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.
Highlights
HOTAIR, a novel 158-bp Long noncoding RNAs (lncRNAs) resided in chromosome12q13.13 region, is involved in the progression of manyHepatocellular carcinoma (HCC) is an aggressive pri- diseases as essential regulators, such as diabetes and carmary hepatic cancer with high malignancy and poor diovascular diseases.[13,14] HOTAIR is frequently observed in Retracted prognosis.[1]
Increasing studies have identified that HOTAIR is closely implicated with various cancer progression; we aste sumed HOTAIR participates in the tumorigenesis of HCC
We transfected si-HOTAIR and siRNA negative control (si-NC) plasmids in Huh-7 and Hep3B cells to evaluate the regulatory effects of HOTAIR on HCC cell growth
Summary
Hepatocellular carcinoma (HCC) is an aggressive pri- diseases as essential regulators, such as diabetes and carmary hepatic cancer with high malignancy and poor diovascular diseases.[13,14] HOTAIR is frequently observed in Retracted prognosis.[1]. >200 nucleotides and involved in tumorigenesis, epithelialmesenchymal transition (EMT), and post-transcriptional processing.[8,9,10] HOX transcript antisense intergenic RNA (HOTAIR), derived from locus intergenic region, was reported to regulate epigenetic programming and facilitate tumorigenesis and metastasis by interacting with the histone demethylation enzyme lysine-specific demethylase 1.11,12 different cancer types and closely related to increased malignancy and poor prognosis due to the acceleration of tumor metastasis.[15] For example, HOTAIR elevated ZEB1 protein expression by sponging miR-217 to promote cell development in osteosarcoma.[16] What is more, HOTAIR knockdown led to reduction of cell viability and improvement of apoptosis by upregulating miR-148b in human lymphoma.[17].
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