Abstract
Aldolase A (fructose-bisphosphate aldolaseA, ALDOA) is a glycolytic enzyme that catalyzes reversible conversion of fructose‑1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. ALDOA has been revealed to be related with many carcinomas, but its expression and function in renal cell carcinoma (RCC) remain unknown. This study aimed to detect expression of ALDOA in human RCC tissue samples and to explore its function in RCC cell lines. Reverse transcription-polymerase chain reaction was used to quantify ALDOA in human RCC samples. A total of 139RCC tissue samples obtained after surgery were analyzed in tissue microarray for ALDOA immunohistochemistry-based protein expression. Assays for cell cycle, viability, migration, and invasion were performed to assess phenotypic changes in RCC cells after ALDOA knockdown by small interfering RNA-mediated gene silencing approach and ALDOA upregulation by overexpression plasmids. Western blot analysis was used to identify alterations in markers for epithelial-mesenchymal transition (EMT), which affects metastasis and the Wnt/β‑catenin signaling pathway that influences RCC cell growth. ALDOA was upregulated in RCC samples and RCC cell lines (P<0.01). Expression of ALDOA was significantly associated with metastasis (P=0.020) and survival (P=0.0341). Downregulation of ALDOA suppressed proliferation (P<0.05) by triggering G0/G1 cell cycle arrest (P<0.05) and also inhibited migration (P<0.05) and invasion (P<0.01). Upregulation of ALDOA promoted proliferation (P<0.05) and enhanced migration (P<0.001) and invasion (P<0.001). Low expression of ALDOA could reverse EMT and inactivate the Wnt/β‑catenin signaling pathway. Our data revealed that ALDOA functions as a tumor promoter, plays a prominent role in proliferation, migration, and invasion of RCC cells with high expression, and may promote EMT and activate the Wnt/β‑catenin signaling pathway.
Highlights
Renal cell carcinoma (RCC) is commonly diagnosed in urological malignant tumors
In patients with localized RCC, probability of metastasis remains as high as 40%; and tumor metastasis of these patients results in a median survival time of approximately 6‐12 months, with a 5-year survival rate of 9% [19]
We first used reverse transcription-polymerase chain reaction (RT‐PCR) to confirm high expression of ALDOA in RCC tissues and cells in comparison with normal ones, suggesting that increased expression of ALDOA may be related to the occurrence of RCC
Summary
Renal cell carcinoma (RCC) is commonly diagnosed in urological malignant tumors. In 2016, the American Cancer Society estimated that the number of new kidney cancer cases would reach almost 62,000 in the United States, accounting for 1 in 20 new diagnoses in men and 3% for women [1]. An estimated 14,000 Americans will succumb to kidney cancer this year. In China, RCC is one of the common diseases in urology. Projected age-standardized incidence rate (per 100,000) of kidney cancer reaches 2.4 in males and 1.0 in females [2]. Scientists have not identified exact causes of RCC occurrence, accumulating evidence suggests that obesity, hypertension, smoking, alcohol, occupational exposure to trichloroethylene, and genetic factors are risk factors for this disease [3]
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