长链非编码RNA Lnc-OvM在卵巢癌腹腔转移中的生物学功能及分子机制研究

Ovarian cancer is one of the most lethal gynecological malignancies, whose primary metastatic site is peritoneal cavity. However, the underlying molecular mechanisms for the peritoneal metastasis of ovarian cancer remain unelucidated. Therefore, it is imperative to identify key molecules responsible for the peritoneal metastasis of ovarian cancer, which is crucial to unravel the molecular pathogenesis of ovarian cancer and to develop new therapeutic options for ovarian cancer patients. We previously identified a novel long non-coding RNA Lnc-OvM, which was over-expressed in ovarian cancer cell lines with higher metastatic potential compared with those with lower metastatic potential. In clinical samples, Lnc-OvM expression was correlated with clinical staging and prognosis of ovarian cancer patients. Moreover, silencing of Lnc-OvM expression could significantly impair ovarian cancer metastasis both in vitro and in vivo. In this project, we aim to explore the molecular mechanisms underlying Lnc-OvM-mediated ovarian cancer metastasis as well as to clarify the potential application values of Lnc-OvM as a novel therapeutic target for ovarian cancer, which might lay theoretical foundations for the development of new treatment strategies for ovarian cancer patients.

卵巢癌是致死率最高的女性生殖系统肿瘤，其主要转移途径为腹腔转移。然而，目前卵巢癌腹腔转移分子机理尚未阐明。因此，探索卵巢癌腹腔转移关键分子机制对于揭示卵巢癌发生发展机理及探索卵巢癌治疗新策略至关重要。我们前期研究发现，长链非编码RNA分子Lnc-OvM在高转移潜能卵巢癌细胞系中表达显著高于低转移潜能卵巢癌细胞系，且在临床卵巢癌样本中，其表达水平与卵巢癌患者临床分期及预后密切相关。体内外研究发现，沉默Lnc-OvM分子能显著降低卵巢癌的腹腔转移能力。本项目拟在前期工作基础上，采用分子生物学方法从体内外水平系统研究长链非编码RNA分子Lnc-OvM在卵巢癌腹腔转移中的生物学功能，阐明其介导卵巢癌腹腔转移的分子机制，明确长链非编码RNA分子Lnc-OvM作为卵巢癌新型治疗靶标的潜在应用价值，为发展卵巢癌治疗新策略提供理论依据。

在该面上项目的资助下，我们开展了筛选和鉴定介导卵巢癌腹腔转移关键非编码长链RNA分子及相关分子机制的系统研究：我们以卵巢癌转移体内外模型为研究工具，综合应用分子细胞生物学、组织病理学、生物化学等技术手段，同时结合完备的临床患者信息，分析了长链非编码RNA分子Lnc-OvM在不同临床分期和病理分级的卵巢癌患者中的表达差异，并对其亚细胞定位进行了验证。进一步体内外功能实验证实，Lnc-OvM在介导卵巢癌腹腔转移过程中的重要生物学功能及其下游关键分子事件，探索了其在卵巢癌患者临床诊断和预后预测中的临床意义。