Long non-coding RNA GAS6-AS1 acts as a ceRNA for microRNA-585, thereby increasingEIF5A2expression and facilitating hepatocellular carcinoma oncogenicity
Authors: Guanhui Zhou
Junhui Sun
Jing Ai
Tongyin Zhu
Li Jing
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: GAS6 antisense RNA 1; Hepatocellular carcinoma; eukaryotic translation initiation factor 5A2; microRNA-585.
Affiliations: Department of Ophthalmology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China., Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China.

Abstract:  Long non-coding RNA termed GAS6 antisense RNA 1 (GAS6-AS1) plays an essential role in gastric and non-small cell lung cancers. Nonetheless, the function of GAS6-AS1 in hepatocellular carcinoma (HCC) has not been so far studied in detail. In this study, reverse-transcription quantitative PCR was performed to measure GAS6-AS1 expression in HCC samples. A series of functional experiments, including MTT assay, colony formation assay, flow-cytometric analysis, and transwell migration and invasion assays, was performed to determine the influence of GAS6-AS1 knockdown on the malignant phenotype of HCC. The results showed that GAS6-AS1 was significantly upregulated in HCC tissue samples and cell lines. Increased GAS6-AS1 expression was associated with tumor size, Edmondson grade, and Tumor-Node-Metastasis (TNM) stage among patients with HCC. The overall survival of patients with HCC characterized with high expression of GAS6-AS1 was significantly shorter in comparison to that of patients with low level of GAS6-AS1. Functional experiments indicated that knockdown of GAS6-AS1 suppressed HCC cell proliferation, colony formation, migration, and invasion in vitro; promoted apoptosis in vitro; and decreased tumor growth in vivo. Of note, GAS6-AS1 was validated as a competing endogenous RNA (ceRNA) for microRNA-585 (miR-585) and consequently increased the expression of eukaryotic translation initiation factor 5A2 (EIF5A2). Finally, rescue experiments confirmed the association among GAS6-AS1, miR-585, and EIF5A2 in HCC cells. Our study provides substantial evidence that the GAS6-AS1/miR-585/EIF5A2 pathway plays an important role in HCC progression and that might be considered as a potential target for therapeutic approaches in HCC. 

Retracted: Yes

PubPeer comments:
 Could the authors comment on the duplication of a flow-cytometry plot from Figs 2d, 4d, 6c, 7d of this paper with one from Fig 2C of [Yin et al (2020)] ? ![file] Here in context: ![file] ![file] There may be other duplications, or matches with other panels from this oeuvre. https: docs.google.com spreadsheets d 1X401JM6CcpTSkbKsPsOl20pRKQ-ns1S_J5pTwtBjqPw edit#gid=0 , 
 The [Yin et al (2020)] paper was retracted [3 September 2021] , on account of coming from a papermill. , 
 The Transwell invasion migration assays overlap with papers by otherwise-unrelated teams of authors. *[left]* Fig 2e. *[right]* Fig 5e from  MicroRNA-761 targets FGFR1 to suppress the malignancy of osteosarcoma by deactivating PI3K Akt pathway ([Lv et al 2019] ) **[retracted]**. ![file] ----------------------------------------------------------- *[above]* **Fig 7e f**. *[lower left]* Fig 5d from  TRG-AS1 is a potent driver of oncogenicity of tongue squamous cell carcinoma through microRNA-543 Yes-associated protein 1 axis regulation ([He et al 2020] ) **[expression of concern]**. *[lower right]* Fig 7G from  Long Noncoding RNA FOXD2-AS1 Promotes the Malignancy of Cervical Cancer by Sponging MicroRNA-760 and Upregulating Hepatoma-Derived Growth Factor ([Hou et al 2020]()). ![] , 
 Retracted [21 June 2022] . --------------------------- We, the Editors and Publisher of the journal Cell Cycle, have retracted the following article: Jing Ai, Junhui Sun, Guanhui Zhou, Tongyin Zhu, and Li Jing. Long non-coding RNA GAS6-AS1 acts as a ceRNA for microRNA-585, thereby increasing EIF5A2 expression and facilitating hepatocellular carcinoma oncogenicity. Cell Cycle. 2020;19(7):742-757. doi: 10.1080 15384101.2020.1729323. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address all the concerns raised and have not been able to provide their original data in the required format. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. The authors do not agree with the retraction. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u2018Retractedu2019. ,