| Autor: |
Kamada, Shuhei, Ikeda, Kazuhiro, Suzuki, Takashi, Sato, Wataru, Kitayama, Sachi, Kawakami, Satoru, Ichikawa, Tomohiko, Horie, Kuniko, Inoue, Satoshi |
| Předmět: |
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| Zdroj: |
Frontiers in Oncology; 11/3/2021, Vol. 11, p1-12, 12p |
| Abstrakt: |
Background: Acquired therapeutic resistance and metastasis/recurrence remain significant challenge in advance renal cell carcinoma (RCC), thus the establishment of patient-derived cancer models may provide a clue to assess the problem. We recently characterized that neuritogenesis-related protein neuritin 1 (NRN1) functions as an oncogene in testicular germ cell tumor. This study aims to elucidate the role of NRN1 in RCC. Methods: NRN1 expression in clinical RCC specimens was analyzed based on immunohistochemistry. NRN1 -associated genes in RCC were screened by the RNA-sequencing dataset from The Cancer Genome Atlas (TCGA). RCC patient-derived cancer cell (RCC-PDC) spheroid cultures were established and their viabilities were evaluated under the condition of gene silencing/overexpression. The therapeutic effect of NRN1-specific siRNA was evaluated in RCC-PDC xenograft models. Results: NRN1 immunoreactivity was positively associated with shorter overall survival in RCC patients. In TCGA RCC RNA-sequencing dataset, C-X-C chemokine receptor type 4 (CXCR4), a prognostic and stemness-related factor in RCC, is a gene whose expression is substantially correlated with NRN1 expression. Gain- and loss-of-function studies in RCC-PDC spheroid cultures revealed that NRN1 significantly promotes cell viability along with the upregulation of CXCR4. The NRN1-specific siRNA injection significantly suppressed the proliferation of RCC-PDC-derived xenograft tumors, in which CXCR4 expression is significantly repressed. Conclusion: NRN1 can be a potential diagnostic and therapeutic target in RCC as analyzed by preclinical patient-derived cancer models and clinicopathological studies. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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