LncRNA ANRIL Regulates Ovarian Cancer Progression and Tumor Stem Cell-Like Characteristics via miR-324-5p/Ran Axis
Authors: Cong Ye
Ke Wang
Yu-Bo Hu
Ye Zhao
Journal: OncoTargets and Therapy (2021)
Discipline: CLINICAL MEDICINE
Keywords: ANRIL; cancer stem cell; drug resistance; migration; ovarian cancer
Affiliations: Department of Gynaecology and Obstetrics, The Third Hospital of Jilin University, Changchun, Jilin 130000, People's Republic of China., Department of Anesthesiology, The Third Hospital of Jilin University, Changchun, Jilin 130000, People's Republic of China., Department of Dermatology, The Third Hospital of Jilin University, Changchun, Jilin 130000, People's Republic of China.

Abstract:  Objective: 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. 

Retracted: Yes

PubPeer comments:
 This article is a falsification. Figure 4E: A micrograph has been duplicated and presented as something else. Figure 4F: The Western immunoblots do not have any background noise. Even if the contrast is enhaced to the most extreme, there is no background. Figure 5B: In two micrographs manipulation is seen. Figure 5C: Many of the Flow cytometry dot plots share areas with other dot plots that are too similar than you would expect. Figure 6D: Two micrographs have been manipulated. ![file] ![file] It is very disappointing and frustrating to still see this kind of obvious falsifications, after we have warned the publisher Dove Press for years. , 
 March 2021 retraction found here: https: www.dovepress.com retraction-lncrna-anril-regulates-ovarian-cancer-progression-and-tumo-peer-reviewed-article-OTT It reads:  The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. It was bought to the journalu2019s attention that several figures within the article appeared to have duplicated images (...). The authors were unable to provide a satisfactory explanation for the alleged duplication and were unable to provide the original images used in the figures. The editor determined the findings of the article were no longer valid and requested for the article to be rejected. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,