Department of Gynecology and Obstetrics, Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, Liaoning Province, China.
Department of Gynecology and Obstetrics, General Hospital of Northern Theater Command, Shenyang, 110016, Liaoning Province, China.
J Ovarian Res. 2020 Jun 17;13(1):72. doi: 10.1186/s13048-020-00672-1.
Ovarian cancer (OC) is one of the most common malignant tumors in the world. The prognosis of OC remains poor due to the advanced stage and distant metastasis at the time of diagnosis. Recently, a novel lncRNA, THOR (testis-associated highly conserved oncogenic long non-coding RNA), was characterized in human cancers and shown to exhibit an oncogenic role. However, the role of THOR in OC remains unclear.
RT-PCR and western blot analysis were used to detect the expression of THOR, p-STAT3 and IL-6. The impact of THOR on OC proliferation, metastasis and self-renewal was investigated in vitro and in vivo. The prognostic value of THOR was determined in OC patient cohorts.
In this study, our results find that THOR is markedly upregulated in human OC tissues and predicts the poor prognosis of OC patients. Functional studies have revealed that knockdown of THOR inhibits the growth, metastasis and self-renewal of OC cells. Mechanistically, THOR drives OC cell progression via the IL-6/STAT3 signaling. Moreover, the specific STAT3 inhibitor S3I-201 or IL-6R inhibitor tocilizumab diminish the discrepancy in the growth, metastatic and self-renewal capacity between THOR-silenced OC cells and control cells, which further confirm that IL-6/STAT3 is required in THOR-driven OC cells progression.
Our findings reveal that THOR could promote OC cells growth, metastasis and self-renewal by activating IL-6/STAT3 signaling and may be a good predictive factor and therapeutic target.
卵巢癌（OC）是世界上最常见的恶性肿瘤之一。由于诊断时已处于晚期和远处转移，OC 的预后仍然很差。最近，一种新型 lncRNA，THOR（睾丸相关高度保守致癌长非编码 RNA），在人类癌症中被表征，并表现出致癌作用。然而，THOR 在 OC 中的作用尚不清楚。
使用 RT-PCR 和 Western blot 分析检测 THOR、p-STAT3 和 IL-6 的表达。在体外和体内研究了 THOR 对 OC 增殖、转移和自我更新的影响。在 OC 患者队列中确定了 THOR 的预后价值。
在这项研究中，我们的结果发现 THOR 在人 OC 组织中明显上调，并预测 OC 患者的预后不良。功能研究表明，THOR 的敲低抑制 OC 细胞的生长、转移和自我更新。机制上，THOR 通过 IL-6/STAT3 信号驱动 OC 细胞进展。此外，特异性 STAT3 抑制剂 S3I-201 或 IL-6R 抑制剂托珠单抗可减少 THOR 沉默的 OC 细胞与对照细胞之间在生长、转移和自我更新能力上的差异，这进一步证实了 IL-6/STAT3 在 THOR 驱动的 OC 细胞进展中是必需的。
我们的研究结果表明，THOR 通过激活 IL-6/STAT3 信号促进 OC 细胞的生长、转移和自我更新，可能是一个良好的预测因子和治疗靶点。
