Retracted: Long Noncoding RNA HOTAIR Contributes to Progression in Hepatocellular Carcinoma by Sponging miR-217-5p

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 (r 2 = 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.

Design and Functional Validation of a Mutant Variant of the LncRNA HOTAIR to Counteract Snail Function in Epithelial-to-Mesenchymal Transition

“…HOTAIR acts as a "mesenchymal" gene positively regulated in TGFb-induced EMT and is epistatic with respect to the EMT-TF Snail by controlling its repressive function in the chromatin context (13). Consistently, this lncRNA promotes tumorigenesis and metastasis formation in different epithelial cancers, including HCC: its increased expression causes the acquisition of metastatic properties while its knockdown impairs migration, invasion ability, and EMT in carcinoma cells (4,9,10,38,39). Coherently, HOTAIR repression is required in the maintenance of the epithelial differentiated state (11).…”

Roles of the HOX Proteins in Cancer Invasion and Metastasis

“…Recent findings have also related HOTAIR interference to Trastuzumab resistance in GC, through the sponging of miR-3030 and consequent upregulation of ERBB4 [133], which is responsible for activating the PI3K/ATK signalling pathway [134]. Several HOTAIR-dependent interferences in miR pathways have also been described in glioma [123], HCC [135][136][137] prostate cancer [138,139] and squamous cell carcinomas [140][141][142][143].…”

Roles of ncRNAs as ceRNAs in Gastric Cancer

“…It contains 2158 nucleotides, and its expression level in cancer tissues is higher than in normal tissues [ 8 ]. Studies have found that it functions as a ceRNA in the occurrence and development of GC, breast cancer [ 75 ], lung cancer [ 76 ], liver cancer [ 77 ], and other tumors [ 78 , 79 , 80 ], and it is also related to drug resistance [ 81 ].…”