KDF1, a Novel Tumor Suppressor in Clear Cell Renal Cell Carcinoma

KDF1 has been identified as a key regulator of epidermal proliferation and differentiation, but it is unknown whether KDF1 is involved in the pathogenesis of malignancy. No study has reported the expression and function of KDF1 in renal cancer. To explore the pathologic significance of KDF1 in clear cell renal cell carcinoma (ccRCC), the expression level of KDF1 protein in the tumor tissue of ccRCC patients was examined by immunohistochemistry and Western blot while the expression level of KDF1 mRNA was analyzed by using the data from TCGA database. In vitro cell experiments and allogeneic tumor transplantation tests were performed to determine the effects of altered KDF1 expression on the phenotype of ccRCC cells. Both the KDF1 mRNA and protein were found to be decreasingly expressed in the tumor tissue of ccRCC patients when compared with the adjacent non-tumor control tissue. The expression level of KDF1 in the tumor tissue was found to correlate negatively with the tumor grade. Patients with higher KDF1 in the tumor tissue were found to have longer overall survival and disease-specific survival time. KDF1 was shown to be an independent factor influencing the disease-specific survival of the ccRCC patients. Overexpression of KDF1 was found to inhibit the proliferation, migration and invasion of ccRCC cells, which could be reversed by decreasing the expression of KDF1 again. ccRCC cells with KDF1 overexpression were found to produce smaller transgrafted tumors. These results support the idea that KDF1 is involved in ccRCC and may function as a tumor suppressor.

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Nomograms for predicting long-term overall survival and disease-specific survival of patients with clear cell renal cell carcinoma

OncoTargets and Therapy ◽

10.2147/ott.s171881 ◽

2018 ◽

Vol Volume 11 ◽

pp. 5535-5544 ◽

Cited By ~ 18

Author(s):

Guanghao Zhang ◽

Yun Wu ◽

Jiashu Zhang ◽

Zhiqing Fang ◽

Zhaoxu Liu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Disease Specific Survival ◽

Cell Renal Cell Carcinoma ◽

Disease Specific

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Karyotyping of resected clear cell renal cell carcinoma: Loss of chromosome 4 predicts a worse disease-specific survival

European Urology Supplements ◽

10.1016/s1569-9056(18)30900-x ◽

2018 ◽

Vol 17 (2) ◽

pp. e71

Author(s):

M.W. Van Hattem ◽

L. Renkens ◽

M. Debiec-Rychter ◽

J. Berkers ◽

B. Van Cleynenbreugel ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Disease Specific Survival ◽

Chromosome 4 ◽

Cell Renal Cell Carcinoma ◽

Disease Specific

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Mammalian SIRT4 is a tumor suppressor of clear cell renal cell carcinoma by inhibiting cancer proliferation, migration and invasion

Cancer Biomarkers ◽

10.3233/cbm-191253 ◽

2020 ◽

Vol 29 (4) ◽

pp. 453-462 ◽

Cited By ~ 2

Author(s):

Changming Wang ◽

Chiyuan Piao ◽

Junlong Liu ◽

Zhe Zhang ◽

Yuyan Zhu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Tumor Suppressor ◽

Cell Carcinoma ◽

Survival Data ◽

Renal Cell ◽

Clear Cell ◽

Expression Level ◽

Migration And Invasion ◽

Advanced Tumor Stage ◽

Cell Renal Cell Carcinoma

OBJECTIVE: Sirtuins family are defined as class III histone deacetylases (HDACs). Recently, mammalian silent information regulator two 4 (SIRT4) has been reported to be a tumor suppressor gene in multiple cancers. The objective of the present study was to explore the potential role of SIRT4 in clear cell renal cell carcinoma (ccRCC). METHODS: We estimated SIRT4 expression levels in ccRCC and its adjacent non-neoplastic tissue by Western blotting (WB), quantitative real-time polymerase chain reaction (qRT-PCR) and bioinformatics data, the clinical and survival data were also collected and analyzed. In vitro study, ccRCC cell lines were transfected with SIRT4-siRNA or lentivirus to downregulate or overexpress the expression level of SIRT4. Then, the proliferation capacity of tumor cell was assessed by 5-Ethynyl-2’-deoxyuridine (EDU) assay, cell migration and invasion capacity were assessed by Transwell assays. RESULTS: Our results indicated that the expression level of SIRT4 in ccRCC was significantly lower than the corresponding normal tissues (P< 0.001). Meanwhile, bioinformatics data and the result of WB showed that low SIRT4 expression level was obviously involved with poor overall survival and advanced tumor stage in ccRCC patients. Biological experiments demonstrated that overexpression of SIRT4 significantly reduced the proliferation, migration and invasion ability of ccRCC cells. Conversely, downregulation of SIRT4 enhanced the proliferation, migration and invasion ability of ccRCC cells. CONCLUSIONS: These findings support that SIRT4 acts as a tumor suppressor in ccRCC and might be a novel biomarker and new therapeutic target for ccRCC.

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Pathologic T1 clear cell renal cell carcinoma: Insulin-like growth factor-I receptor expression and disease-specific survival

Cancer ◽

10.1002/cncr.20322 ◽

2004 ◽

Vol 100 (12) ◽

pp. 2577-2582 ◽

Cited By ~ 17

Author(s):

Alexander S. Parker ◽

John C. Cheville ◽

Michael L. Blute ◽

Todd Igel ◽

Christine M. Lohse ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Growth Factor ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Receptor Expression ◽

Disease Specific Survival ◽

Cell Renal Cell Carcinoma ◽

Factor I ◽

Disease Specific

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Downregulation of lncRNA ZNF582-AS1 due to DNA hypermethylation promotes clear cell renal cell carcinoma growth and metastasis by regulating the N(6)-methyladenosine modification of MT-RNR1

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01889-8 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Wuping Yang ◽

Kenan Zhang ◽

Lei Li ◽

Yawei Xu ◽

Kaifang Ma ◽

...

Keyword(s):

Dna Methylation ◽

Renal Cell Carcinoma ◽

Protein Expression ◽

Cell Carcinoma ◽

Clinical Significance ◽

Renal Cell ◽

Clear Cell ◽

Expression Level ◽

Cell Renal Cell Carcinoma ◽

Qrt Pcr

Abstract Background Emerging evidence confirms that lncRNAs (long non-coding RNAs) are potential biomarkers that play vital roles in tumors. ZNF582-AS1 is a novel lncRNA that serves as a potential prognostic marker of cancers. However, the specific clinical significance and molecular mechanism of ZNF582-AS1 in ccRCC (clear cell renal cell carcinoma) are unclear. Methods Expression level and clinical significance of ZNF582-AS1 were determined by TCGA-KIRC data and qRT-PCR results of 62 ccRCCs. DNA methylation status of ZNF582-AS1 promoter was examined by MSP, MassARRAY methylation and demethylation analysis. Gain-of-function experiments were conducted to investigate the biological roles of ZNF582-AS1 in the phenotype of ccRCC. The subcellular localization of ZNF582-AS1 was detected by RNA FISH. iTRAQ, RNA pull-down and RIP-qRT-PCR were used to identify the downstream targets of ZNF582-AS1. rRNA MeRIP-seq and MeRIP-qRT-PCR were utilized to examine the N(6)-methyladenosine modification status. Western blot and immunohistochemistry assays were used to determine the protein expression level. Results ZNF582-AS1 was downregulated in ccRCC, and decreased ZNF582-AS1 expression was significantly correlated with advanced tumor stage, higher pathological stage, distant metastasis and poor prognosis. Decreased ZNF582-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. ZNF582-AS1 overexpression inhibited cell proliferative, migratory and invasive ability, and increased cell apoptotic rate in vitro and in vivo. Mechanistically, we found that ZNF582-AS1 overexpression suppressed the N(6)-methyladenosine modification of MT-RNR1 by reducing rRNA adenine N(6)-methyltransferase A8K0B9 protein level, resulting in the decrease of MT-RNR1 expression, followed by the inhibition of MT-CO2 protein expression. Furthermore, MT-RNR1 overexpression reversed the decreased MT-CO2 expression and phenotype inhibition of ccRCC induced by increased ZNF582-AS1 expression. Conclusions This study demonstrates for the first time that ZNF582-AS1 functions as a tumor suppressor gene in ccRCC and ZNF582-AS1 may serve as a potential biomarker and therapeutic target of ccRCC.

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The Significance of INHBE Expression in the Cancer Cells of Clear-Cell Renal Cell Carcinoma

Urologia Internationalis ◽

10.1159/000518161 ◽

2021 ◽

pp. 1-11

Author(s):

Zi-Bin Xu ◽

Mei-Fu Gan ◽

Hong-Yuan Yu ◽

Li-Cai Mo ◽

Yu-Hui Xia ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Cancer Cells ◽

Renal Cell ◽

Tumor Tissue ◽

Transforming Growth Factor ◽

Clear Cell ◽

Tumor Promoter ◽

Sequencing Data ◽

Cell Renal Cell Carcinoma

Background: Activins and inhibins are structurally related dimeric glycoprotein hormones belonging to the transforming growth factor-β superfamily but whether they are also involved in malignancy is far from clear. No study has reported the expression of INHBE in kidney cancer. The purpose of this study was to examine the expressions of INHBE in the tumor tissue of patients with clear-cell renal cell carcinoma (ccRCC) and to explore the pathologic significance. Methods: The INHBE mRNA expression in the tumor tissue of ccRCC patients was analyzed by using RNA sequencing data from the TCGA database. To examine the expression of inhibin βE protein, 241 ccRCC patients were recruited and immunohistochemistry was performed on the tumor tissue of these patients along with 39 normal renal samples. The association between the inhibin βE expression level and patient’s clinicopathological indices was evaluated. Results: In the normal renal tissue, inhibin βE was found to be expressed mainly by renal tubular epithelial cells. In the tumor tissue, inhibin βE was expressed mainly in cancer cells. The expressions of INHBE mRNA and protein in the tumor tissue of ccRCC patients increased significantly compared with those in normal renal samples. There was a significant correlation between the level of inhibin βE in the tumor tissue and tumor grade. Patients with a lower inhibin βE expression in the tumor tissue were found to have a longer overall survival and disease-specific survival. Conclusions: INHBE might be involved in the pathogenesis of ccRCC and function as a tumor promoter.

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