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Ovarian cancer (OC) is one of the most lethal gynecological malignancies, yet molecular mechanisms underlying its origin and progression remain poorly understood. With increasing reports of piRNA pathway deregulation in various cancers, we aimed to better understand its role in OC through a comprehensive analysis of key genes: , , , , , , and mutants of () and (). High-throughput qRT-PCR ( = 45) and CSIOVDB ( = 3431) showed differential gene expression when comparing benign ovarian tumors, low grade OC and high grade serous OC (HGSOC). Significant correlation of disparate piRNA pathway gene expression levels with better progression free, post-progression free and overall survival suggests a complex role of this pathway in OC. We discovered expression in chemosensitive but not chemoresistant primary HGSOC cells, providing a potential target against chemoresistant disease. As a first, we revealed that follicle stimulating hormone increased expression in OV-90 cells. , , , and overexpression in vitro and in vivo decreased motility and invasion of OVCAR-3 and OV-90 cells. Interestingly, and , induced increased motility and invasion compared to and . Our results in HGSOC highlight the intricate role piRNA pathway genes play in the development of malignant neoplasms.
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http://dx.doi.org/10.3390/cancers13010004 | DOI Listing |
Mol Cell
September 2025
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria. Electronic address:
PIWI-clade Argonaute proteins and their associated PIWI-interacting RNAs (piRNAs) are essential guardians of genome integrity, silencing transposable elements through distinct nuclear and cytoplasmic pathways. Nuclear PIWI proteins direct heterochromatin formation at transposon loci, while cytoplasmic PIWIs cleave transposon transcripts to initiate piRNA amplification. Both processes rely on target RNA recognition by PIWI-piRNA complexes, yet how this leads to effector recruitment is unclear.
View Article and Find Full Text PDFMethods Mol Biol
August 2025
Deparment of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
The PIWI-interacting RNA (piRNA) pathway plays a crucial role in the defense of metazoan genomes against parasitic transposable elements. The major source of piRNAs in the model organism Drosophila melanogaster is defective transposon copies located in piRNA clusters-genomic regions with a high piRNA density that are thought to serve as an immunological memory of past invasions by those elements. Different approaches have been used to annotate piRNA clusters in model organisms such as flies, mice, and rats, and software such as proTRAC or piClust are available for piRNA cluster annotation.
View Article and Find Full Text PDFBiol Open
September 2025
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Reactivation of transposable elements (TEs) in somatic tissues, particularly of LINE-1, is associated with disease by causing gene mutations and DNA damage. Previous work has shown that the PIWI pathway is crucial for TE suppression in the germline. However, the status and function of this pathway is not well characterized in differentiated somatic cells and there is a lack of consensus on the role of the pathway in somatic tumorigenesis.
View Article and Find Full Text PDFCancer Rep (Hoboken)
August 2025
Department of Experimental Research, South China Hospital, Medical School, Shenzhen University, Shenzhen, China.
Piwi-interacting RNA (piRNA) represents a class of small non-coding RNA molecules, typically ranging in length from 18 to 35 nucleotides. These molecules are critically involved in the preservation of genomic integrity and the regulation of protein translation processes. Recently, emerging scholarly research indicates that piRNA exhibits tissue-specific expression profiles within a variety of human malignancies, where they intricately regulate key signaling pathways at both the transcriptional and post-transcriptional levels.
View Article and Find Full Text PDFAsian Pac J Cancer Prev
July 2025
Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt.
Background: Bladder cancer (BC) remains one of the most prevalent and recurrent malignancies worldwide. Identification of early biomarkers and prognostic indicators is vital for improving diagnostic accuracy and therapeutic outcomes. PIWI-interacting RNA pathway proteins (PIWILs), known regulators of gene silencing and genome stability, have emerged as potential biomarkers in various cancers.
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