Deregulation of energetic metabolism in the clear cell renal cell carcinoma: A multiple pathway analysis based on microarray profiling

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most frequent type of kidney cancer. In order to better understand the biology of ccRCC, we accomplished the gene profiling of fresh tissue specimens from 11 patients with the renal tumors (9 ccRCCs, 1 oncocytoma and 1 renal B-lymphoma), in which the tumor-related data were compared to the paired healthy kidney tissues from the same patients. All ccRCCs exhibited a considerably elevated transcription of the gene coding for carbonic anhydrase IX (CAIX). Moreover, the ccRCC tumors consistently displayed increased expression of genes encoding the glycolytic pathway enzymes, e.g. hexokinase II (HK2) and lactate dehydrogenase A (LDHA) and a decreased expression of genes for the mitochondrial electron transport chain components, indicating an overall reprogramming of the energetic metabolism in this tumor type. This appears to be accompanied by altered expression of the genes of the pH regulating machinery, including ion and lactate transporters. Immunohistochemical staining of tumor tissue sections confirmed the increased expression of CAIX, HK2 and LDHA in ccRCC, validating the microarray data and supporting their potential as the energetic metabolism-related biomarkers of the ccRCC.

HIF prolyl hydroxylase PHD3 regulates translational machinery and glucose metabolism in clear cell renal cell carcinoma

“…Moreover, ccRCC tumours and derived cells lines have been shown to consistently display increased expression of the glycolytic pathway enzymes [4, 6, 37]. Interestingly, major proteome-level changes affected by PHD3 depletion were found in glucose metabolic pathway.…”

LDHA promotes tumor metastasis by facilitating epithelial-mesenchymal transition in renal cell carcinoma

“…Recent studies demonstrated that the Warburg effect serve an important role in tumor development and progression (7,8). Numerous studies reported that the expression of genes involved in energetic metabolism displayed heterogeneity in RCC, suggesting that the Warburg effect may participate in the development of RCC (9,10). However, the function and mechanism of the Warburg effect in RCC remains unknown.…”

Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell Carcinoma

“…Many studies in tumors confirms the view that target LDHA may represent novel therapeutic strategies for controlling tumor growth [9,10,12,[15][16][17] . Meanwhile, previous reports showed that the expression of LDHA was abnormality abundant in RCC than that in matched normal renal tissue [2,20] , which promotes us to determine the function of LDHA on renal cancer development. Consistent with previous theory, our results showed that LDHA silence with siRNA inhibit cell growth and induce cell apoptosis.…”

“…Renal cell carcinoma (RCC) is still ranked as the most common malignant renal tumor [1][2][3] . It is responsible for more than 90% of all renal tumors, and the disease accounts for approximately 3% of all cancers worldwide [4][5][6] .…”

“…In pancreatic cancer, reduced c-myc-LDHA signaling resulted in decreased tumor growth and metastasis [18] . In clear cell RCC, previous studies showed that the expression of LDHA is upregulated compared to normal renal tissue [20] , and furthermore, many studies have the view that targeting the glucose metabolism may represent an interesting tool to improve the efficacy of specific immunotherapeutic approaches [2,21] . However, the molecular function of LDHA in RCC, and its possible mechanism, remains unclear.…”