The Emerging Role of PIWI-Interacting RNAs (piRNAs) in Gastrointestinal Cancers: An Updated Perspective

Abstract

Gastrointestinal (GI) cancers produce ~3.4 million related deaths worldwide, comprising 35% of all cancer-related deaths. The high mortality among GI cancers is due to late diagnosis, the presence of metastasis and drug resistance development. Additionally, current clinical markers do not adequately guide patient management, thereby new and more reliable biomarkers and therapeutic targets are still needed for these diseases. RNA-seq technology has allowed the discovery of new types of RNA transcripts including PIWI-interacting RNAs (piRNAs), which have particular characteristics that enable these molecules to act via diverse molecular mechanisms for regulating gene expression. Cumulative evidence has described the potential role of piRNAs in the development of several tumor types as a likely explanation for certain genomic abnormalities and signaling pathways’ deregulations observed in cancer. In addition, these piRNAs might be also proposed as promising diagnostic or prognostic biomarkers or as potential therapeutic targets in malignancies. This review describes important topics about piRNAs including their molecular characteristics, biosynthesis processes, gene expression silencing mechanisms, and the manner in which these transcripts have been studied in samples and cell lines of GI cancers to elucidate their implications in these diseases. Moreover, this article discusses the potential clinical usefulness of piRNAs as biomarkers and therapeutic targets in GI cancers.

Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications

“…PiRNAs are a novel class of short chain ncRNAs (26-30 nucleotides) involved in a wide variety of physiological and pathological processes. They can regulate the expression of somatic genes through various mechanisms, including DNA methylation, chromatin modification and transposon silencing ( 229 , 230 ). An increasing amount of evidence suggests that piRNAs are key regulators in the development of cancer drug resistance ( 231 – 233 ).…”

Exosomal Non-Coding RNAs: New Insights into the Biology of Hepatocellular Carcinoma

“…RNAs are divided into coding RNAs (mRNAs) and non-coding RNAs based on whether they can encode proteins. Studies have shown that mRNAs account for less than 2% of the total genome, and more than 98% are ncRNAs, such as lncRNAs, miRNAs, circRNAs, small nucleolar RNAs (snoRNAs) [ 35 ], tRNA-derived small RNAs [ 36 ], and piwi-interacting RNAs [ 37 , 38 ]. At a time when ncRNAs were poorly understood, they were considered nonfunctional “junk” [ 39 ].…”

“…Except for the exosomal miRNAs, lncRNAs and circRNAs, some other ncRNAs, including tRNA-derived small RNAs [ 36 ] and piwi-interacting RNAs [ 37 , 38 ], also participate in tumorigenesis. Due to the lack of adequate literature, we do not make too much of an elaboration here.…”

Noncoding RNAs Emerging as Drugs or Drug Targets: Their Chemical Modification, Bio-Conjugation and Intracellular Regulation

“…On the other hand, aberrantly expressed ncRNAs are closely related with the pathogenesis of various diseases such as cancers. Under complex cancer conditions, the deregulation or dysfunction of ncRNAs has been reported to affect multiple cellular processes in almost all major cancers [ 4 , 5 , 6 , 7 ]. The roles of cancer-involved ncRNAs such as miRNA, lncRNA and circRNA have been extensively studied, and their potential mechanisms in cancer development are progressively being established [ 8 , 9 ].…”