Piwi-like 1 and 4 gene transcript levels are associated with clinicopathological parameters in renal cell carcinomas

Al‐Janabi, Omar; Wach, Sven; Nolte, Elke; Weigelt, Katrin; Rau, Tilman T.; Stöhr, Christine; Schick, Stefan; Greither, Thomas; Hartmann, Arndt; Wullich, Bernd; Täubert, Helge

doi:10.1016/j.bbadis.2014.01.014

Cited by 30 publications

(16 citation statements)

References 25 publications

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“…oncomine.org) contains entries that suggest PIWIL 4 is expressed in brain cancers including glioma. 22 Moreover, using miRNA target prediction software Targetscan and miRanda, PIWIL4 was predicted to be a presumed target of miR-384. However, the expression and function of PIWIL4 in glioma still remain unclear.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: CRNDE Promotes Malignant Progression of Glioma by Attenuating miR-384/PIWIL4/STAT3 Axis

et al. 2016

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Colorectal neoplasia differentially expressed (CRNDE) is the most upregulated long noncoding RNA (lncRNA) in glioma. Herein, the function and potential molecular mechanisms of CRNDE and miR-384 were illustrated in glioma cells. CRNDE overexpression facilitated cell proliferation, migration, and invasion, while inhibited glioma cells apoptosis. Quantitative real-time polymerase chain reaction (PCR) demonstrated that miR-384 was downregulated in human glioma tissues and glioma cell lines. Moreover, restoration of miR-384 exerted tumor-suppressive functions. In addition, the expression of miR-384 was negatively correlated with CRNDE expression. A binding region between CRNDE and miR-384 was confirmed using luciferase assays. Moreover, CRNDE promoted cell malignant behavior by decreasing miR-384 expression. At the molecular level, treatment by CRNDE knockdown or miR-384 overexpression resulted in a decrease of piwi-like RNA-mediated gene silencing 4 (PIWIL4) protein. Besides, PIWIL4 was identified as a target of miR-384 and plays an oncogenic role in glioma. Similarly, downstream proteins of PIWIL4 such as STAT3, cyclin D1, VEGFA, SLUG, MMP-9, caspase 3, Bcl-2, and bcl-xL were modulated when treated with miR-384 and PIWIL4. Remarkably, CRNDE knockdown combined with miR-384 overexpression led to tumor regression in vivo. Overall, these results depicted a novel pathway mediated by CRNDE in glioma, which may be a potential application for glioma therapy.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: CRNDE Promotes Malignant Progression of Glioma by Attenuating miR-384/PIWIL4/STAT3 Axis

et al. 2016

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“…In agreement with our results, Al-Janabi et al described the trend of PIWIL1 expression to be decreased in RCC tumors ( P =0.089). 14 In addition, they observed a significantly higher level of PIWIL4 in tumors ( P <0.001), which was not shown in tumor tissues in our cohort of patients with RCC. Analogically, the expression of PIWIL genes is downregulated in seminoma and non-seminoma testicular tumors, probably due to the existence of promoter CpG island hypermethylation-associated silencing.…”

Section: Discussioncontrasting

confidence: 60%

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

Iliev

Staník

Fedorko

et al. 2016

OTT

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Piwi-interacting RNAs (piRNAs) are a newly discovered class of small non-coding RNAs involved in silencing of transposable elements and in sequence-specific chromatin modifications. PIWI proteins (PIWIL), which belong to the family of Argonaute genes/proteins, bind to piRNAs and function mainly in germ line cells, but more recently were described to be functional also in stem cells and cancer cells. To date, there have been four PIWI proteins discovered in humans: PIWIL1, PIWIL2, PIWIL3, and PIWIL4. Recent studies suggested that deregulated expression of PIWI proteins and selected piRNAs is common to many types of cancers. We found significantly lower expression of PIWIL1 (P<0.0001) and piR-823 (P=0.0001) in tumor tissue in comparison to paired renal parenchyma. Further, we observed a progressive decrease in PIWIL1 (P=0.0228), PIWIL2 (P=0.0015), and PIWIL4 (P=0.0028) expression levels together with increasing clinical stage. PIWIL2 (P=0.0073) and PIWIL4 (P=0.0001) expression also progressively decreased with increasing Fuhrman grade. Most importantly, low-expression levels of PIWIL1 (P=0.009), PIWIL2 (P<0.0001), and PIWIL4 (P=0.0065) were significantly associated with worse overall survival in renal cell carcinoma (RCC) patients. Our results suggest the involvement of PIWIL genes and piR-823 in RCC pathogenesis, and indicate PIWIL1, PIWIL2, and PIWIL4 as potential prognostic biomarkers in patients with RCC.

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“…However, a correlation between the expression of both Piwi-like proteins could be expected as they show on the protein level 34% sequence homology 35 . We could show that transcript levels of Piwi-like 1 and -2 were significantly correlated in renal cell carcinoma 36 , but a reciprocal regulation of Piwi-like 1 and Piwi-like 2 at the RNA level has been suggested in colorectal cancer 37 . We detected a negative correlation between Piwi-like 1/-2 protein expression and Ki67 protein expression.…”

Section: Discussionmentioning

confidence: 79%

Piwi-like 1 and -2 protein expression levels are prognostic factors for muscle invasive urothelial bladder cancer patients

Eckstein

Jung

Weigelt

et al. 2018

Sci Rep

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Piwi-like proteins are essential for stem-cell maintenance and self-renewal in multicellular organisms. We analyzed the expression of Piwi-like 1 and Piwi-like 2 by immunohistochemistry (IHC) in 95 muscle invasive bladder cancer (MIBC) samples using tissue microarray. Application of an immunoreactive score (IRS) revealed 37 and 45 patients who were Piwi-like 1 and -2 positive (IRS > 2). IHC results were correlated with clinico-pathological and survival data. The expression of both proteins was positively correlated with each other, lymph node metastasis and expression of CK20 and GATA 3. A negative correlation for both proteins was detected for disease-specific survival (DSS), recurrence, Ki67/MIB1 proliferation index, and CK5 expression. Detection of Piwi-like 1 protein positivity was associated with poor DSS (P = 0.019; log rank test, Kaplan-Meier analysis), and in multivariate Cox’s analysis (adjusted to tumor stage and tumor grade), it was an independent prognostic factor for DSS (RR = 2.16; P = 0.011). Piwi-like 2 positivity was associated with DSS (P = 0.008) and recurrence-free survival (RFS; P = 0.040), and in multivariate Cox’s analysis, Piwi-like 2 positivity was an independent prognostic factor for DSS (RR = 2.46; P = 0.004) and RFS (RR = 3.0; P = 0.003). Most interestingly, in the basal type patient subgroup (CK5+/GATA3−), Piwi-like 2 positivity was associated with poorer DSS, OS and RFS (P < 0.001, P = 0.004 and P = 0.05; log rank test). In multivariate analysis, Piwi-like 2 positivity was an independent prognostic factor for DSS (RR = 12.70; P = 0.001), OS (RR = 6.62; = 0.008) and RFS (RR=13.0; P = 0.040). In summary, Piwi-like 1 and -2 positivity are associated with clinico-pathological factors and survival. Both Piwi-like proteins are suggested as biomarkers for MIBC patients.

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Piwi-like 1 and 4 gene transcript levels are associated with clinicopathological parameters in renal cell carcinomas

Cited by 30 publications

References 25 publications

RETRACTED: CRNDE Promotes Malignant Progression of Glioma by Attenuating miR-384/PIWIL4/STAT3 Axis

RETRACTED: CRNDE Promotes Malignant Progression of Glioma by Attenuating miR-384/PIWIL4/STAT3 Axis

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

Piwi-like 1 and -2 protein expression levels are prognostic factors for muscle invasive urothelial bladder cancer patients

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