The International Journal of Romanian Society of Endocrinology / Registered in 1938

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July - September 2022, Volume 18, Issue 3

Zhang S, Ma Q, Wu X, Chen P

LncRNA HOTTIP Promotes Ovarian Cancer Cell Invasion And Metastasis By Stabilizing Hif-1a In The Anoxic Cellular Microenvironment

Acta Endo (Buc) 2022, 18 (3): 263-270
doi: 10.4183/aeb.2022.263

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 HIF- 1α 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-1α and HOTTIP. Results. HOTTIP was highly expressed in OCC. After HOTTIP knockdown, HIF-1α 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-1α and HOTTIP. Conclusions. HOTTIP formed a positive feedback loop with HIF-1α to promote the development and metastasis of hypoxia ovarian cancer. This study provided theoretical support for the development of new OC treatment strategies.

Keywords: LncRNA HOTTIP, HIF-1a, ovarian cancer, anoxic microenvironment.

Correspondence: Puxiang Chen MD, The Second Xiangya Hospital of Central South University, Hunan, 410000, China, E-mail: