scholarly journals HMGCR inhibition stabilizes the glycolytic enzyme PKM2 to support the growth of renal cell carcinoma

PLoS Biology ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. e3001197
Author(s):  
Jiajun Huang ◽  
Xiaoyu Zhao ◽  
Xiang Li ◽  
Jiwei Peng ◽  
Weihao Yang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Development ◽  
Serum Levels ◽  
Glycolytic Enzyme ◽  
Hsp90 Expression ◽  
Cholesterol Biosynthetic Pathway ◽  
Underlying Mechanisms ◽  
Rate Limiting

Renal cell carcinoma (RCC) is responsible for most cases of the kidney cancer. Previous research showed that low serum levels of cholesterol level positively correlate with poorer RCC-specific survival outcomes. However, the underlying mechanisms and functional significance of the role of cholesterol in the development of RCC remain obscure. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) plays a pivotal role in RCC development as it is the key rate-limiting enzyme of the cholesterol biosynthetic pathway. In this study, we demonstrated that the inhibition of HMGCR could accelerate the development of RCC tumors by lactate accumulation and angiogenesis in animal models. We identified that the inhibition of HMGCR led to an increase in glycolysis via the regulated HSP90 expression levels, thus maintaining the levels of a glycolysis rate-limiting enzyme, pyruvate kinase M2 (PKM2). Based on these findings, we reversed the HMGCR inhibition-induced tumor growth acceleration in RCC xenograft mice by suppressing glycolysis. Furthermore, the coadministration of Shikonin, a potent PKM2 inhibitor, reverted the tumor development induced by the HMGCR signaling pathway.

AN INTERLEUKIN-10 PROMOTER POLYMORPHISM MAY INFLUENCE TUMOR DEVELOPMENT IN RENAL CELL CARCINOMA

2005 ◽  
Vol 173 (3) ◽  
pp. 709-712 ◽  
Author(s):  
E. HAVRANEK ◽  
W.M. HOWELL ◽  
H.M. FUSSELL ◽  
J.A. WHELAN ◽  
M.A. WHELAN ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Development ◽  
Interleukin 10 ◽  
Promoter Polymorphism

scholarly journals Alpha-1 blocker use increased risk of subsequent renal cell carcinoma: A nationwide population-based study in Taiwan

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242429
Author(s):  
Shian-Ying Sung ◽  
Trang Thi Huynh Le ◽  
Jin- Hua Chen ◽  
Teng-Fu Hsieh ◽  
Chia-Ling Hsieh
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Proportional Hazards ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Research Database ◽  
Antihypertensive Medications ◽  
Increased Risk ◽  
Underlying Mechanisms

Elevated Renal cell carcinoma (RCC) risk has been associated with the use of several antihypertensive medications but has not yet been elucidated in the populations prescribed alpha-1 blockers that are commonly used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS-BPH). The aim of the present study was to investigate the association between alpha-1 blocker use and the risk of developing RCC using a nationwide population-based database in Taiwan. Patients who were treated with alpha-1 blockers for at least 28 days were identified through the Taiwan National Health Insurance Research Database from 2000 to 2010. The unexposed participants were matched with the exposed cases according to age, sex, and index year at a ratio of 3:1. Cox proportional hazards regression, stratified by sex and comorbidities and adjusted for age, was performed to estimate hazard ratios (HRs) for the risk of subsequent RCC. Among 2,232,092 subjects, patients who received alpha-1 blocker treatment had a higher risk of RCC than the unexposed group. Taking into account hypertension and BPH, the adjusted HR was significantly higher in male alpha-1 blocker users who had no BPH and either the presence (HR: 1.63, 95% confidence interval [CI] = 1.22–2.18) or absence (HR: 2.31, 95% CI = 1.40–3.81) of hypertension than in men not receiving these drugs. Taken together, male alpha-1 blocker users who had no comorbidity of BPH exhibited an increased risk for developing RCC independent of hypertension. Further study is warranted to elucidate the underlying mechanisms of this association.

scholarly journals Identification of miR-21-5p and miR-210-3p serum levels as biomarkers for patients with papillary renal cell carcinoma: a multicenter analysis

2020 ◽  
Vol 9 (3) ◽  
pp. 1314-1322
Author(s):  
Charis Kalogirou ◽  
Jörg Ellinger ◽  
Glen Kristiansen ◽  
Georgios Hatzichristodoulou ◽  
Hubert Kübler ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Papillary Renal Cell Carcinoma ◽  
Serum Levels ◽  
Multicenter Analysis

Obesity and renal cell carcinoma: epidemiology, underlying mechanisms and management considerations

2009 ◽  
Vol 9 (7) ◽  
pp. 975-987 ◽  
Author(s):  
Zachary Klinghoffer ◽  
Brian Yang ◽  
Anil Kapoor ◽  
Jehonathan H Pinthus
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Underlying Mechanisms

scholarly journals Circulating biomarkers in renal cell carcinoma: the link between microRNAs and extracellular vesicles, where are we now?

2014 ◽  
Vol 1 (8) ◽  
pp. 84-98 ◽  
Author(s):  
Ana L Teixeira ◽  
Francisca Dias ◽  
Mónica Gomes ◽  
Mara Fernandes ◽  
Rui Medeiros
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Genetic Material ◽  
Tumor Development ◽  
Cell Communication ◽  
Bioactive Molecules ◽  
Screening Tests ◽  
Transcriptional Level ◽  
Incidence And Mortality

Renal cell carcinoma (RCC) is a lethal urological cancer, with incidence and mortality rates increasing by 2-3% per decade. The lack of   standard screening tests contributes to the fact that one-third of patients are diagnosed with locally invasive or metastatic disease. Moreover, 20-40% of RCC patients submitted to surgical nephrectomy will develop metastasis. MicroRNAs (miRNAs) are small non-coding RNAs responsible for gene regulation at a post-transcriptional level.  It is accepted that they are deregulated in cancer and can influence tumor development. Thus, miRNAs are promising RCC biomarkers, since they can be detected using non-invasive methods. They are highly stable and easier to quantify in circulating biofluids. The elevated miRNA stability in circulating samples may be the consequence of their capacity to circulate inside of extracellular microvesicles (EMVs), for example, the exosomes.  The EMVs are bilayered membrane vesicles secreted by all cell types. They can be released in the interstitial space or into circulating biofluids, which allows the travelling, binding and entrance of these vesicles in receptor cells. This type of cell communication can shuttle bioactive molecules between cells, allowing the horizontal transference of genetic material. In this review, we focus on circulating miRNAs (miR-210, miR-1233, miR-221, miR-15a, miR-451, miR-508, miR-378) in the biofluids of RCC patients and attempt to establish the diagnostic and prognostic accuracy, their synergic effects, and the pathways involved in RCC biology.

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