Increasing evidence suggests that long non-coding RNAs (lncRNAs) are aberrantly expressed in colorectal cancer (CRC); however, only few CRC-related lncRNAs have been characterized. In this study, we aimed to dig out potential dysregulated lncRNAs that are highly involved in CRC development. Using a lncRNA-mining approach, we performed lncRNA expression profiling in a large CRC cohort from Gene Expression Ominus (GEO), GSE39582 test series (N = 585). We identified 31 downregulated lncRNAs and 16 upregulated lncRNAs from the GSE39582 test series patients (566 tumor patients and 19 normal controls). The reliability of lncRNA expression profiles was further confirmed by RT-qPCR in carcinoma tissues and paired adjacent normal tissues from 30 CRC patients, also in the serum from 109 CRC patients, and 99 normal individuals. We demonstrated that the expression of SLC25A25-AS1, which has not been reported previously, was significantly decreased in both the tumor tissues (27 out of 30) and serum of CRC patients. SLC25A25-AS1 overexpression significantly inhibited proliferation and colony formation in colorectal cancer cell lines, and downregulation of SLC25A25-AS1 obviously enhanced chemoresistance and promoted EMT process in vitro associated with Erk and p38 signaling pathway activation. Therefore, SLC25A25-AS1 was determined to play a tumor suppressive role in CRC. Our results might provide a lncRNA-based target for CRC treatment.
Keywords: Chemoresistance; Colorectal cancer; EMT; Long non-coding RNA; SLC25A25-AS1.