Metabolic Footprinting of a Clear Cell Renal Cell Carcinoma in Vitro Model for Human Kidney Cancer Detection

With the rapid development of biotechnology, long noncoding RNAs (lncRNAs) have exhibited good application prospects in the treatment of cancer, and they may become new treatment targets for cancer. This study aimed to explore lncRNAs in clear cell renal cell carcinoma (ccRCC). Differentially expressed lncRNAs in 54 pairs of ccRCC tissues and para-carcinoma tissues were analyzed in The Cancer Genome Atlas (TCGA), and the most significant lncRNAs were selected and verified in ccRCC tissues. We found that lncRNA LINC02747 was highly expressed in ccRCC (P < 0.001) and was closely related to high TNM stage (P = 0.006) and histological grade (P = 0.004) and poor prognosis of patients (P < 0.001). In vivo and in vitro experiments confirmed that LINC02747 could promote the proliferation of ccRCC cells. We also found that LINC02747 regulated the proliferation of RCC cells by adsorbing miR-608. Subsequent mechanistic research showed that miR-608 is downregulated in ccRCC (P < 0.001), and overexpression of miR-608 inbibited the proliferation of RCC cells. Moreover, we found that TFE3 is a direct target gene of miR-608. MiR-608 regulated the proliferation of RCC cells by inhibiting TFE3. In conclusion, LINC02747 upregulates the expression of TFE3 by adsorbing miR-608, ultimately promoting the proliferation of ccRCC cells. The above findings indicate that LINC02747 acts as an oncogene in ccRCC and may be developed as a molecular marker for the diagnosis and prognosis of ccRCC. The LINC02747/miR-608/TFE3 pathway may become a new therapeutic target for ccRCC.

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Targeting β2-Adrenergic Receptors Shows Therapeutical Benefits in Clear Cell Renal Cell Carcinoma from Von Hippel–Lindau Disease

Journal of Clinical Medicine ◽

10.3390/jcm9092740 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2740

Author(s):

Virginia Albiñana ◽

Eunate Gallardo-Vara ◽

Isabel de Rojas-P ◽

Lucia Recio-Poveda ◽

Tania Aguado ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Von Hippel Lindau ◽

Gene And Protein Expression ◽

Ici 118,551

Von Hippel–Lindau (VHL), is a rare autosomal dominant inherited cancer in which the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HB), CNS-HB, and clear cell renal cell carcinoma (ccRCC). ccRCC ranks third in terms of incidence and first in cause of death. Standard systemic therapies for VHL-ccRCC have shown limited response, with recurrent surgeries being the only effective treatment. Targeting of β2-adrenergic receptor (ADRB) has shown therapeutic antitumor benefits on VHL-retinal HB (clinical trial) and VHL-CNS HB (in vitro). Therefore, the in vitro and in vivo antitumor benefits of propranolol (ADRB-1,2 antagonist) and ICI-118,551 (ADRB-2 antagonist) on VHL−/− ccRCC primary cultures and 786-O tumor cell lines have been addressed. Propranolol and ICI-118,551 activated apoptosis inhibited gene and protein expression of HIF-2α, CAIX, and VEGF, and impaired partially the nuclear internalization of HIF-2α and NFĸB/p65. Moreover, propranolol and ICI-118,551 reduced tumor growth on two in vivo xenografts. Finally, ccRCC patients receiving propranolol as off-label treatment have shown a positive therapeutic response for two years on average. In summary, propranolol and ICI-118,551 have shown antitumor benefits in VHL-derived ccRCC, and since ccRCCs comprise 63% of the total RCCs, targeting ADRB2 becomes a promising drug for VHL and other non-VHL tumors.

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Comprehensive analysis of copy number variance and sensitivity to common targeted therapy in clear cell renal cell carcinoma: In silico analysis with in vitro validation

Cancer Medicine ◽

10.1002/cam4.3281 ◽

2020 ◽

Vol 9 (16) ◽

pp. 6020-6029 ◽

Cited By ~ 1

Author(s):

Yuqing Li ◽

Yanyun Shen ◽

Zhidong Zhu ◽

Hui Wen ◽

Chenchen Feng

Keyword(s):

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Renal Cell ◽

Copy Number ◽

Clear Cell ◽

In Silico Analysis ◽

Comprehensive Analysis ◽

Cell Renal Cell Carcinoma ◽

Silico Analysis

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IMPA2 Downregulation Enhances mTORC1 Activity and Restrains Autophagy Initiation in Metastatic Clear Cell Renal Cell Carcinoma

Journal of Clinical Medicine ◽

10.3390/jcm9040956 ◽

2020 ◽

Vol 9 (4) ◽

pp. 956 ◽

Cited By ~ 1

Author(s):

Chia-Hao Kuei ◽

Hui-Yu Lin ◽

Hsun-Hua Lee ◽

Che-Hsuan Lin ◽

Jing-Quan Zheng ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Mtor Inhibitors ◽

Gene Set Enrichment Analysis ◽

Cellular Migration ◽

Cell Renal Cell Carcinoma ◽

Gene Set

Although mTOR inhibitors have been approved as first-line therapy for treating metastatic clear cell renal cell carcinoma (ccRCC), the lack of useful markers reduces their therapeutic effectiveness. The objective of this study was to estimate if inositol monophosphatase 2 (IMPA2) downregulation refers to a favorable outcome in metastatic ccRCC receiving mTOR inhibitor treatment. Gene set enrichment analysis predicted a significant activation of mTORC1 in the metastatic ccRCC with IMPA2 downregulation. Transcriptional profiling of IMPA2 and mTORC1-related gene set revealed significantly inverse correlation in ccRCC tissues. Whereas the enforced expression of exogenous IMPA2 inhibited the phosphorylation of Akt/mTORC1, artificially silencing IMPA2 led to increased phosphorylation of Akt/mTORC1 in ccRCC cells. The pharmaceutical inhibition of mTORC1 activity by rapamycin reinforced autophagy initiation but suppressed the cellular migration and lung metastatic abilities of IMPA2-silenced ccRCC cells. In contrast, blocking autophagosome formation with 3-methyladenine rescued the mitigated metastatic potential in vitro and in vivo in IMPA2-overexpressing ccRCC cells. Our findings indicated that IMPA2 downregulation negatively activates mTORC1 activity and could be a biomarker for guiding the use of mTOR inhibitors or autophagy inducers to combat metastatic ccRCC in the clinic.

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LncRNA-LET inhibits cell growth of clear cell renal cell carcinoma by regulating miR-373-3p

Cancer Cell International ◽

10.1186/s12935-019-1008-6 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Zhuo Ye ◽

Jiachen Duan ◽

Lihui Wang ◽

Yanli Ji ◽

Baoping Qiao

Keyword(s):

Cell Cycle ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Tissue Inhibitor Of Metalloproteinase ◽

Luciferase Reporter ◽

Cell Renal Cell Carcinoma

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype with a poor prognosis. LncRNA-LET is a long non-coding RNA (lncRNA) that is down-regulated in ccRCC tissues. However, its role in ccRCC development and progress is unclear. Methods LncRNA-LET expression was detected in ccRCC tissues and ccRCC cells using quantitative real-time PCR. The overexpression and knockdown experiments were performed in ccRCC cells and xenograft mouse model to evaluate role of lncRNA-LET. Cell cycle, apoptosis and JC-1 assays were conducted via flow cytometer. The protein levels were measured through western blot analysis and the interaction between lncRNA-LET and miR-373-3p was identified via luciferase reporter assay. Results LncRNA-LET expression was lower in ccRCC tissues than that in the matched adjacent non-tumor tissues (n = 16). In vitro, lncRNA-LET overexpression induced cell cycle arrest, promoted apoptosis and impaired mitochondrial membrane potential, whereas its knockdown exerted opposite effects. Moreover, we noted that lncRNA-LET may act as a target for oncomiR miR-373-3p. In contrast to lncRNA-LET, miR-373-3p expression was higher in ccRCC tissues. The binding between lncRNA-LET and miR-373-3p was validated. Two downstream targets of miR-373-3p, Dickkopf-1 (DKK1) and tissue inhibitor of metalloproteinase-2 (TIMP2), were positively regulated by lncRNA-LET in ccRCC cells. MiR-373-3p mimics reduced lncRNA-LET-induced up-regulation of DKK1 and TIMP2 levels, and attenuated lncRNA-LET-mediated anti-tumor effects in ccRCC cells. In vivo, lncRNA-LET suppressed the growth of ccRCC xenograft tumors. Conclusion These findings indicate that lncRNA-LET plays a tumor suppressive role in ccRCC by regulating miR-373-3p.

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PD33-11 METABOLIC MODULATION WITH DICHLOROACETATE REVERSES THE WARBURG EFFECT AND REDUCES THE GROWTH OF CLEAR CELL RENAL CELL CARCINOMA IN VITRO AND IN VIVO

The Journal of Urology ◽

10.1016/j.juro.2015.02.2109 ◽

2015 ◽

Vol 193 (4S) ◽

Author(s):

Adam Kinnaird ◽

Peter Dromparis ◽

Roxane Paulin ◽

Bruno Saleme ◽

Trevor Stenson ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Warburg Effect ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Metabolic Modulation ◽

The Warburg Effect

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MEIS1 inhibits clear cell renal cell carcinoma cells proliferation and in vitro invasion or migration

BMC Cancer ◽

10.1186/s12885-017-3155-2 ◽

2017 ◽

Vol 17 (1) ◽

Cited By ~ 13

Author(s):

Jie Zhu ◽

Liang Cui ◽

Axiang Xu ◽

Xiaotao Yin ◽

Fanglong Li ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Carcinoma Cells ◽

Cell Renal Cell Carcinoma ◽

In Vitro Invasion

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Knockdown of the nucleosome binding protein 1 inhibits the growth and invasion of clear cell renal cell carcinoma cells in vitro and in vivo

Journal of Experimental & Clinical Cancer Research ◽

10.1186/1756-9966-31-22 ◽

2012 ◽

Vol 31 (1) ◽

pp. 22 ◽

Cited By ~ 22

Author(s):

Shi-Qi Ji ◽

Lin Yao ◽

Xiao-Yu Zhang ◽

Xue-Song Li ◽

Li-Qun Zhou

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Binding Protein ◽

Carcinoma Cells ◽

Cell Renal Cell Carcinoma ◽

Nucleosome Binding

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G6PD upregulates Cyclin E1 and MMP9 to promote clear cell renal cell carcinoma progression

10.21203/rs.3.rs-110205/v1 ◽

2020 ◽

Author(s):

Zhe Yang ◽

Qiao Zhang ◽

Yueli Ni ◽

Qiaoqiao Han ◽

Shujie Wang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Renal Cell ◽

Poor Prognosis ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Cyclin E1 ◽

Mmp9 Expression

Abstract Background: Clear cell renal cell carcinoma (ccRCC) is a cell metabolic disease with high metastasis rate and poor prognosis. Our previous studies demonstrate that glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the pentose phosphate pathway, is highly expressed in ccRCC and predicts poor outcomes of ccRCC patients. The aims of this study were to confirm the oncogenic role of G6PD in ccRCC and unravels novel mechanisms involving Cyclin E1 and MMP9 in G6PD-mediated ccRCC progression. Methods: Real-time RT-PCR, Western blot and immunohistochemistry were used to determine the expression patterns of G6PD, Cyclin E1 and MMP9 in ccRCC. TCGA dataset mining was used to identify Cyclin E1 and MMP9 correlations with G6PD expression, relationships between clinicopathological characteristics of ccRCC and the genes of interest, as well as the prognosis of ccRCC patients. The role of G6PD in ccRCC progression and the regulatory effect of G6PD on Cyclin E1 and MMP9 expression were investigated by using a series of cytological function assays in vitro. To verify this mechanism in vivo, xenografted mice models were established. Results: G6PD, Cyclin E1 and MMP9 were overexpressed and positively correlated in ccRCC, and they were associated with poor prognosis of ccRCC patients. Moreover, G6PD changed cell cycle dynamics, facilitated cells proliferation, promoted migration in vitro, and enhanced ccRCC development in vivo, more likely through enhancing Cyclin E1 and MMP9 expression. Conclusion: These findings present G6PD, Cyclin E1 and MMP9, which contribute to ccRCC progression, as novel biomarkers and potential therapeutic targets for ccRCC treatment.

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