Piwil1 Regulates Glioma Stem Cell Maintenance and Glioblastoma Progression

Huang, Haidong; Yu, Xingjiang; Han, Xiangzi; Hao, Jing; Zhao, Jianjun; Bebek, Gürkan; Bao, Shideng; Prayson, Richard A.; Khalil, Ahmad M.; Jankowsky, Eckhard; Yu, Jennifer

doi:10.1016/j.celrep.2020.108522

Cited by 47 publications

(30 citation statements)

References 53 publications

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“…This study also suggested that the pro-cancer stem cell activities of PIWIL1 might be mediated by the induction of two stem cellrelated genes (CD44 and ALDH1) (Chen et al, 2015a). Recently, it was shown that PIWIL1 is enriched in glioma stem-like cells (GSCs) and silencing PIWIL1 in GSCs impaired their selfrenewal and triggered senescence or apoptosis (Huang et al, 2021). PIWIL1 knockdown strongly increased the expression of BTG2 and FBXW7, but reduced the levels of c-MYC, Olig2 and Nestin in GSCs (Huang et al, 2021).…”

Section: Regulation Of Emt Cancer Stem Cell-like Properties and Drugmentioning

confidence: 80%

“…Recently, it was shown that PIWIL1 is enriched in glioma stem-like cells (GSCs) and silencing PIWIL1 in GSCs impaired their selfrenewal and triggered senescence or apoptosis (Huang et al, 2021). PIWIL1 knockdown strongly increased the expression of BTG2 and FBXW7, but reduced the levels of c-MYC, Olig2 and Nestin in GSCs (Huang et al, 2021). These results supported that PIWIL1 is important for multiple aspects of tumor biology, including EMT-driven metastatic growth, the maintenance of cancer stem cell-like phenotypes, and resistance to therapeutic agents.…”

Section: Regulation Of Emt Cancer Stem Cell-like Properties and Drugmentioning

confidence: 99%

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

Dong

Xiong

Konno

et al. 2021

Front. Cell Dev. Biol.

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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.

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Section: Regulation Of Emt Cancer Stem Cell-like Properties and Drugmentioning

confidence: 80%

Section: Regulation Of Emt Cancer Stem Cell-like Properties and Drugmentioning

confidence: 99%

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

Dong

Xiong

Konno

et al. 2021

Front. Cell Dev. Biol.

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“…Consistent with these findings, miR-422a was reported to directly target SKP2 [ 25 ], which is an E3 ubiquitin ligase and was confirmed to promote fibroblast proliferation in pulmonary fibrosis through via ubiquitin–proteasome pathway [ 26 ]. In addition, miR-2116-3p was shown to interact with and inhibit PIWIL1 [ 27 ], and silencing of PIWIL1 was reported to upregulate FBXW7 [ 28 ], which is a component of E3 ubiquitin-protein ligase complex and was observed to induce expression of fibrotic genes including fibronectin during pulmonary fibrosis [ 29 ]. Also, miR-3187-3p was confirmed to target ASXL1 [ 30 ], a histone H2A deubiquitinase [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and functional analysis of a three-miRNA ceRNA network in hypertrophic scars

et al. 2021

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Background Hypertrophic scar (HTS) is a fibrotic disorder of skins and may have repercussions on the appearance as well as functions of patients. Recent studies related have shown that competitive endogenous RNA (ceRNA) networks centering around miRNAs may play an influential role in HTS formation. This study aimed to construct and validate a three-miRNA (miR-422a, miR-2116-3p, and miR-3187-3p) ceRNA network, and explore its potential functions. Methods Quantitative real‑time PCR (qRT‑PCR) was used to compare expression levels of miRNAs, lncRNAs, and genes between HTS and normal skin. Target lncRNAs and genes of each miRNA were predicted using starBase as well as TargetScan database to construct a distinct ceRNA network; overlapping target lncRNAs and genes of the three miRNAs were utilized to develop a three-miRNA ceRNA network. For every network, protein–protein interaction (PPI) network analysis was performed to identify its hub genes. For each network and its hub genes, Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to explore their possible functions. Results MiR-422a, miR-2116-3p, and miR-3187-3p were all downregulated in HTS tissues and fibroblasts. MiR-422a-based ceRNA network consisted of 101 lncRNAs with 133 genes; miR-2116-3p-centered ceRNA network comprised 85 lncRNAs and 978 genes; miR-3187-3p-derived ceRNA network encompassed 84 lncRNAs as well as 1128 genes. The three-miRNA ceRNA network included 2 lncRNAs with 9 genes, where MAPK1, FOSL2, ABI2, KPNA6, CBL, lncRNA-KCNQ1OT1, and lncRNA-EBLN3P were upregulated. According to GO and KEGG analysis, these networks were consistently related to ubiquitination. Three ubiquitination-related genes (CBL, SMURF2, and USP4) were upregulated and negatively correlated with the expression levels of the three miRNAs in HTS tissues. Conclusions This study identified a three-miRNA ceRNA network, which might take part in HTS formation and correlate with ubiquitination.

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“…In fact, defects on PDHX caused pyruvate dehydrogenase deficiency, resulting in lactic acidosis and neurological dysfunction in infancy and early childhood [ 26 ]. PIWIL1 gene encodes a member of the PIWI subfamily of Argonaute proteins with conserved regions such as PAZ and Piwi motifs functioning in translational regulation including RNA silencing and self-renewal of germline and hematopoietic stem cells in human [ 27 ]. For these reasons, down-regulation of PIWIL1 could affect our body to have a variety of problems including abnormal production of many blood cells.…”

Section: Discussionmentioning

confidence: 99%

Childhood Obesity-Related Mechanisms: MicroRNome and Transcriptome Changes in a Nested Case-Control Study

Kim

Lim

et al. 2021

Biomedicines

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Childhood obesity could contribute to adulthood obesity, leading to adverse health outcomes in adults. However, the mechanisms for how obesity is developed are still unclear. To determine the epigenome-wide and genome-wide expression changes related with childhood obesity, we compared microRNome and transcriptome levels as well as leptin protein levels in whole bloods of 12 obese and 24 normal children aged 6 years. miR-328-3p, miR-1301-3p, miR-4685-3p, and miR-6803-3p were negatively associated with all obesity indicators. The four miRNAs were also associated with 3948 mRNAs, and separate 475 mRNAs (185 among 3948 mRNAs) were associated with all obesity indicators. The 2533 mRNAs (64.2%) among the 3948 mRNAs and 286 mRNAs (60.2%) among the 475 mRNAs were confirmed as targets of the four miRNAs in public databases through miRWalk 2.0. Leptin protein was associated with miR-6803-3p negatively and all obesity indicators positively. Using DAVID bioinformatics resources 6.8, top three pathways for obesity-related gene set were metabolic pathways, pathways in cancer, and PI3K-Akt signaling pathway. The top three obesity-related disease classes were metabolic, cardiovascular, and chemdependency. Our results support that childhood obesity could be developed through miRNAs-related epigenetic mechanism and, further, these obesity-related epigenetic changes could control the pathways related with the development of various diseases.

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Piwil1 Regulates Glioma Stem Cell Maintenance and Glioblastoma Progression

Cited by 47 publications

References 53 publications

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

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

Identification and functional analysis of a three-miRNA ceRNA network in hypertrophic scars

Childhood Obesity-Related Mechanisms: MicroRNome and Transcriptome Changes in a Nested Case-Control Study

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