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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
HOXD1 functions as a novel tumor suppressor in kidney renal clear cell carcinoma
Yuanbo Cui1,2, Chunyan Zhang3, Ya Li2
1Department of Translational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Abstract:
Kidney renal clear cell carcinoma (KIRC) is a common malignant tumor in human genitourinary system. Previous studies have shown that the homeobox-D (HOXD) cluster genes, which belong to the homeobox (HOX) family, are involved in the progression of multiple types of cancer. However, the expression profile and prognostic values of the HOXD genes in KIRC remain largely unknown. Herein, we comprehensively analyzed the transcriptional levels and prognosis of HOXD genes in KIRC using four online The Cancer Genome Atlas analysis databases (GEPIA, UALCAN, starBase v3.0, and LinkedOmics). We found that several members of the HOXD gene family were abnormally expressed in KIRC and correlated with patient prognosis. The messenger RNA levels of HOXD1, HOXD8, and HOXD10 were significantly downregulated in KIRC tissues as compared with the normal tissues. Low expression of HOXD1 or HOXD8 predicted poor overall survival (OS) of KIRC patients, and downregulated HOXD1, HOXD3, or HOXD4 indicated unfavorable patient disease-free survival (DFS) in KIRC. Through integrated analysis, we found that HOXD1 was lowly expressed in KIRC and correlated with patient OS, DFS and advanced tumor stages. Moreover, gene set enrichment analysis showed that HOXD1 may be mainly implicated in cell cycle regulation, tumor growth factor-β (TGF-β) and Wnt signaling pathways in KIRC. Furthermore, both loss-of-function and gain-of-function experiments demonstrated that HOXD1 inhibited cell proliferation, cell cycle and the TGF-β signaling in KIRC. Taken together, our findings suggest that HOXD1 is a novel potential tumor suppressor in KIRC.
Insights
Homeobox-D (HOXD) genes, including HOXD1, are dysregulated in kidney renal clear cell carcinoma (KIRC). Low HOXD1 expression indicates poor prognosis and suggests HOXD1 acts as a tumor suppressor in KIRC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Kidney renal clear cell carcinoma (KIRC) is a prevalent genitourinary malignancy.
- The homeobox-D (HOXD) gene cluster's role in KIRC progression is largely uncharacterized.
- Understanding HOXD gene expression is crucial for identifying KIRC biomarkers.
Purpose of the Study:
- To investigate the expression patterns and prognostic significance of HOXD genes in KIRC.
- To elucidate the functional role of HOXD1 in KIRC development and progression.
Main Methods:
- Comprehensive analysis of HOXD gene expression and survival data using TCGA databases (GEPIA, UALCAN, starBase v3.0, LinkedOmics).
- Gene Set Enrichment Analysis (GSEA) to identify associated signaling pathways.
- In vitro loss-of-function and gain-of-function experiments to assess HOXD1's functional impact.
Main Results:
- HOXD1, HOXD8, and HOXD10 mRNA levels were significantly downregulated in KIRC tissues.
- Low expression of HOXD1 or HOXD8 correlated with poor overall survival (OS).
- Downregulated HOXD1, HOXD3, or HOXD4 predicted unfavorable disease-free survival (DFS).
- HOXD1 downregulation was associated with advanced tumor stages and correlated with OS and DFS.
- HOXD1 was implicated in cell cycle regulation, TGF-β, and Wnt signaling pathways.
- HOXD1 inhibited KIRC cell proliferation, cell cycle, and TGF-β signaling.
Conclusions:
- HOXD1 is frequently downregulated in KIRC and serves as a potential prognostic biomarker.
- HOXD1 exhibits tumor-suppressive functions by inhibiting cell proliferation and key signaling pathways.
- Targeting HOXD1 may offer a novel therapeutic strategy for KIRC.
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