Lin Xiaojing, Tang Xiaoyan, Zheng Tingting, Qiu Junjun, Hua Keqin
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, P.R. China.
Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
J Cancer. 2019 Apr 25;10(8):1930-1940. doi: 10.7150/jca.29057. eCollection 2019.
Although accumulating evidence suggests that long non-coding RNAs (lncRNAs) are critical determinants of ovarian cancer development and progression, reports of metastasis-associated lncRNAs are limited. Here, we focused on NONHSAT076754 and explored its expression level, clinical value, biological behavior and molecular basis in epithelial ovarian cancer (EOC) metastasis. The results showed that NONHSAT076754 expression was increased in EOC tissues and cell lines and that this expression was closely related with FIGO stage, high tumor grade and lymph node metastasis. Furthermore, NONHSAT076754 knockdown markedly inhibited EOC cell migration and invasion . Consistently, the data from both the bioluminescence imaging and tumor dissection revealed that depletion of NONHSAT076754 reduced EOC metastasis. Mechanically, the pro-metastatic activities of NONHSAT076754 were partially regulated by PTEN and HTATIP2. Further rescue assays validated that knockdown of HTATIP2 remarkably reversed NONHSAT076754 silencer-induced inhibition of EOC cell metastasis. These data indicate that NONHSAT076754 is a vital regulator of EOC metastasis, laying the foundation for lncRNA-based clinical management of EOC aggressiveness and metastasis.
尽管越来越多的证据表明长链非编码RNA（lncRNAs）是卵巢癌发生和发展的关键决定因素，但关于转移相关lncRNAs的报道却很有限。在此，我们聚焦于NONHSAT076754，并探究其在上皮性卵巢癌（EOC）转移中的表达水平、临床价值、生物学行为及分子基础。结果显示，NONHSAT076754在EOC组织和细胞系中的表达增加，且这种表达与国际妇产科联盟（FIGO）分期、高肿瘤分级及淋巴结转移密切相关。此外，敲低NONHSAT076754显著抑制了EOC细胞的迁移和侵袭。同样，生物发光成像和肿瘤解剖的数据均显示，敲除NONHSAT076754可减少EOC转移。从机制上讲，NONHSAT076754的促转移活性部分受PTEN和HTATIP2调控。进一步的挽救实验证实，敲低HTATIP2可显著逆转NONHSAT076754沉默诱导的EOC细胞转移抑制。这些数据表明，NONHSAT076754是EOC转移的重要调节因子，为基于lncRNA的EOC侵袭性和转移的临床管理奠定了基础。
