Decreased expression levels of PIWIL1, PIWIL2, and PIWIL4 are associated with worse survival in renal cell carcinoma patients

Iliev, Robert; Staník, Michal; Fedorko, Michal; Poprach, Alexandr; Vychytilova-Faltejskova, Petra; Slabá, Kateřina; Svoboda, Marek; Fabián, Pavel; Pacík, Dalibor; Doležel, Jan; Slabý, Ondřej

doi:10.2147/ott.s91295

Cited by 22 publications

(13 citation statements)

References 22 publications

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“…Recently, the PIWI protein family has been the subject of intense studies. The expression of PIWIL proteins varies in different tumors and, as reported recently, PIWIL1, PIWIL2, and PIWIL4 are expressed at low levels in human renal cell carcinoma and are related to shortened survival 33 . PIWIL2 has weak cytoplasmic but no nuclear expression and is associated with the progression of bladder cancer, suggesting it acts as a tumor suppressor 34 .…”

Section: Discussionmentioning

confidence: 56%

PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop regulates the biological behavior of glioma cells

et al. 2018

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Rationale: PIWI-interacting RNAs (piRNAs), a class of newly discovered small RNA molecules that function by binding to the Argonaute protein family (i.e., the PIWIL protein subfamily), and long noncoding RNAs (lncRNA) are implicated in several cancers. However, the detailed roles of ncRNAs in glioma remain unclear.Methods: The expression of PIWIL3, piR-30188, OIP5-AS1, miR-367, CEBPA and TRAF4 were measured in glioma tissues and cells. The role of PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop was evaluated in cell and animal models. The association of the above molecules was analyzed.Results: Over-expression of PIWIL3, piR-30188 and miR-367-3p or knockdown of OIP5-AS1 resulted in inhibition of glioma cells progression. Binding sites between piR-30188 and OIP5-AS1 as well as between OIP5-AS1 and miR-367-3p were confirmed by RNA immunoprecipitation and luciferase assays. OIP5-AS1 knockdown or miR-367-3p over-expression contributed to a decrease in CEBPA (CCAAT/enhancer binding protein alpha) protein. Furthermore, CEBPA was detected as a target of miR-367-3p and played an oncogenic role in glioma. Treatment with CEBPA and miR-367-3p resulted in the modulation of downstream TRAF4 (TNF receptor-associated factor 4). PIWIL3 was also a target of CEBPA, forming a positive feedback loop in the growth regulation of glioma cells. Significantly, knockdown of OIP5-AS1 combined with over-expression of PIWIL3 and miR-367-3p resulted in tumor regression and extended survival in vivo.Conclusion: These results identified a novel molecular pathway in glioma cells that may provide a potential innovative approach for tumor therapy.

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Section: Discussionmentioning

confidence: 56%

PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop regulates the biological behavior of glioma cells

et al. 2018

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“…Of the four human homologues of PIWI genes, two genes (PIWIL3 and PIWIL4) showed associations with OS, and PIWIL3 alone showed association with RFS (Table 5, Figure 5A and 5B). Reports on the clinical significance of PIWIL3 and PIWIL4 remain scarce [34–36], and in particular, this is the first study to identify the contribution of PIWIL3 and PIWIL4 genes to breast cancer prognosis. Further replication studies are warranted to better define their prognostic roles.…”

Section: Discussionmentioning

confidence: 99%

Piwi-interacting RNAs and PIWI genes as novel prognostic markers for breast cancer

et al. 2016

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Piwi-interacting RNAs (piRNAs), whose role in germline maintenance has been established, are now also being classified as post-transcriptional regulators of gene expression in somatic cells. PIWI proteins, central to piRNA biogenesis, have been identified as genetic and epigenetic regulators of gene expression. piRNAs/PIWIs have emerged as potential biomarkers for cancer but their relevance to breast cancer has not been comprehensively studied. piRNAs and mRNAs were profiled from normal and breast tumor tissues using next generation sequencing and Agilent platforms, respectively. Gene targets for differentially expressed piRNAs were identified from mRNA expression dataset. piRNAs and PIWI genes were independently assessed for their prognostic significance (outcomes: Overall Survival, OS and Recurrence Free Survival, RFS). We discovered eight piRNAs as novel independent prognostic markers and their association with OS was confirmed in an external dataset (The Cancer Genome Atlas). Further, PIWIL3 and PIWIL4 genes showed prognostic relevance. 306 gene targets exhibited reciprocal relationship with piRNA expression. Cancer cell pathways such as apoptosis and cell signaling were the key Gene Ontology terms associated with the regulated gene targets. Overall, we have captured the entire cascade of events in a dysregulated piRNA pathway and have identified novel markers for breast cancer prognostication.

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“…Previous studies revealed that significant decreases in Hiwi expression were observed in renal cell carcinoma, and Hiwi expression was found to be inversely associated with overall survival ( 25 , 26 ). Functional analysis of Hiwi protein has also generated conflicting results.…”

Section: Discussionmentioning

confidence: 98%

Hiwi overexpression does not affect proliferation, migration or apoptosis of liver cancer cells inï¿½vitro or inï¿½vivo

Shi

Liu

et al. 2018

Oncol Lett

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Piwi like RNA-mediated gene silencing 1 (Hiwi) is a human homolog of the Piwi gene family that has been reported to be upregulated in hepatocellular carcinoma (HCC). The present study aimed to investigate the role of Hiwi in the initiation and development of HCC in vitro and in vivo. Adenovirus-mediated Hiwi overexpression was established in primary murine hepatocytes and SMMC7721 HCC cells. Cell viability and proliferation were assessed using MTT and EdU assays, respectively. Cell migration was measured using a scratch migration assay. The cell cycle was assessed using flow cytometry, and the expression of genes associated with the epithelial mesenchymal transition (EMT) was assessed using reverse transcription-quantitative polymerase chain reaction. SMMC7721 cells that stably express Hiwi were also generated and injected subcutaneously into the nude mice, and tumor growth was examined. Recombinant adenovirus encoding green fluorescent protein or Hiwi was delivered by injection into the tail vein, and its effect on murine hepatocyte gene expression was studied. The present study revealed that the overexpression of Hiwi did not affect the proliferation or migration of liver cancer cells and failed to suppress perifosine- or doxorubicin-induced apoptosis in vitro. The tumors of mice that were injected with Hiwi-expressing SMMC7721 cells were not significantly larger compared with mice that were injected with control SMMC7721 cells. Hiwi overexpression did not noticeably alter the expression of genes involved in EMT, either in vitro or in vivo. The results of the present study indicate that although expression of Hiwi is associated with HCC development and progression in the clinic, it does not act as an oncogene in liver cancer cells.

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Decreased expression levels of PIWIL1, PIWIL2, and PIWIL4 are associated with worse survival in renal cell carcinoma patients

Cited by 22 publications

References 22 publications

PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop regulates the biological behavior of glioma cells

PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop regulates the biological behavior of glioma cells

Piwi-interacting RNAs and PIWI genes as novel prognostic markers for breast cancer

Hiwi overexpression does not affect proliferation, migration or apoptosis of liver cancer cells inï¿½vitro or inï¿½vivo

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