2022
DOI: 10.3892/ijmm.2022.5114
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Expression levels of sonic hedgehog pathway genes and their targets are upregulated in early clear cell renal cell carcinoma

Abstract: Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of kidney cancer, with high mortality rates worldwide. The sonic hedgehog (SHH) molecular cascade is altered in various malignancies in tumorigenesis, and several SHH pathway inhibitors have been considered as potential anticancer drugs. The aim of the present study was to determine the expression profile of SHH signaling components and their target genes in ccRCC. Additionally, the present study examined the effects of SHH pathw… Show more

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Cited by 15 publications
(8 citation statements)
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“…In CDH, the histological abnormalities observed in the lung are accompanied by lower SHH expression as compared to normal lung development [72]; therefore, we investigated HH pathway expression in CDH (Figures 6 and S4). Consistent with previous reports, we demonstrated a downregulation of the expression of SHH in CDH [57]. Additionally, we show that PTCH1 and HHIP are also decreased in CDH.…”
Section: Discussionsupporting
confidence: 93%
See 1 more Smart Citation
“…In CDH, the histological abnormalities observed in the lung are accompanied by lower SHH expression as compared to normal lung development [72]; therefore, we investigated HH pathway expression in CDH (Figures 6 and S4). Consistent with previous reports, we demonstrated a downregulation of the expression of SHH in CDH [57]. Additionally, we show that PTCH1 and HHIP are also decreased in CDH.…”
Section: Discussionsupporting
confidence: 93%
“…The third class contains inhibitors that act on different phases of production, activation, and binding of the SHH ligand, such as RU-SKI 43 (SHH palmitoylation) or 5E1 (binding) [35,56]. Therefore, we used the SHH antibody 5E1, a strong candidate to safely interfere with HH signaling in clinical trials [57] with limited off-target effects, to abrogate HH activation in our human culture model [17,35]. We showed a strong decrease in the number of branches and an evident increase in cyst dilatation upon HH pathway inhibition, suggesting an involvement in lung branching (Figure 2).…”
Section: Discussionmentioning
confidence: 99%
“…Similar to these ndings, our data show that treatment of HT-29 colorectal cancer cell line with cyclopamine at a concentration of 2.5 µmol/L for 48 hours resulted in increased cells apoptosis, increased expression of the Bax and Caspase 3 genes, as well as decreased colony formation. According to another study, inhibiting the Shh pathway using Cyclopamine, can suppress the growth of kidney cancer cells in the G2/M phase of the cell cycle and decrease the expression of the GLI1, BCL2, VEGFA, and Cyclin D1 genes [40]. In contrast, BCL2 and Cyclin D1 gene expression were not decreased in our study by cyclopamine treatment.…”
Section: Discussioncontrasting
confidence: 49%
“…Shh was abnormally elevated in various cancers and could serve as a potential biomarker to predict poor prognosis [25]. Downregulation of Shh could effectively inhibit progression of cancer [26][27][28]. It was verified that abnormal activation of Hedgehog pathway could lead to a variety of malignancies, including cervical cancer [29].…”
Section: Biomed Research Internationalmentioning
confidence: 98%