Abstract
Renal cell carcinoma (RCC) is the most common primary malignancy of the kidney and one of the most lethal genitourinary malignancies. Clear-cell renal cell carcinoma (ccRCC) has an extremely poor prognosis because of a high potential for tumor growth, vascular invasion, metastasis and recurrence. Unfortunately, the mechanism of RCC growth and metastasis is not well understood. In this report, we for the first time demonstrated ubiquitin protein ligase E3C (UBE3C) as a driving factor for RCC growth and metastasis. UBE3C expression was increased in ccRCC tissues compared with adjacent normal tissues. ccRCC patients with high UBE3C protein expression in tumors were associated with significantly worse postoperative survival. Knockdown of UBE3C expression in ACHN cells inhibited cell proliferation, migrations and invasiveness in vitro while overexpression of UBE3C in 786-O cells exerted the opposite effects. UBE3C up-regulated β-catenin protein levels and promoted β-catenin nuclear accumulation, leading to the activation of the Wnt/β-catenin signal pathway in RCC cells. Collectively, these observations suggest that UBE3C plays an important role in RCC development and progression, and UBE3C may be a novel target for prevention and treatment of ccRCC.
Highlights
Renal cell carcinoma (RCC) arises primarily in the renal parenchyma, accounting for over 90% of kidney carcinomas, among which clear cell RCC represents the most common histological subtype [1]
ubiquitin protein ligase E3C (UBE3C) expression was increased in clear cell RCC (ccRCC) tissues compared with adjacent normal tissues. ccRCC patients with high UBE3C protein expression in tumors are associated with significantly worse postoperative survival
RCC is the most common primary malignancy of the kidney and one of the most lethal genitourinary malignancies [22]. ccRCC has an extremely poor prognosis because of a high potential for vascular invasion, metastasis and recurrence [23,24,25]. Despite this the mechanism of ccRCC growth and metastasis is not well understood, evidence has been presented to indicate that Wnt/β-catenin signaling pathway is critical for ccRCC growth and metastasis [12, 17]
Summary
Renal cell carcinoma (RCC) arises primarily in the renal parenchyma, accounting for over 90% of kidney carcinomas, among which clear cell RCC (ccRCC) represents the most common histological subtype [1]. RCC has the highest mortality rate of the genitourinary cancers andthe incidence of RCC has risen steadily, accounting for approximately 200,000 new cases globally, with a mortality rate of more than 100,000 patients annually[2]. For treatment of localized RCC disease, nephrectomy is effective, whereas advanced RCC is still highly lethal with a 5year survival rate of 53% [3]. Insight into molecular mechanisms and pathways altered during the development of RCC remains limited. Its elucidation will facilitate the identification of biomarkers for prognosis prediction and intervention.
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