Long non-coding RNA UCA1 promotes the progression of paclitaxel resistance in ovarian cancer by regulating the miR-654-5p/SIK2 axis

Z.-Y. Li, X.-L. Wang, Y. Dang, X.-Z. Zhu, Y.-H. Zhang, B.-X. Cai, L. Zheng

Department of Gynecology, Gansu Provincial Maternity and Child-Care Hospital, Qilihe, Lanzhou, Gansu, China. uwgbpu@163.com

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• Oncology

OBJECTIVE: Ovarian cancer (OC) is a common tumor in women, and the development of chemoresistance is the major obstacle to its treatment. Long non-coding RNAs (LncRNAs) have been linked to chemoresistance in many cancers. However, the function of lncRNA urothelial carcinoma associated1 (UCA1) in paclitaxel (PTX) resistance of OC is not well elucidated.

PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of UCA1, microRNA-654-5p (miR-654-5p) and salt inducible kinase 2 (SIK2). Cell PTX resistance and proliferation were evaluated by 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The abilities of apoptosis, migration and invasion were measured by Flow cytometry and Transwell assays, respectively. Dual-luciferase reporter assay was used to verify the interaction among UCA1, miR-654-5p and SIK2. Besides, Western blot analysis was performed to assess the protein level of SIK2.

RESULTS: UCA1 was markedly upregulated in OC tissues and PTX-resistant OC cells. Silencing of UCA1 restrained the PTX resistance, reduced the proliferation, migration, invasion and enhanced the apoptosis of PTX-resistant OC cells. MiR-654-5p could be sponged by UCA1, and the inhibitory effect of its overexpression on the progression of PTX-resistant OC cells could be reversed by overexpressed-UCA1. Moreover, SIK2 was a target of miR-654-5p. Silencing of SIK2 could hinder the PTX resistance and suppress the progression of PTX-resistant OC cells, while miR-654-5p inhibitor could invert this inhibitory effect. Also, the expression of SIK2 was regulated by miR-654-5p and UCA1 expression.

CONCLUSIONS: LncRNA UCA1 plays an active role in PTX resistance of OC and is crucial to maintain the development of PTX resistance in OC, which provides a new therapeutic target for the study of OC chemoresistance.

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