High expression of long non‑coding HOTAIR correlated with hepatocarcinogenesis and metastasis

Abstract

HOX transcript antisense RNA (HOTAIR), a newly discovered long noncoding RNA (lncRNA), has been reported to be a poor prognostic marker in many types of cancers. The current study attempted to investigate the biological roles and clinicopathlogical implications of HOTAIR in hepatocellular carcinoma (HCC), as well as understand the molecular mechanisms of HOTAIR in HCC progression. HOTAIR expression in 95 HCC patients with paired HCC tissues and adjacent non‑cancer tissues were investigated using quantitative reverse transcription‑polymerase chain reaction. The association between HOTAIR expression and clinicopathological features was assessed. The effects of HOTAIR were examined in vitro assays by silencing the lncRNA. Pathway analyses were performed to illustrate the biological functions of the HOTAIR and coexpression genes. The expression level of HOTAIR was observed significantly higher in the HCC tissue than the adjacent non‑tumor tissue. HOTAIR expression levels were significantly higher in tumor samples from patients with distant metastasis, advanced stage, portal vein tumor embolus, vasoinvasion, tumor capsular infiltration or positive nm23 expression than those from patients without these conditions, correspondingly. The silencing of HOTAIR in liver cancer cells induced the inhibition of cell proliferation and promotion of apoptosis. Several pathways such as extracellular matrix‑receptor interaction, focal adhesion, pathways in cancer were annotated with the HOTAIR and coexpression genes. In summary, the present analysis indicates that HOTAIR might be an oncogene in HCC. It functions though promoting tumor cell growth and inhibiting apoptosis. HOTAIR may potentially be involved in HCC metastatic progression by several pathways correlated to cell adhesion, and may be a therapeutic target in future.

The Role of Long Non-Coding RNAs in Hepatocarcinogenesis

“…Several studies showed that HOTAIR levels are elevated in HCC [ 82 , 83 , 84 , 85 , 86 , 87 ], and that its expression is associated with patients with increased risk of recurrence or metastasis [ 82 , 86 ], poor prognosis [ 84 ] and significantly shorter recurrence-free survival [ 83 ]. At the cellular level, HOTAIR is involved in proliferation, cell motility, viability and invasion, cell cycle progression, apoptosis, autophagy, and chemotherapeutic sensitivity of cancer cells to cisplatin and doxorubicin [ 83 , 84 , 85 , 86 , 87 , 88 , 117 , 118 , 119 , 120 ].…”

A Systematic Review of Long Noncoding RNAs in Hepatocellular Carcinoma: Molecular Mechanism and Clinical Implications

“…“HOX transcript antisense intergenic RNA” or HOTAIR is a lncRNA (2.2 kb length) which originates from the HOXC antisense strand [ 23 ]. HOTAIR is overexpressed in HCC cells and tissues [ 24 – 27 ] and is associated with worse prognosis, shorter recurrence-free survival, and increased risk of recurrence after hepatic transplantation [ 26 , 28 , 29 ]. Functionally, HOTAIR enhances proliferation, migration, glycolysis, autophagy, and chemoresistance in HCC cells ( Table 1 ).…”

Diagnostic roles of HOX transcript antisense intergenic RNA in cancer

“…[37][38][39] In this study, 17 articles with 20 studies were examined to study the role of HOTAIR in the diagnosis of different types of cancer, including GC, GBM, ESCC, NSCLC, Many studies also provided evidence that HOTAIR could be a promising diagnostic biomarker for cancer. 20,22,40,41 A study showed that the expression of plasma HOTAIR increased significantly in patients with BC. 40 Higher levels of plasma HOTAIR were found in patients with GC with 88% sensitivity and 84% specificity; additionally, an increased levels of HOTAIR was associated with advanced tumor stages and metastasis.…”