Upregulation of the long non‐coding rna hotair promotes esophageal squamous cell carcinoma metastasis and poor prognosis

Abstract

Recent studies of the individual functionalities of long non-coding RNAs (lncRNAs) in the development and progression of cancer have suggested that HOX transcript antisense RNA (HOTAIR) is capable of reprogramming chromatin organization and promoting cancer cell metastasis. In order to ascertain the expression pattern of the lncRNA HOTAIR and assess its biological role in the development and progression of esophageal squamous cell carcinoma (ESCC), HOTAIR expression in ESCC tissues and adjacent noncancerous tissues were collected from 78 patients and measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). HOTAIR correlation with clinicopathological features and prognosis was also analyzed. Suppression of HOTAIR using siRNA treatment was performed in order to explore its role in tumor progression. Notably elevated HOTAIR expression levels were observed in cancerous tissues compared to adjacent noncancerous tissues (96%, P < 0.01), showing a high correlation with cancer metastasis (P < 0.01), elevated TNM (2009) stage classification (P < 0.01), and lowered overall survival rates (P = 0.003). Multivariate analysis revealed that HOTAIR expression (P = 0.003) is also an independent prognostic factor for comparison of TNM stage (P = 0.024) and lymph node metastasis (P = 0.010). Furthermore, in vitro assays of the ESCC cell line KYSE30 demonstrated that knockdown of HOTAIR reduced cell invasiveness and migration while increasing the response of cells to apoptosis. Thus, HOTAIR is a novel molecule involved in both ESCC progression and prognosis. Full elucidation of HOTAIR functionality relevant to ESCC may open avenues for the use of lncRNAs in identification of novel drug targets and therapies for ESCC and other prevalent cancers.

Upregulated long non-coding RNA SBF2-AS1 promotes proliferation in esophageal squamous cell carcinoma

“…Multiple types of lncRNA have been identified as associated with the development and progression of ESCC, including pist, colon cancer-associated transcript 2, homeobox transcript antisense RNA and metastasis-associated lung adenocarcinoma transcript 1 (26)(27)(28)(29)(30)(31). SBF2-AS1 is a novel lncRNA transcribed on chromosome 11p15.1 and, previously, its function and molecular mechanism in NSCLC has been reported (14).…”

HOTAIR: a cancer-related long non-coding RNA

“…HOTAIR reprogrammed the gene expression profile of ESCC cells, including genes involved in cell migration and cell cycle. [86]. Silencing the expression of HOTAIR in ESCC cells could suppress the tumor growth in both size and weight in a mouse xenograft model [87].…”

Long non-coding RNAs in cancer invasion and metastasis

“…20 Besides, HOTAIR expression levels were found to be correlated with metastasis in colorectal cancer and many other malignant neoplasms in liver, stomach, nasopharynx, esophagus, and skin, thus becoming a predictor of tumor recurrence in patients. 18,20,[70][71][72][73] In addition, the inhibition of MALAT1, which is associated with metastasis and poor prognosis, might be an effective therapeutic strategy for metastatic cancer. Importantly, the inhibition of MALAT1 does not affect normal cells because this protein is not required for the viability of these cells.…”