LncRNA HOTTIP PROMOTES OVARIAN CANCER CELL INVASION AND METASTASIS BY STABILIZING HIF-1α IN THE ANOXIC CELLULAR MICROENVIRONMENT

Background. The high recurrence rate and low survival rate of ovarian cancer (OC) patients are closely related to an anoxic environment. We aim to study the mechanism of long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) on hypoxia ovarian cancer cells (OCC) and its mechanism was investigated. Methods. Knockdown and overexpression of HOTTIP in human OCC (SKOV-3, OVCAR3) were performed. The expression levels of HOTTIP and HIF1a were monitored by qRT-PCR and WB. Transwell was conducted to validate the cell migration and invasion. ELISA was performed to calculate VEGF concentration in cells. Cell viability was monitored by CCK-8. Cell apoptosis and cycle were tested by flow cytometry. RNA pull-down was used to analyze the interaction between HIF-1a and HOTTIP. Results. HOTTIP was highly expressed in OCC. After HOTTIP knockdown, HIF-1 alpha expression and VEGF concentration in OCC were decreased. Cell migration, invasion, and cell viability were decreased. Cell apoptosis rate and G0/G1 phase cells were increased. RNA pull-down indicated a direct interaction between HIF-1 alpha and HOTTIP. Conclusions. HOTTIP formed a positive feedback loop with HIF-1 alpha to promote the development and metastasis of hypoxia ovarian cancer. This study provided theoretical support for the development of new OC treatment strategies.