Piwi-interacting RNAs (piRNAs) and Colorectal Carcinoma: Emerging Non-invasive diagnostic Biomarkers with Potential Therapeutic Target Based Clinical Implications

Abstract: PIWI-interacting RNAs (piRNAs) constitute new small non-coding RNA molecules of around 24-31 nucleotides in length, mostly performing regulatory roles for the piwi protein family members. In recent times, developing evidence proposes that piRNAs are expressed in a tissue-specific way in various human tissues and act as moderate vital signalling pathways at the transcriptional or post-transcriptional level in addition to mammalian germline. Recent findings, however, show that the unusual expression of piRNAs is an exclusive and discrete feature in several diseases, including many human cancers. Recently, considerable evidence indicates that piRNAs could be dysregulated thus playing critical roles in tumorigenesis. The function and underlying mechanisms of piRNAs in cancer, particularly in colorectal carcinoma, are not fully understood to date. Abnormal expression of piRNAs is emerging as a critical player in cancer cell proliferation, apoptosis, invasion, and migration in vitro and in vivo. Functionally, piRNAs preserve genomic integrity and regulate the expression of downstream target genes through transcriptional or post-transcriptional mechanisms by repressing transposable elements' mobilization. However, little research has been done to check Piwi and piRNAs' potential role in cancer and preserve genome integrity by epigenetically silencing transposons via DNA methylation, especially in germline cancer stem cells. This review reveals emerging insights into piRNA functions in colorectal carcinoma, revealing novel findings behind various piRNA-mediated gene regulation mechanisms, biogenetic piRNA processes, and possible applications of piRNAs and piwi proteins in cancer diagnosis and their potential clinical significance in the treatment of colorectal carcinoma patients.