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Although diagnostics and therapies have progressed, the molecular drivers of initiation and progression remain incompletely defined. High-throughput sequencing has highlighted small non-coding RNAs in gene regulation and genomic stability. This review focuses on PIWI-interacting RNAs (piRNAs), which can act as tumor suppressors or oncogenes via post-transcriptional silencing, epigenetic changes, and pathway modulation, with dysregulation linked to cancer hallmarks and clinical biomarker potential.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/regulatory-mechanisms-and-clinical-implications-of-piwi-interacting-rnas-pirnas-in-major-digestive-tract-cancers/372493/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/regulatory-mechanisms-and-clinical-implications-of-piwi-interacting-rnas-pirnas-in-major-digestive-tract-cancers/372493.png","ImageObject",300,407,{"name":92,"@type":93},"Aditya","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main clinical focus of the review?","Question",{"text":113,"@type":114},"The review summarizes how piRNAs regulate major digestive tract cancers and how their dysregulation relates to tumor development, progression, and clinical outcomes.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How can piRNAs influence digestive tract cancers?",{"text":118,"@type":114},"piRNAs exert effects through post-transcriptional gene silencing, epigenetic modifications, and modulation of tumor-related signaling pathways such as Wnt/β-catenin, PI3K/Akt, and MAPK.",{"name":120,"@type":111,"acceptedAnswer":121},"Why are piRNAs considered promising biomarkers or therapeutic targets?",{"text":122,"@type":114},"Distinct piRNA expression profiles correlate with clinical features and outcomes, and therapies targeting dysregulated piRNAs or downstream effectors may support precision medicine approaches.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},372493,1790636020,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},962085564549,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Li etal. Cancer Cell International (2025) 25:244 Cancer Cell International  \n[https://doi.org/10.1186/s12935-025-03889-6](https://doi.org/10.1186/s12935-025-03889-6)  \nREVIEW Open Access  \nRegulatory mechanisms and clinical   \nimplications of PIWI-interacting RNAs (piRNAs) in major digestive tract cancers  \nPenghui Li 1, Yuan Xue2 and Xinyu Gu3*  \nAbstract  \nCancers of the digestive tract, including those affecting the esophagus, stomach, liver, pancreas, and colorectum, impose a substantial global health burden due to their high morbidity and mortality rates. Despite advancementsin diagnostic and treatment modalities, the molecular mechanisms underpinning the initiation and progression of digestive tract cancers remain incompletely understood. Recent progress in high-throughput sequencing technology has uncovered the crucial role of small non-coding RNAs (ncRNAs) in regulating gene expression and maintaining genomic stability across various cancers, including those affecting the digestive tract. P-elementinduced wimpy testis (PIWI)-integrating RNAs (piRNAs), a subset of small ncRNAs, emerge as pivotal regulators in preserving genome integrity by suppressing transposable elements in germline cells. Growing evidence implicates piRNAs in the development and advancement of digestive tract cancers. Notably, piRNAs exhibit complex and multifaceted roles in these tumors, functioning as both tumor suppressors and oncogenes. They exert their effects through diverse mechanisms, including post-transcriptional gene silencing, epigenetic modifications, and modulation of signaling pathways involved in tumorigenesis, such as the Wnt/β-catenin, PI3K/Akt, and MAPK pathways. Dysregulation of piRNAs disrupts key cellular processes, including cell cycle regulation, apoptosis, epithelial-mesenchymal transition, and metastasis, across various digestive tract cancers. Moreover, distinct expression profiles of specific piRNAs correlate with diverse clinical features and outcomes in individuals afflicted with digestive tract cancers, highlighting their potential as diagnostic and prognostic biomarkers in this context. Furthermore, therapeutic interventions targeting dysregulated piRNAs or their downstream effectors hold promise as novel avenues for precision medicine approaches in managing digestive tract cancers. In this review, we summarize the current understanding of piRNAs in digestive tract cancers, focusing on their dual roles as both tumor suppressors and oncogenes. We further delve into the intricate molecular mechanisms by which piRNAs modulate crucial cellular processes implicated in tumorigenesis. Additionally, we explore the potential of piRNAsas valuable diagnostic, prognostic, and therapeutic biomarkers in the landscape of digestive tract cancers. By elucidating the complex interplay between piRNAs and digestive tract cancers, this review aims to offer insights into novel therapeutic strategies centered around targeting piRNAs for precision medicine approaches in the management of these malignancies.  \n*Correspondence: Xinyu Gu [hkdguxy@163.com](hkdguxy@163.com)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use i","cbCaitsE3VPhlB2U","https://ap.wps.com/l/cbCaitsE3VPhlB2U","pdf",1796942,14,"English","# Abstract\n# Introduction\n# Regulatory mechanisms and clinical implications\n## Dual roles of piRNAs\n## Key signaling pathways and cellular processes\n## Diagnostic, prognostic, and therapeutic biomarkers","[{\"question\":\"What is the main clinical focus of the review?\",\"answer\":\"The review summarizes how piRNAs regulate major digestive tract cancers and how their dysregulation relates to tumor development, progression, and clinical outcomes.\"},{\"question\":\"How can piRNAs influence digestive tract cancers?\",\"answer\":\"piRNAs exert effects through post-transcriptional gene silencing, epigenetic modifications, and modulation of tumor-related signaling pathways such as Wnt/β-catenin, PI3K/Akt, and MAPK.\"},{\"question\":\"Why are piRNAs considered promising biomarkers or therapeutic targets?\",\"answer\":\"Distinct piRNA expression profiles correlate with clinical features and outcomes, and therapies targeting dysregulated piRNAs or downstream effectors may support precision medicine approaches.\"}]","Regulatory mechanisms and clinical implications of PIWI-interacting RNAs (piRNAs) in major digestive tract cancers | PDF",1790194656,35]