功能未知的lncRNA：RP5-1148A21.3调控卵巢上皮癌侵袭转移的分子机制

RP5-1148A21.3, an unclear function lncRNA, was specially over-expressed in malignant epithelial ovarian carcinoma. Our previous studies found that: The expression of RP5-1148A21.3 was more highly expressed in III/IV ovarian tumor tissue, suggest it may be related with the invasion of ovarian carcinoma. RP5-1148A21.3 silencing could reduce the invasion ability of epithelial ovarian cancer cell. The mechanism may be related to the recruitment of P300 to regulate PTP4A1 expression by RP5-1148A21.3.In this study, we will further investigate the bioinformatics characteristics of RP5-1148A21.3 and detect the expression of RP5-1148A21.3 in ovarian tissue. The relationship between the RP5-1148A21.3 and the malignancy of ovarian cancer will be investigated on clinical samples and animal experiments. We will demonstrate the mechanism of RP5-1148A21.3 induced invasion and metastasis of epithelial ovarian cancer with overexpression and suppression techniques at the cellular level. Furtherly, We will investigate effect of RP5-1148A21.3 on growth of subcutaneous implantation tumor in nude mice by establishment of human ovarian epithelial cancer subcutaneous xenograft model. This study which will potentially provide a new target for the prevention and treatment of ovarian carcinoma.

RP5-1148A21.3（RP5）是采用芯片技术筛选在恶性卵巢上皮癌组织中表达显著上调的、功能未知的一条lncRNA。关于RP5目前尚未见文献报道。前期发现RP5在III/IV期卵巢上皮癌表达水平更高，提示与侵袭转移相关，进一步沉默RP5证实其可显著降低卵巢上皮癌细胞侵袭能力，其机制可能与招募p300调控PTP4A1表达有关。本项目拟在已有研究基础上进一步探讨RP5的生物学特征；临床与动物实验评估RP5与卵巢癌恶性程度、PTP4A1表达之间的相关性；采用基因过表达与敲低策略，明确RP5对卵巢上皮癌细胞侵袭转移的影响；并通过挽救实验策略及RIP、RNA pull-down等技术深入探讨RP5通过招募p300调控PTP4A1的具体分子机制。研究有源头创新性，可为卵巢上皮癌的防治提供干预新靶标。

lncRP5是我们通过lncRNA芯片筛选发现的，在恶性卵巢上皮癌组织中表达显著上调的lncRNA。本项目从体外细胞实验、荷瘤动物模型以及临床样本三个层次阐述RP5促进卵巢上皮癌侵袭的生物学功能；临床与动物实验评估RP5与卵巢癌恶性程度、PTP4A1表达之间的相关性，提出了lncRP5/miR-545-5p/PTP4A1调控轴在卵巢癌发生发展的作用,明确了lncRP5对卵巢上皮癌细胞侵袭转移的影响。