Overexpression of CASC19 indicates poor prognosis and facilitates proliferation, migration and invasion in colorectal cancer

Jiang Zhao, Cong Li, Shiqing Chen, Ye Xu, Fangqi Liu


Background: Recent studies reveal lncRNAs are associated with tumor progression or metastasis in colorectal cancer (CRC). However, the functional roles of lncRNAs in colorectal liver metastases (CRLM) are still poorly understood. In this study, we performed an integrative analysis of long noncoding RNAs (lncRNAs) of CRLM in Chinese population.
Methods: We first applied RNA-seq and Short Time-series Expression Miner (STEM) to identify differentially expressed lncRNAs in normal tissues, tumor tissues and matched liver metastasis tissues in discovery cohort including four patients with CRLM, and subsequently differentially expressed lncRNAs were checked in the validation cohort consisting of 21 patients with CRLM by qRT-PCR. Then we analyzed the association between lncRNAs and overall survival (OS) in the third cohort with 108 CRC patients. Finally, we investigated the function of lncRNAs in HCT-116 and LoVo cell lines.
Results: RNA-seq and STEM analysis identified four lncRNAs (HL-5, HL-20, HL-38, and HL-59) according with the expression trend of N (normal tissues) < T (tumor tissues) < M (matched liver metastasis tissue), which may be associated with CRLM. Univariate analyses showed that high CASC19 expression was associated with poorer prognosis (P=0.013). CASC19 knockdown inhibited cell migration more than 50% in LoVo cells and HCT-116 cells (P<0.001), and significantly decreased cell invasion (P<0.001), as determined with the Matrigel assays. In contrast, cell invasion and migration were increased when CASC19 was overexpressed in HCT-116 and LoVo cells (P<0.001).
Conclusions: Our results showed that liver metastasis tissues and primary tissues of CRC had different expression profiles of lncRNAs. We suggest that CASC19 is a promising biomarker for CRC patients.