Long non-coding RNA THOR promotes Ovarian Cancer cells progression via IL-6/STAT3 pathway

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Overview of the signaling pathways involved in metastasis: An intriguing story-tale of the metastatic journey of ovarian cancer cells

“…Levels of IL-6 and p-STAT3 were noted to be suppressed in THOR-knockdown HO8910 and HGSOC cells (31).…”

Dual inhibition of EGFR and IL-6-STAT3 signalling by miR-146b: a potential targeted therapy for epithelial ovarian cancer

“…It has been widely acknowledged that a number of pathways, including the epidermal growth factor receptor (EGFR) and STAT3 pathways, are aberrantly hyperactivated in human ovarian cancer 4,5 . Targeted inhibition of EGFR with a small molecule kinase inhibitor has significant clinical benefits in lung cancer with EGFR mutations 6 .…”

“…The IL-6-STAT3 pathway participates in a wide variety of tumour biological processes in ovarian and other solid cancers 5,8,9 . For instance, high levels of IL-6 promoted the progression of malignant ascites in ovarian cancer 10 .…”