Tong Wenxian, Yang Liu, Yu Qiang, Yao Jie, He Anbing
Department of Oncology, The Fifth Hospital of Wuhan.
Department of Cancer Biotherapy Center, Hubei Cancer Hospital, Wuhan.
Onco Targets Ther. 2017 Feb 27;10:1227-1235. doi: 10.2147/OTT.S125185. eCollection 2017.
At present, a large number of long noncoding RNAs (lncRNAs) from the human genome have been discovered. Meanwhile, emerging evidence has indicated that lncRNAs could play a critical role in the regulation of cellular processes such as cancer progression and metastasis. However, the functions of some new lncRNAs in the complex transcriptional process are mostly unknown at present. Existing studies suggest that loss of WW domain-containing oxidoreductase () expression is linked with poor prognosis in numerous cancers, including epithelial ovarian cancer (EOC). However, the functional role of its antisense transcript RP11-190D6.2 is not clear to date. In this study, antisense transcript RP11-190D6.2 was analyzed specifically in EOC cells using real-time polymerase chain reaction and gain-/loss-of-function studies. We found that RP11-190D6.2 expression was positively correlated with expression. The RP11-190D6.2 expression was markedly downregulated in tumor tissues compared with normal tissues, but the RP11-190D6.2 expression was significantly downregu-lated in four EOC cell lines compared with human ovarian surface epithelial cell line. RP11-190D6.2 overexpression resulted in the increase of expression, whereas its knockdown led to the decrease of expression. We also found that RP11-190D6.2 was restored by 5-aza-2'-deoxycytidine treatment in EOC. In addition, the RP11-190D6.2 overexpression and knockdown experiments revealed that RP11-190D6.2 overexpression inhibited proliferation, migration, and invasion abilities in HO8910-PM cells, whereas RP11-190D6.2 knockdown in HEY-A8 cells had the opposite effect. The analyses in EOC implicate that RP11-190D6.2 may play a pivotal role in the regulation of tumor metastasis, suggesting that RP11-190D6.2 may serve as a potential biomarker and therapeutic target for EOC.
目前，人类基因组中大量的长链非编码RNA（lncRNAs）已被发现。与此同时，新出现的证据表明，lncRNAs在癌症进展和转移等细胞过程的调控中可能发挥关键作用。然而，目前一些新的lncRNAs在复杂转录过程中的功能大多仍不清楚。现有研究表明，含WW结构域的氧化还原酶（）表达缺失与包括上皮性卵巢癌（EOC）在内的多种癌症的不良预后相关。然而，其反义转录本RP11-190D6.2的功能作用迄今尚不清楚。在本研究中，使用实时聚合酶链反应以及功能获得/缺失研究，对EOC细胞中的反义转录本RP11-190D6.2进行了专门分析。我们发现RP11-190D6.2的表达与的表达呈正相关。与正常组织相比，肿瘤组织中RP11-190D6.2的表达明显下调，但与人类卵巢表面上皮细胞系相比，四种EOC细胞系中RP11-190D6.2的表达显著下调。RP11-190D6.2的过表达导致表达增加，而其敲低则导致表达减少。我们还发现，5-氮杂-2'-脱氧胞苷处理可使EOC中的RP11-190D6.2恢复。此外，RP11-190D6.2的过表达和敲低实验表明，RP11-190D6.2的过表达抑制了HO8910-PM细胞的增殖、迁移和侵袭能力，而在HEY-A8细胞中敲低RP11-190D6.2则产生相反的效果。对EOC的分析表明，RP11-190D6.2可能在肿瘤转移的调控中起关键作用，这表明RP11-190D6.2可能作为EOC的潜在生物标志物和治疗靶点。
