Large Intervening Non-Coding RNA HOTAIR is Associated with Hepatocellular Carcinoma Progression

Abstract

Increasing evidence suggests that large intervening non-coding RNAs (lincRNAs) regulate key pathways in cancer invasion and metastasis. In this observational retrospective study, the expression of the oncogenic lincRNA HOX transcript antisense RNA (HOTAIR) gene was measured in 63 patients with hepatocellular carcinoma (HCC) following hepatic resection. The HOTAIR gene was significantly overexpressed in HCC tissues compared with adjacent non-tumour tissues. Patients with high HOTAIR gene expression in their tumours had an increased risk of recurrence after hepatectomy. There was also a significant correlation between HOTAIR expression and lymph node metastasis. In vitro assays in the HCC cell line Bel7402 demonstrated that knockdown of HOTAIR lincRNA reduced cell proliferation and was associated with reductions in levels of matrix metalloproteinase-9 and vascular endothelial growth factor protein, which are important for cell motility and metastasis. In conclusion, HOTAIR lincRNA might be a potential biomarker for the existence of lymph node metastasis in HCC.

Expression and prognostic impact of lncRNAs in acute myeloid leukemia

“…LncRNAs have emerged as important regulators of gene expression, showing cell-specific expression patterns and subcellular localization and are involved in many biological roles including imprinting, epigenetic regulation, apoptosis, and cell cycle (26,27). The well-characterized lncRNA HOX transcript antisense RNA (HOTAIR) has been found to be up-regulated in multiple cancers including breast, colorectal, hepatic, gastric, and pancreatic cancers (28)(29)(30)(31)(32)(33). HOTAIR modulates chromatin structures by serving as a scaffold and recruiting histone modifiers (28).…”

“…HOTAIR modulates chromatin structures by serving as a scaffold and recruiting histone modifiers (28). In breast cancer, HOTAIR promotes cancer cell invasion and metastasis in vivo through epigenetic silencing of metastasis suppressor genes (29)(30)(31)(32)(33). In patients with nonsmall cell lung cancer, high expression of the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was associated with metastases and poor survival, indicating its importance as a prognostic biomarker (34).…”

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

“…11,16 In fact, previous studies have shown that particular deregulated lncRNAs are important regulators of tumor formation and progression. 17,24 For example, the antisense intergenic RNA HOX Antisense Intergenic RNA (HOTAIR) is highly expressed in multiple types of primary somatic tumors, such as hepatocellular carcinoma, 25,26 pancreatic cancer, 27 and gastric cancer, 28 as well as some metastatic tumors, including metastatic breast tumors 29 and melanoma. 30 Moreover, high HOTAIR level is associated with poor patient survival rate 20,27 and tumor recurrence.…”

“…31 Moreover, HOTAIR can also interact with the LSD1/CoREST/REST complex, which coordinates targeting of LSD1 to chromatin for coupled histone K4 demethylation. 32 Given its important role in the epigenetic regulation of gene expression by mediating the modulation of chromatin structures, it is not surprising that HOTAIR performs vital functions in increasing cancer invasiveness and metastasis 25,26,29 and shows immense clinical relevance. Particularly, lncRNA expression levels may be extremely useful for monitoring tumors, and we consider lncRNAs to be novel cancer diagnostic tools and a source of future therapies.…”

The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine

“…Circulating nucleic acids (CNAs), both RNA and DNA species, are extracellular nucleic acids found in cell-free serum, plasma and other body fluids from healthy subjects, as well as from patients. 87 In addition, there is evidence of a good correlation between tumor-associated changes in genomic, epigenetic or transcriptional patterns, and alterations in CNA levels, 88 strongly pointing to the utility of this blood biomarker class as promising clinical tools. Our recent studies and others have suggested that cancer-specific miRNAs are stable and detectable in the blood, sputum and urine of cancer patients.…”