Critical Roles of PIWIL1 in Human Tumors: Expression, Functions, Mechanisms, and Potential Clinical Implications.

Peixin Dong,Kei Ihira,Daozhi Xu,Junming Yue,Hidemichi Watari,Noriko Kobayashi,Yosuke Konno,Ying Xiong

doi:10.3389/fcell.2021.656993

Abstract

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a class of small non-coding RNA molecules that are 24–31 nucleotides in length. PiRNAs are thought to bind to PIWI proteins (PIWL1-4, a subfamily of Argonaute proteins), forming piRNA/PIWI complexes that influence gene expression at the transcriptional or post-transcriptional levels. However, it has been recently reported that the interaction of PIWI proteins with piRNAs does not encompass the entire function of PIWI proteins in human tumor cells. PIWIL1 (also called HIWI) is specifically expressed in the testis but not in other normal tissues. In tumor tissues, PIWIL1 is frequently overexpressed in tumor tissues compared with normal tissues. Its high expression is closely correlated with adverse clinicopathological features and shorter patient survival. Upregulation of PIWIL1 drastically induces tumor cell proliferation, epithelial-mesenchymal transition (EMT), invasion, cancer stem-like properties, tumorigenesis, metastasis and chemoresistance, probably via piRNA-independent mechanisms. In this article, we summarize the current existing literature on PIWIL1 in human tumors, including its expression, biological functions and regulatory mechanisms, providing new insights into how the dysregulation of PIWIL1 contributes to tumor initiation, development and chemoresistance through diverse signaling pathways. We also discuss the most recent findings on the potential clinical applications of PIWIL1 in cancer diagnosis and treatment.

Highlights

P-element-induced wimpy testis (PIWI)-interacting RNAs are small (24–31 nucleotides), single-stranded non-coding RNAs with 2 -O-methylated at their 3 ends (Ng et al, 2016; Wang et al, 2019; Yu et al, 2019)
Amplifications are more frequent in diffuse glioma, sarcoma, 1https://www.oncomine.org 2https://www.cbioportal.org pheochromocytoma, ovarian cancer, bladder cancer, cervical cancer, esophageal squamous cell carcinoma, and renal non-clear cell carcinoma (Figure 1B). These results suggest that PIWIL1 dysregulation is frequently occurring in human tumor tissues and PIWIL1 might serve as a novel biomarker in several malignancies
An induced expression of PIWIL1 has been linked to lymph node metastasis in patients with gastric cancer (Wang et al, 2012; Gao et al, 2018), colon cancer (Sun et al, 2017), hepatocellular carcinoma (Jiang et al, 2011; Zhao et al, 2012), breast cancer (Wang D.W. et al, 2014), bladder cancer (Eckstein et al, 2018), renal cell carcinoma (Stöhr et al, 2019), and endometrial cancer (Chen et al, 2015a). These findings demonstrate that high PIWIL1 expression might be considered as a useful marker for an aggressive phenotype of several malignancies

Summary

Introduction

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are small (24–31 nucleotides), single-stranded non-coding RNAs with 2 -O-methylated at their 3 ends (Ng et al, 2016; Wang et al, 2019; Yu et al, 2019).

Results

Conclusion