Sekino Yohei, Sakamoto Naoya, Goto Keisuke, Honma Ririno, Shigematsu Yoshinori, Quoc Thang Pham, Sentani Kazuhiro, Oue Naohide, Teishima Jun, Kawakami Fumi, Karam Jose A, Sircar Kanishka, Matsubara Akio, Yasui Wataru
Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Department of Urology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
BMC Cancer. 2018 Oct 4;18(1):952. doi: 10.1186/s12885-018-4863-y.
The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis in some cancers. However, the expression and biological role of T-UCRs in renal cell carcinoma (RCC) remain poorly understood. This study aimed to examine the expression and functional role of Uc.416 + A and analyze the association between Uc.416 + A and epithelial-to-mesenchymal transition in RCC.
Expression of Uc.416 + A in 35 RCC tissues, corresponding normal kidney tissues and 13 types of normal tissue samples was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). We performed a cell growth and migration assay in RCC cell line 786-O transfected with negative control and siRNA for Uc.416 + A. We evaluated the relation between Uc.416 + A and miR-153, which has a complimentary site of Uc.416 + A.
qRT-PCR analysis revealed that the expression of Uc.416 + A was higher in RCC tissues than that in corresponding normal kidney tissues. Inhibition of Uc.416 + A reduced cell growth and cell migration activity. There was an inverse correlation between Uc.416 + A and miR-153. Western blot analysis showed Uc.416 + A modulated E-cadherin, vimentin and snail. The expression of Uc.416 + A was positively associated with the expression of SNAI1, VIM and inversely associated with the expression of CDH1.
The expression of Uc.416 + A was upregulated in RCC and especially in RCC tissues with sarcomatoid change. Uc.416 + A promoted epithelial-to-mesenchymal transition through miR-153. These results suggest that Uc.416 + A may be a promising therapeutic target.
转录超保守区域（T-UCRs）是一类新型非编码RNA，在物种间绝对保守，且在某些癌症的致癌过程中发挥作用。然而，T-UCRs在肾细胞癌（RCC）中的表达及生物学作用仍知之甚少。本研究旨在检测Uc.416 + A的表达及其功能作用，并分析Uc.416 + A与RCC上皮-间质转化之间的关系。
采用定量逆转录-聚合酶链反应（qRT-PCR）检测35例RCC组织、相应正常肾组织及13种正常组织样本中Uc.416 + A的表达。对转染阴性对照和Uc.416 + A的小干扰RNA（siRNA）的RCC细胞系786-O进行细胞生长和迁移实验。评估Uc.416 + A与miR-153（其具有Uc.416 + A的互补位点）之间的关系。
qRT-PCR分析显示，Uc.416 + A在RCC组织中的表达高于相应正常肾组织。抑制Uc.416 + A可降低细胞生长和细胞迁移活性。Uc.416 + A与miR-153呈负相关。蛋白质免疫印迹分析显示，Uc.416 + A可调节E-钙黏蛋白、波形蛋白和蜗牛蛋白。Uc.416 + A的表达与SNAI1、VIM的表达呈正相关，与CDH1的表达呈负相关。
Uc.416 + A在RCC中，尤其是在伴有肉瘤样改变的RCC组织中表达上调。Uc.416 + A通过miR-153促进上皮-间质转化。这些结果表明，Uc.416 + A可能是一个有前景的治疗靶点。
