OncoTargets and Therapy (Jan 2021)
LncRNA ANRIL Regulates Ovarian Cancer Progression and Tumor Stem Cell-Like Characteristics via miR-324-5p/Ran Axis
Abstract
Ke Wang,1 Yu-Bo Hu,2 Ye Zhao,3 Cong Ye1 1Department of Gynaecology and Obstetrics, The Third Hospital of Jilin University, Changchun, Jilin 130000, People’s Republic of China; 2Department of Anesthesiology, The Third Hospital of Jilin University, Changchun, Jilin 130000, People’s Republic of China; 3Department of Dermatology, The Third Hospital of Jilin University, Changchun, Jilin 130000, People’s Republic of ChinaCorrespondence: Cong YeDepartment of Gynaecology and Obstetrics, The Third Hospital of Jilin University, Changchun, Jilin 130000, People’s Republic of ChinaEmail [email protected]: Long 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.Methods: The 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.Results: ANRIL 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.Conclusion: The ANRIL/miR-324-5p/Ran axis regulated ovarian cancer development, making the axis meaningful targets for ovarian cancer therapy.Keywords: ANRIL, ovarian cancer, tumorigenicity, migration, drug resistance, cancer stem cell
