Abstract
Hepatocellular carcinoma (HCC) is the most common subtype of liver malignancy, and it is characterized by poor prognosis because of cancer stem cell (CSC)-mediated high postsurgical recurrence rates. Thus, targeting CSCs, or HCC cells with CSC-like properties, is an effective strategy for HCC therapy. Here, using long noncoding RNA (lncRNA) microarray analysis, we identified a novel lncRNA termed lncCAMTA1 that is increased in both liver CSCs and HCC. High lncCAMTA1 expression in HCC indicates poor clinical outcome. In vitro and in vivo functional experiments showed that overexpression of lncCAMTA1 promotes HCC cell proliferation, CSC-like properties, and tumorigenesis. Conversely, depletion of lncCAMTA1 inhibits HCC cell proliferation, CSC-like properties, and tumorigenesis. Mechanistically, we demonstrated that lncCAMTA1 physically associates with the calmodulin binding transcription activator 1 (CAMTA1) promoter, induces a repressive chromatin structure, and inhibits CAMTA1 transcription. Furthermore, CAMTA1 is required for the effects of lncCAMTA1 on HCC cell proliferation and CSC-like properties, and the expression of lncCAMTA1 and CAMTA1 is significantly negatively correlated in HCC tissues. Collectively, our study revealed the important roles and underlying molecular mechanisms of lncCAMTA1 on HCC, and suggested that lncCAMTA1 could be an effective prognostic factor and a potential therapeutic target for HCC.
Highlights
Liver cancer is the fifth most common cancer and the second highest cause of cancer-related death in men worldwide [1]
In this study, combining Liver cancer stem cells (LCSCs) microarray results [34] with two human Hepatocellular carcinoma (HCC) microarray results (GSE58043 and GSE55191), we identified an intriguing long noncoding RNA (lncRNA), termed lncCAMTA1, whose expression is upregulated in both LCSCs and HCC
Many lncRNAs differentially expressed in LCSCs were identified by microarray in a previous report [34]
Summary
Liver cancer is the fifth most common cancer and the second highest cause of cancer-related death in men worldwide [1]. The high postsurgical recurrence rates are mainly ascribed to the heterogeneous population of HCC cells including a subset of cancer stem cells (CSCs), which have the capacity to self-renew, differentiate, and give rise to a new cancer [9,10,11]. They are considered to account for the initiation, progression, metastasis and relapse of cancers [12]. Using in vitro and in vivo functional experiments, we investigated the roles and underlying molecular mechanisms of lncCAMTA1 on proliferation, CSC-like properties, and tumorigenesis of HCC cells
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