LncRNA ANRIL Regulates Ovarian Cancer Progression and Tumor Stem Cell-Like Characteristics via miR-324-5p/Ran Axis.

Abstract

ObjectiveLong non-coding RNA (lncRNA) ANRIL is emerging as a crucial role in ovarian cancer progression and prognosis. However, the precise molecular mechanism of ANRIL on ovarian cancer is not known. Thus, we aim to study the underlying mechanism of ANRIL on the action.MethodsThe MTT assay assessed cell viability. Cell migration and invasion were determined using the wound healing assay, Transwell migration, and invasion assay. The relationships of ANRIL, miR-324-5p, and RAN were evaluated using luciferase activity assay and RNA pull-down assay. Cancer stem cell was identified by flow cytometry. Sphere formation assay was conducted to determine the stem-like properties. Xenograft tumor was established to assess tumor growth in vivo. qRT-PCR and Western blot were used to detect gene expression.ResultsANRIL was elevated while miR-324-5p was decreased in ovarian cancer tissues and cells. Besides, downregulated ANRIL enhanced miR-324-5p expression, and the luciferase reporting experiment and RNA pull-down assay showed the binding interaction between ANRIL and miR-324-5p. miR-324-5p directly targeted Ran and negatively modulated the expression of Ran. Besides, Ran was promoted by overexpressed ANRIL, which was reversed by overexpression of miR-324-5p. Furthermore, decreased ANRIL and increased miR-324-5p suppressed tumor growth, migration capacity, drug resistance, and alleviated stem-like characteristics in vitro and in vivo. Ran mediated the regulation of ANRIL on cell viability, stem-like properties, and drug resistance of ovarian cancer cells.ConclusionThe ANRIL/miR-324-5p/Ran axis regulated ovarian cancer development, making the axis meaningful targets for ovarian cancer therapy.