Ovarian cancer (OC) is the leading cause of death among women with gynecologic malignant diseases, however, the molecular mechanism of ovarian cancer is not well defined. Previous studies have found that RNA binding protein Lin28A is a key factor of maintain the pluripotency of stem cells, and it is positively correlated with the degree of several cancers (breast, prostate, liver cancer, etc). Our previous study shows that Lin28A is highly expressed in OC tissues and is involved in the regulation of OC cell biological behavior. In this study, we confirmed that high expression of Lin28A promoted the survival, invasion, metastasis, and inhibited the apoptosis of OC cells. Lin28A interacts with Rho associated coiled-coil containing protein kinase2 (ROCK2) but not ROCK1 and upregulates the expression of ROCK2 in OC cells. The binding sites of each other were identified by truncated mutations and Immuno-precipitaion (IP) assay. After knock down of ROCK2 in cells with high expression of Lin28A, the survival, invasion, metastasis was significantly inhibited and early apoptosis was increased in OC cells and OC xenograft in nude mice. Our experimental data also showed that knock down of ROCK2 but not ROCK1 inhibited the invasion by decreasing the expression of N-cadherin, Slug, β-catenin and increasing ZO-1 expression. Simultaneously, knock down of ROCK2 induced cell apoptosis by increasing cleaved Caspase-9,cleaved Caspase-7, and cleaved Caspase-3. Taken together, Lin28A regulated the biological behaviors in OC cells through ROCK2 and the interaction of Lin28A/ROCK2 may be a new target for diagnosis and gene therapy of OC.

中文翻译：

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Lin28A / Rho相关的含有蛋白激酶2的卷曲螺旋的相互作用加速了卵巢癌的恶性程度。

卵巢癌（OC）是妇科恶性肿瘤女性的主要死亡原因，但是，卵巢癌的分子机制尚不明确。先前的研究发现，RNA结合蛋白Lin28A是维持干细胞多能性的关键因素，并且与几种癌症（乳腺癌，前列腺癌，肝癌等）的程度呈正相关。我们以前的研究表明，Lin28A在OC组织中高度表达，并参与OC细胞生物学行为的调节。在这项研究中，我们证实Lin28A的高表达促进了OC细胞的存活，侵袭，转移并抑制了其凋亡。Lin28A与Rho相关的含有蛋白激酶2（ROCK2）的卷曲螺旋相互作用，但不与ROCK1相互作用，并上调OC细胞中ROCK2的表达。彼此的结合位点通过截短突变和免疫沉淀（IP）分析来鉴定。在高表达Lin28A的细胞中敲除ROCK2后，裸鼠的OC细胞和OC异种移植物中的存活，侵袭，转移受到了明显的抑制，早期凋亡增加。我们的实验数据还表明，敲除ROCK2而不抑制ROCK1可以通过降低N-钙黏着蛋白，Slug，β-连环蛋白的表达并增加ZO-1的表达来抑制侵袭。同时，敲低ROCK2通过增加裂解的Caspase-9，裂解的Caspase-7和裂解的Caspase-3诱导细胞凋亡。总之，Lin28A通过ROCK2调控OC细胞的生物学行为，Lin28A / ROCK2的相互作用可能成为OC诊断和基因治疗的新目标。