He Wang, Zhong Guangzheng, Wang Pei, Jiang Chun, Jiang Ning, Huang Jian
Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, P.R. China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, P.R. China.
Oncol Lett. 2019 Jan;17(1):103-112. doi: 10.3892/ol.2018.9624. Epub 2018 Oct 26.
Long noncoding RNA FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) dysregulation associates with multiple types of human cancer. However, the biological functions of FENDRR in renal cell carcinoma are unresolved. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the expression level of FENDRR in renal cell carcinoma tissues. An RNA interference assay and ectopic expression experiments were conducted to evaluate the effects of FENDRR on cell proliferation, migration, invasion and colony formation . RNA immunoprecipitation was conducted to identify proteins associated with FENDRR. It was observed that FENDRR is frequently downregulated in renal cell carcinoma and overexpression of FENDRR attenuated proliferation, migration, invasion and colony growth of renal carcinoma cells. Conversely, knockdown of FENDRR promotes proliferation and invasiveness of renal carcinoma cells. Downregulation of FENDRR associates with poor prognosis of renal cell carcinoma. Mechanistically, it was identified that FENDRR may bind to Polycomb Repressive Complex 2 and lysin methyltransferase 2A histone modifying complexes. In summary, FENDRR acts as an tumor suppressor in renal cell carcinoma and may serve as a candidate target for gene therapy.
长链非编码RNA FOXF1相邻非编码发育调控RNA(FENDRR)失调与多种人类癌症相关。然而,FENDRR在肾细胞癌中的生物学功能尚未明确。采用逆转录定量聚合酶链反应(RT-qPCR)检测肾细胞癌组织中FENDRR的表达水平。进行RNA干扰试验和异位表达实验,以评估FENDRR对细胞增殖、迁移、侵袭和集落形成的影响。进行RNA免疫沉淀以鉴定与FENDRR相关的蛋白质。结果发现,FENDRR在肾细胞癌中经常下调,FENDRR的过表达减弱了肾癌细胞的增殖、迁移、侵袭和集落生长。相反,敲低FENDRR可促进肾癌细胞的增殖和侵袭性。FENDRR的下调与肾细胞癌的不良预后相关。机制上,已确定FENDRR可能与多梳抑制复合物2和赖氨酸甲基转移酶2A组蛋白修饰复合物结合。总之,FENDRR在肾细胞癌中起肿瘤抑制作用,可能作为基因治疗的候选靶点。