonathan J. Ipsaro et al.

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Concise Review: The Piwi-piRNA Axis: Pivotal Beyond Transposon Silencing

Shiva Bamezai et al.

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De novo DNA methylation: a germ cell perspective

Sebastien A. Smallwood et al.

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Cinzia Puppin et al.

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The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements

Serena De Fazio et al.

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N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO

Guifang Jia et al.

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A decade of exploring the cancer epigenome - biological and translational implications

Stephen B. Baylin et al.

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Somatic piRNA biogenesis

Phillip D. Zamore

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CpG oligonucleotides for immunotherapeutic treatment of neuroblastoma

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The Biogenesis and Function of PIWI Proteins and piRNAs: Progress and Prospect

Travis Thomson et al.

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A Broadly Conserved Pathway Generates 3′UTR-Directed Primary piRNAs

Nicolas Robine et al.

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Biogenesis of small RNAs in animals

V. Narry Kim et al.

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Biogenesis and germline functions of piRNAs

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The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race

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A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in zebrafish

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A slicer-mediated mechanism for repeat-associated siRNA 5′ end formation in Drosophila

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A distinct small RNA pathway silences selfish genetic elements in the germline

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A germline-specific class of small RNAs binds mammalian Piwi proteins

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