Long Noncoding RNA HOTAIR Contributes to Progression in Hepatocellular Carcinoma by Sponging miR-217-5p
Authors: Zhenya Zhu
Ximing Gong
Journal: Cancer Biotherapy and Radiopharmaceuticals (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: HCC; HOTAIR; apoptosis; invasion; miR-217-5p
Affiliations: Department of General Surgery, New Area People's Hospital of Pudong, Shanghai, China.

Abstract:  Background: Hepatocellular carcinoma (HCC) is an aggressive primary hepatic cancer with high malignancy and poor prognosis. Long noncoding RNA HOTAIR has been classified as an oncogene to accelerate cell proliferation, migration, and invasion in many cancer types by interacting with the miRNA. Therefore, we assumed that HOTAIR might participate in HCC cell progression by interacting with miR-217-5p expression. Materials and Methods: The expression of HOTAIR and miR-217-5p in 35 HCC patients and HCC cells was measured by quantitative real-time polymerase chain reaction. Cell transfection was conducted using Lipofectamine 2000 transfection reagent. CCK8 and flow cytometry was applied for the measurement of cell proliferation and apoptosis. Cell migration and invasion capacities were carried out by transwell assay. Xenograft mice were constructed by subcutaneously injecting of stably transfected Huh-7 cells in mice. The interaction between HOTAIR and miR-217-5p was determined by luciferase reporter system. Protein expression of P13K, p-P13K, AKT, p-AKT, MMP-2, and MMP-9 was analyzed using Western blot assay. Results: The expression of HOTAIR was upregulated, whereas miR-217-5p was downregulated in HCC tumor tissues and cell lines (Hep3B and Huh-7) compared with normal tissues and human normal liver cell line MIHA. In addition, HOTAIR expression was negatively correlated with miR-217-5p expression in HCC (r2 = 0.1867, p = 0.0171). More importantly, HOTAIR knockdown induced apoptosis and inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). In vivo experiments revealed that the interference of HOTAIR inhibited tumor growth. Subsequently, luciferase reporter system confirmed the interaction between HOTAIR and miR-217-5p. The rescue experiments clarified that miR-217-5p inhibitor attenuated the suppression of HOTAIR silencing on HCC cell proliferation, migration, invasion, and EMT. Furthermore, miR-217-5p inhibitor restored the inhibition of HOTAIR silencing mediated p-PI3K/p-AKT/MMP-2/9 protein expression. Conclusions: HOTAIR contributes to cell progression in HCC by sponging miR-217-5p, representing promising biomarkers for HCC treatment. 

Retracted: Yes

PubPeer comments:
 Fig 2C.  Cell apoptosis of Huh-7 and Hep3B cells at 48 h post-transfection evaluated by flow cytometric analysis ![file] Fig 5C.  The apoptotic rate of Huh-7 and Hep3B cells at 48 h post-transfection. ![file] These are curious flow-cytometry plots. Each shows local concentrations of cells in three of four quadrants, superimposed on a continuous background distribution of cells, showing an even distribution of PI and Annexin staining. Is this normal? , 
 Retracted [6 August 2021] . ----------------------------- *Cancer Biotherapy and Radiopharmaceuticals* officially retracts the paper entitled, u201cLong Noncoding RNA HOTAIR Contributes to Progression in Hepatocellular Carcinoma by Sponging miR-217-5p,u201d by Ximing Gong and Zhenya Zhu (Cancer Biother Radiopharm 2020;35(5):387u2013396; doi: 10.1089 cbr.2019.3070) due to the discovery that the paper was submitted from a paper mill, which is a violation of the journal s standard protocols and is considered an infraction against the rigorous standards of scientific publishing. The Editor and Publisher of *Cancer Biotherapy and Radiopharmaceuticals* are committed to preserving the scientific literature and the community it serves and does not tolerate any violations of scientific misconduct. ,