Abstract
Evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in the regulation of tumor cellular processes, such as proliferation, apoptosis, and metastasis. LncRNA CRNDE (Colorectal Neoplasia Differentially Expressed) is located at human chromosome 16 and has been found overexpressed in a variety of cancers including colorectal cancer (CRC). In this paper, we report that lncRNA CRNDE expression was remarkably upregulated in CRC tissues and that lncRNA CRNDE overexpression was positively correlated with advanced pathological stages and larger tumor sizes. In addition, the knockdown of CRNDE significantly suppressed proliferation and caused apoptosis of CRC cells both in vitro and in vivo. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA CRNDE could epigenetically suppress the expressions of dual-specificity phosphatase 5 (DUSP5) and CDKN1A by binding to EZH2 (the key components of Polycomb repressive complex 2 (PRC2)), thus promoting CRC development. In conclusion, our data suggest that the lncRNA CRNDE promotes the progression of CRC and is a potential therapeutic target for CRC intervention.
Highlights
Considerable headway has been achieved in the diagnosis and therapy of colorectal cancer (CRC) in the past decade, it still causes significant morbidity and mortality, especially in the developed world.[1,2,3] According to the latest cancer statistics, CRC is the third most common cancer and third leading cause of cancer death worldwide.[2]
We first analyzed the expression level of the CRNDE in human CRC tissues by using microarray data downloaded from the Gene Expression Omnibus (GEO; GSE21510), and found that the CRNDE expression level was significantly upregulated in CRC tissues compared with that in normal tissues (Figure 1a)
We found that the expression levels of DUSP5 and CDKN1A were increased in si-EZH2-treated CRC cells (Po0.05) (Figure 6d), implying DUSP5 and CDKN1A may be the key downstream genes of CRNDE, and CRNDE can inhibit its expression by binding to EZH2
Summary
Considerable headway has been achieved in the diagnosis and therapy of colorectal cancer (CRC) in the past decade, it still causes significant morbidity and mortality, especially in the developed world.[1,2,3] According to the latest cancer statistics, CRC is the third most common cancer and third leading cause of cancer death worldwide.[2]. Expressed) is located at human chromosome 16 and has been found overexpressed in a variety of cancers including CRC.[20,21,22] A large number of studies have shown that CRNDE plays an important role in the occurrence and development of CRC, indicating a poor prognosis.[23] The upregulation of Received 23.2.17; revised 31.5.17; accepted 05.6.17; Edited by E Candi lncRNA CRNDE promotes the progression of CRC J Ding et al CRNDE expression has been shown to promote cell proliferation, migration, and invasion while inhibiting apoptosis of CRC.[24,25] the underlying molecular mechanisms involved in CRNDE interactions are complex and diverse. Our data suggest that the lncRNA CRNDE promotes the progression of CRC and is a potential therapeutic target for CRC intervention
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