Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China.
J Surg Oncol. 2012 Jun 15;105(8):841-7. doi: 10.1002/jso.23013. Epub 2011 Dec 27.
Forkhead box O-class 1 (FOXO1), a putative tumor suppressor, is dysregulated in many cancers. Our study aims to reveal the underlying functions and regulation mechanisms of FOXO1 in renal cell carcinoma (RCC).
The clinical significance of FOXO1 expression in surgically resected specimens was assessed by immunohistochemistry. The siRNAs targeted FOXO1 and miR-27a inhibitor were transfected into RCC cells. QRT-PCR, Western blot, and cell proliferation assay were used to assess the expression and function of FOXO1 and miR-27a.
The positive immunostaining for FOXO1 was low in 51 RCC samples compared with 15 normal kidney tissues. And the expression of FOXO1 was related with RCC subtypes and the grade and stage in clear cell RCC (cRCC) (P < 0.05). Inhibition of FOXO1 promoted proliferation of 769-P cells. However, upregulation of FOXO1 by miR-27a inhibitor was accompanied by the anti-proliferative effect in cells of 786-O and Caki-1. Furthermore, the expression of FOXO1 mRNA and miR-27a had inverse relation in eight cRCC samples.
Reduced expression of FOXO1 is common in RCC and a potentially suitable marker of different histological subtypes and prognosis of cRCC. Increasing expression of FOXO1 by the miR-27a inhibitor could prevent cell growth.
叉头框 O 类 1（FOXO1）是一种潜在的肿瘤抑制因子，在许多癌症中失调。我们的研究旨在揭示 FOXO1 在肾细胞癌（RCC）中的潜在功能和调控机制。
采用免疫组织化学法检测手术切除标本中 FOXO1 的表达情况。将靶向 FOXO1 的 siRNA 和 miR-27a 抑制剂转染到 RCC 细胞中。采用 QRT-PCR、Western blot 和细胞增殖实验检测 FOXO1 和 miR-27a 的表达和功能。
与 15 例正常肾组织相比，51 例 RCC 样本中 FOXO1 的阳性免疫染色较低。并且，在透明细胞 RCC（cRCC）中，FOXO1 的表达与 RCC 亚型、分级和分期有关（P<0.05）。抑制 FOXO1 促进了 769-P 细胞的增殖。然而，miR-27a 抑制剂上调 FOXO1 的表达伴随着 786-O 和 Caki-1 细胞的抗增殖作用。此外，在 8 例 cRCC 样本中，FOXO1 mRNA 和 miR-27a 的表达呈负相关。
RCC 中 FOXO1 的表达降低较为常见，是不同组织学亚型和 cRCC 预后的潜在合适标志物。miR-27a 抑制剂增加 FOXO1 的表达可阻止细胞生长。
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