Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence

Abstract

Abstract. The present study aimed to investigate the expression level of HOX transcript antisense RNA (HOTAIR) in hepatocellular carcinoma (HCC) and its association with various clinicopathological characteristics, and to further explore the molecular mechanisms of HOTAIR function in HCC. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of HOTAIR in 60 paired fresh HCC samples and adjacent normal liver tissue samples. The association between HOTAIR expression and clinicopathological parameters was analyzed. Lentivirus-mediated HOTAIR-specific small hairpin RNA vectors were transfected into HepG2 cells. Cell proliferation and invasion in vitro were examined by MTT and Transwell assays, respectively. A xenograft model was used to analyze the tumorigenesis of liver cancer cells in vivo. In addition, semi-quantitative RT-PCR was used to detect the expression level of Wnt/β-catenin signaling molecules under the condition of HOTAIR inhibition. The results revealed that the expression level of HOTAIR in HCC tissues was higher than that in adjacent non-cancerous tissues. HOTAIR expression was significantly associated with poor tumor differentiation (P=0.002), metastasis (P=0.002) and early recurrence (P=0.001). In vitro, the inhibition of HOTAIR in liver cancer cells resulted in the suppression of cell proliferation and invasion. HOTAIR depletion significantly inhibited the rate of growth of liver cancer cells in vivo. Furthermore, the expression levels of Wnt and β-catenin were downregulated when HOTAIR expression was suppressed. In conclusion, HOTAIR is important in the progression and recurrence of HCC, partly through the regulation of the Wnt/β-catenin signaling pathway. Targeting HOTAIR may be a novel therapeutic strategy for HCC.

Knockdown of long non‑coding RNA HOTAIR sensitizes hepatocellular carcinoma cell to cisplatin by suppressing the STAT3/ABCB1 signaling pathway

“…In addition, HOTAIR was demonstrated to promote proliferation and reduce apoptosis in pancreatic cancer, colorectal cancer, and HCC (10)(11)(12). Overexpression of HOTAIR was positively associated with poor prognosis, tumor progression and recurrence in HCC (13,14). A recent study reported that HOTAIR also promoted the malignant growth of human liver cancer stem cells (15).…”

“…A recent study reported that HOTAIR also promoted the malignant growth of human liver cancer stem cells (15). A number of studies implicated that HOTAIR has important roles in the tumorigenesis of HCC (12)(13)(14)(15) Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RT-qPCR was performed to determine expression of lncRNA HOTAIR (12), and mRNA expression of ABCB1 (16).…”

HOTAIR, a long non-coding RNA driver of malignancy whose expression is activated by FOXC1, negatively regulates miRNA-1 in hepatocellular carcinoma

“…It has been reported that lncRNA HOX transcript antisense intergenic RNA (HOTAIR) expression is significantly higher in HCC tissues than in adjacent non-cancerous tissues (7). Patients with HCC tumors that overexpress HOTAIR have an increased risk of HCC recurrence following hepatectomy, and there is also a correlation between HOTAIR overexpression and increased risk of lymph node metastasis (8). The overexpression of HOTAIR is an independent prognostic factor for HCC recurrence in liver transplant patients (9).…”

Long non‐coding PANDAR as a novel biomarker in human cancer: A systematic review

“…[11][12][13] HOTAIR causes the transcriptional suppressing of the HOXD locus on chromosome 2 in trans. 14 It recruits polycomb repressiving complex 2 (PRC2) and regulates the chromosome occupancy of EZH2 (a subunit of PRC2), which causes histone H3 lysine 27 trimethylation of the HOXD locus.…”