Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
Neoplasma. 2022 Jan;69(1):113-122. doi: 10.4149/neo_2021_210607N762. Epub 2021 Nov 30.
Previous studies identified an association of low-density lipoprotein (LDL) levels and LDL receptor (LDLR) with renal cell carcinoma (RCC) development. This study investigated the expression and roles of LDLR in RCC. LDLR expression was examined in clear cell RCC (ccRCC) and adjacent normal kidney tissues, and its clinicopathological significance was analyzed. The role of LDLR in RCC cell proliferation, cell cycle, and invasion were assessed in RCC cells with LDLR stable knockdown. LDLR expression was higher in ccRCC tissues than in normal kidney tissues and increased with RCC progression. LDLR knockdown in RCC cells inhibited cell growth, migration and invasion, and induced G1/S cell cycle arrest. We identified an interaction between LDLR and EGFR, and EGFR signaling protein expression was reduced after LDLR knockdown. Our findings reveal that LDLR plays an important role in RCC carcinogenesis, suggesting that LDL and LDLR might be potential targets for therapeutic intervention in RCC.
先前的研究表明，低密度脂蛋白（LDL）水平和 LDL 受体（LDLR）与肾细胞癌（RCC）的发展有关。本研究探讨了 LDLR 在 RCC 中的表达和作用。检测了透明细胞 RCC（ccRCC）和相邻正常肾组织中 LDLR 的表达，并分析了其临床病理意义。通过 LDLR 稳定敲低的 RCC 细胞评估 LDLR 在 RCC 细胞增殖、细胞周期和侵袭中的作用。与正常肾组织相比，ccRCC 组织中 LDLR 的表达更高，并且随着 RCC 的进展而增加。LDLR 敲低可抑制 RCC 细胞的生长、迁移和侵袭，并诱导 G1/S 细胞周期停滞。我们发现 LDLR 与 EGFR 之间存在相互作用，并且 LDLR 敲低后 EGFR 信号蛋白表达减少。我们的研究结果表明，LDLR 在 RCC 发生发展中起重要作用，提示 LDL 和 LDLR 可能是 RCC 治疗干预的潜在靶点。
