DHH is an Independent Prognosticator of Oncologic Outcome of Clear Cell Renal Cell Carcinoma

Jäger, Wolfgang; Thomas, Christian; Fazli, Ladan; Hurtado-Coll, Antonio; Li, Estelle; Janßen, Claudia; Gust, Kilian M.; So, Alan; Hainz, Michael; Schmidtmann, Irene; Roos, Frederik C.; Thüroff, Joachim W.; Brenner, Walburgis; Black, Peter C.

doi:10.1016/j.juro.2014.07.013

Cited by 20 publications

(17 citation statements)

References 31 publications

(40 reference statements)

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“…5'-AUAGUGAAUUAAGCUUCGCGAGUUAUAG-3' such as the synthetic contribution of hypoxia inducible factor 1 (HIFlα) and CD74 to inhibiting KIRC cells' growth and invasion, 26 and the independently predictive role of DHH for KIRC prognosis. 27 In this investigation, MALAT1 was observed to differentially express within KIRC tissues and adjacent normal tissues, manifesting that this lncRNA potentially marked the onset and progression of KIRC ( Figure 1). Virtually, MALAT1 was ubiquitously expressed with a conservation degree of up to 90% among humans and mice, and the transcriptional products of MALAT1 were extremely stable due to that the triple helix structure in its 3′-end could prevent its degradation.…”

Section: Acvr2b Was Targeted By Mir-194-5p In Kirc Cellsmentioning

confidence: 58%

“…Plenty of documentations also related various genes with KIRC, such as the synthetic contribution of hypoxia inducible factor 1 (HIF‐lα) and CD74 to inhibiting KIRC cells’ growth and invasion, and the independently predictive role of DHH for KIRC prognosis . In this investigation, MALAT1 was observed to differentially express within KIRC tissues and adjacent normal tissues, manifesting that this lncRNA potentially marked the onset and progression of KIRC (Figure ).…”

Section: Discussionmentioning

confidence: 69%

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LncRNA MALAT1 modified progression of clear cell kidney carcinoma (KIRC) by regulation of miR‐194‐5p/ACVR2B signaling

Zhang

Chen

et al. 2018

Molecular Carcinogenesis

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This investigation was purposed to extrapolate whether and how lncRNA MALAT1, miR‐194‐5p, and ACVR2B altered development of clear cell kidney carcinoma (KIRC). We totally gathered 318 pairs of KIRC tissues and adjacent normal tissues, and also purchased human KIRC cell lines and normal human proximal tubular epithelial cell line. Besides, si‐MALAT1, pcDNA‐MALAT1, miR‐194‐5p mimic, miR‐194‐5p inhibitor, and negative control (NC) were, respectively, transfected into KIRC cells. The viability, proliferation, and apoptosis of the cells were determined with CCK‐8 assay, colony formation assay, and flow cytometry. Dual‐luciferase reporter gene assay was implemented to validate the targeted relationships between MALAT1 and miR‐194‐5p, as well as between miR‐194‐5p and ACVR2B. The results showed that highly expressed MALAT1, ACVR2B, and lowly expressed miR‐194‐5p were associated with larger tumor size (≥4 cm), advanced TNM stage and poor prognosis of KIRC patients, when, respectively, compared with lowly expressed MALAT1, ACVR2B, and highly expressed miR‐194‐5p (P < 0.05). Transfection of pcDNA‐MALAT1, miR‐194‐5p inhibitor, and pcDNA‐ACVR2B conferred the KIRC cells with promoted viability and proliferation, as well as reduced apoptosis (P < 0.05). Treatment of rats with pcDNA‐MALAT1, miR‐194‐5p inhibitor, or pcDNA‐ACVR2B also contributed to larger tumor size growing in them (P < 0.05). Moreover, MALAT1 could directly target miR‐194‐5p to suppress its expression, and ACVR2B was the targeted molecule of miR‐194‐5p (P < 0.05). Finally, ACVR2B could reverse the effects exerted by miR‐194‐5p on viability, proliferation, and apoptosis of KIRC cells (P < 0.05). In conclusion, LncRNA MALAT1/miR‐194‐5p/ACVR2B signaling was regarded as a candidate pathway for modulating KIRC progression.

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Section: Acvr2b Was Targeted By Mir-194-5p In Kirc Cellsmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 69%

LncRNA MALAT1 modified progression of clear cell kidney carcinoma (KIRC) by regulation of miR‐194‐5p/ACVR2B signaling

Zhang

Chen

et al. 2018

Molecular Carcinogenesis

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“…Over-expression of SHH, DHH and GLI1 was significantly correlated with advanced stages and tumour grades of the cohort. Activation of hedgehog pathway in advance cancer stages has been reported previously in breast [ 25 , 32 ], ovarian [ 18 ], renal [ 19 ] and prostate cancer [ 10 ]. Concomitantly, dysregulation of SHH, DHH and GLI-1 in the cohort has also been related with nodal involvement and metastasis.…”

Section: Discussionmentioning

confidence: 82%

Involvement of hedgehog pathway in early onset, aggressive molecular subtypes and metastatic potential of breast cancer

et al. 2018

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BackgroundDysregulation of hedgehog pathway is observed in numerous cancers. Relevance of hedgehog pathway genes in cancer cohort and inhibition of its downstream effector (GLI1) towards metastasis in cell lines are explored in the study.MethodOne hundred fifty fresh tumours of breast cancer patients were collected for the study. Based on differential expression, panel of 6 key regulators of the pathway (SHH, DHH, IHH, PTCH1, SMO and GLI1) in microarray datasets were identified. Expressional profiles of aforementioned genes were later correlated with clinico-pathological parameters in Pakistani breast cancer cohort at transcript and protein levels. In addition, GLI1 over expressing breast cancer cell lines (MDA-MB-231 and MCF-7) were treated with GANT61 to explore its probable effects on metastasis.ResultSHH, DHH, PTCH1 and GLI1 were significantly over-expressed in tumours as compared with respective normal mammary tissues. A significant correlation of SHH, DHH and GLI1 expression with advanced tumour size, stages, grades, nodal involvement and distant metastasis was observed (p < 0.05). Over-expression of SHH, DHH and GLI1 was significantly related with patients having early onset and pre-menopausal status. Of note, hedgehog pathway was frequently up regulated in luminal B and triple negative breast cancer affected women. In addition, positive correlations were observed among aforementioned members of pathway and Ki67 (r-value: 0.63–0.78) emphasizing their role towards disease progression. Exposure of GANT61 (inhibitor for GLI1) significantly restricted cell proliferation, reduced cell motility and invasion.ConclusionRole of activated hedgehog pathway in breast cancer metastasis provides a novel target for cancer therapy against aggressive cancer subtypes.Electronic supplementary materialThe online version of this article (10.1186/s12964-017-0213-y) contains supplementary material, which is available to authorized users.

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“…Both IHH and SHH are highly expressed in human gastric cancer . DHH has prognostic value in clear cell renal cell carcinoma whereas IHH plays a role in squamous cell carcinoma progression and metastasis . In human osteosarcoma cell lines, IHH has been found to be upregulated, and inhibition of signaling leads to decreased xenograft tumor size .…”

Section: Discussionmentioning

confidence: 99%

Hedgehog signaling is activated in canine transitional cell carcinoma and contributes to cell proliferation and survival

Gustafson

Kitchell

Biller

2015

Vet Comparative Oncology

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Transitional cell carcinoma (TCC) is the most commonly diagnosed tumor of the canine urinary system. Hedgehog (HH) signaling represents one possible novel therapeutic target, based on its recently identified central role in human urothelial carcinoma. The purpose of this study was to determine if HH mediators are expressed in canine TCC and the effect of inhibition of this pathway on cell growth and survival. HH pathway mediators were found to be expressed in five canine TCC cell lines. Indian HH was expressed in tumor cells in five canine bladder tumor tissues, but not in normal canine bladder tissue. Inhibition of HH signaling with cyclopamine and GANT61 led to significantly decreased cell proliferation but had a smaller effect on apoptosis. These results support future investigation of inhibitors of HH signaling in the treatment of canine TCC.

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DHH is an Independent Prognosticator of Oncologic Outcome of Clear Cell Renal Cell Carcinoma

Cited by 20 publications

References 31 publications

LncRNA MALAT1 modified progression of clear cell kidney carcinoma (KIRC) by regulation of miR‐194‐5p/ACVR2B signaling

LncRNA MALAT1 modified progression of clear cell kidney carcinoma (KIRC) by regulation of miR‐194‐5p/ACVR2B signaling

Involvement of hedgehog pathway in early onset, aggressive molecular subtypes and metastatic potential of breast cancer

Hedgehog signaling is activated in canine transitional cell carcinoma and contributes to cell proliferation and survival

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