Expression of the Sonic Hedgehog pathway components in clear cell renal cell carcinoma

Kotulak-Chrząszcz, Anna; Kłącz, Jakub; Matuszewski, Marcin; Kmieć, Zbigniew; Wierzbicki, Piotr M.

doi:10.3892/ol.2019.10919

Cited by 15 publications

(26 citation statements)

References 39 publications

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“…One paper detected the immunohistochemical expression of PTCH1 in 140 ccRCC specimens and found that PTCH1 is more highly expressed in G3/G4 than in G1/G2 tumors (1.5-fold, p = 0.02) 50 , which was consistent with our findings of circPTCH1. Another study evaluated the expression of PTCH1 in 37 ccRCC tumor and control tissues, however, no statistically significant differences were observed 51 . Though circRNAs are typically described as having a similar function as their linear counterparts, antagonistic and independent functions of linear and circular RNA have also been reported previously.…”

Section: Discussionmentioning

confidence: 99%

circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis

Liu¹,

Hu²,

Wang³

et al. 2020

Theranostics

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Background: Circular RNAs (circRNAs) are a new class of non-coding RNAs (ncRNAs) that are derived from exons or introns by special selective shearing. circRNAs have been shown to play critical roles in various human cancers. However, their roles in renal cell carcinoma (RCC) and the underlying mechanisms remain largely unknown. Methods: A novel circRNA-circPTCH1, was identified from a microarray analysis of five paired RCC tissues. Then, we validated its expression and characterization through qRT-PCR, gel electrophoresis, RNase R digestion assays and Sanger sequencing. Functional experiments were performed to determine the effect of circPTCH1 on RCC progression both in vitro and in vivo . The interactions between circPTCH1 and miR-485-5p were clarified by RNA pull-down, luciferase reporter and RNA immunoprecipitation (RIP) assays. Results: We observed that circPTCH1 was up-regulated in RCC cell lines and tumor samples, and higher levels of circPTCH1 were significantly correlated with worse patient survival, advanced Fuhrman grade and greater risk of metastases. Elevated circPTCH1 expression led to increased migration and invasion of RCC cells both in vitro and in vivo whereas silencing circPTCH1 decreased migration and invasion and impeded the epithelial-mesenchymal transition (EMT) of RCC cells. Mechanistically, we elucidated that circPTCH1 could directly bind miR-485-5p and subsequently suppress expression of the target gene MMP14. Conclusion: circPTCH1 promotes RCC metastasis via the miR-485-5p/MMP14 axis and activation of the EMT process. Targeting circPTCH1 may represent a promising therapeutic strategy for metastatic RCC.

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Section: Discussionmentioning

confidence: 99%

circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis

Liu¹,

Hu²,

Wang³

et al. 2020

Theranostics

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“…In a previous study by the authors ( 143 ), the expression of SHH pathway components in 37 ccRCC tissue samples, a significant correlation was identified among the expression of almost all SHH signaling genes at the mRNA level. Although the mRNA level of SHH , SMO and GLI1 was increased in ccRCC samples, compared to the morphologically unaltered kidney tissues, no association was observed between the expression rates of genes and the pathological features of patients.…”

Section: Sonic Hedgehog Signaling In Cancers Of the Urinary Tractmentioning

confidence: 81%

“…Since several studies have reported a SHH gene upregulation in RCC ( 140 , 142 , 143 ), the present review focused on the occurrence of the upstream protein and miRNA regulators of SHH expression in RCC. Shang et al ( 144 ) analyzed the mRNA expression rates of the ZIC2 gene in 533 ccRCC and 72 normal kidney samples (TCGA database), and found that the overexpression of ZIC2 mRNA was associated with age, TNM, histological grade and a shorter overall survival; thus, this gene can therefore be used as an independent prognostic factor in ccRCC.…”

Section: Sonic Hedgehog Signaling In Cancers Of the Urinary Tractmentioning

confidence: 99%

“…Although the mRNA level of SHH , SMO and GLI1 was increased in ccRCC samples, compared to the morphologically unaltered kidney tissues, no association was observed between the expression rates of genes and the pathological features of patients. However, at the protein level, western blot analysis of SHH revealed a significant increase of full-length SHH and a decrease of the C-SHH domain in ccRCC tissues ( 143 ). This novel observation may suggest an involvement of the SHH ligand in ccRCC development, and indicate changes in the post-translational modification of this protein during tumor progression.…”

Section: Sonic Hedgehog Signaling In Cancers Of the Urinary Tractmentioning

confidence: 99%

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Sonic Hedgehog signaling pathway in gynecological and genitourinary cancer (Review)

2021

Self Cite

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Cancers of the urinary tract, as well as those of the female and male reproductive systems, account for a large percentage of malignancies worldwide. Mortality is frequently affected by late diagnosis or therapeutic difficulties. The Sonic Hedgehog (SHH) pathway is an evolutionary conserved molecular cascade, which is mainly associated with the development of the central nervous system in fetal life. The present review aimed to provide an in-depth summary of the SHH signaling pathway, including the characterization of its major components, the mechanism of its upstream regulation and non-canonical activation, as well as its interactions with other cellular pathways. In addition, the three possible mechanisms of the cellular SHH cascade in cancer tissue are discussed. The aim of the present review was to summarize significant findings with regards to the expression of the SHH pathway components in kidney, bladder, ovarian, cervical and prostate cancer. Reports associated with common deficits and de-regulations of the SHH pathway were summarized, despite the differences in molecular and histological patterns among these malignancies. However, currently, neither are SHH pathway elements included in panels of prognostic/therapeutic molecular patterns in any of the discussed cancers, nor have the drugs targeting SMO or GLIs been approved for therapy. The findings of the present review may support future studies on the treatment of and/or molecular targets for gynecological and genitourinary cancers.

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“…In early embryonic development, GLI members play a major role in the central nervous system; however, it is also involved in carcinogenesis and metastatic cascade niche ( Niewiadomski et al, 2019 ). Since amplified GLI was first observed in glioblastoma, it has now been commonly detected in the breast ( Song et al, 2016 ), lung ( Panneerselvam et al, 2019 ), pancreatic ( Kowolik et al, 2019 ), colorectal ( Park et al, 2019 ), leukemia ( Jetten, 2019 ), and renal cell carcinoma ( Kotulak-Chrzaszcz et al, 2019 ). It was also stated that high-expression GLI prevails tumor suppression mediated by p53 ( Abe et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

Systemic Multi-Omics Analysis Reveals Amplified P4HA1 Gene Associated With Prognostic and Hypoxic Regulation in Breast Cancer

Muthu

Premkumar

2021

Front. Genet.

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Breast cancer (BC) is a common malignant tumor in females around the world. While multimodality therapies exist, the mortality rate remains high. The hypoxic condition was one of the potent determinants in BC progression. The molecular mechanisms underpinning hypoxia and their association with BC can contribute to a better understanding of tailored therapies. In this study, two hypoxic induced BC transcriptomic cohorts (GSE27813 and GSE47533) were assessed from the GEO database. The P4HA1 gene was identified as a putative candidate and significantly regulated in hypoxic BC cells compared to normal BC cells at different time intervals (6 h, 9 h, 16 h, 32 h, and 48 h). In patients with Luminal (p < 1E-12), triple-negative subclasses (p = 1.35059E-10), Stage 1 (p = 8.8817E-16), lymph node N1 (p = 1.62436E-12), and in the 40–80 age group (p = 1.62447E-12), the expression of P4HA1 was closely associated with the clinical subtypes of BC. Furthermore, at the 10q22.1 chromosomal band, the P4HA1 gene displayed a high copy number elevation and was associated with a poor clinical regimen with overall survival, relapse-free survival, and distant metastases-free survival in BC patients. In addition, using BioGRID, the protein–protein interaction (PPI) network was built and the cellular metabolic processes, and hedgehog pathways are functionally enriched with GO and KEGG terms. This tentative result provides insight into the molecular function of the P4HA1 gene, which is likely to promote hypoxic-mediated carcinogenesis, which may favor early detection of BC and therapeutic stratification.

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Expression of the Sonic Hedgehog pathway components in clear cell renal cell carcinoma

Cited by 15 publications

References 39 publications

circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis

circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis

Sonic Hedgehog signaling pathway in gynecological and genitourinary cancer (Review)

Systemic Multi-Omics Analysis Reveals Amplified P4HA1 Gene Associated With Prognostic and Hypoxic Regulation in Breast Cancer

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