Background: Long-noncoding RNAs (lncRNAs) could exert a crucial effect on the development of human cancers, including CRC. However, the biological function and underlying mechanism of LINCRNA00460  in the development of CRC still need deeper exploration.
Materials and Methods: The expression of LINC00460  in CRC tissues and cell lines was assessed by qRT-PCR. Cell proliferation, migration, and invasion were measured by the respective cell counting Kit-8 (CCK-8), wound healing assay and transwell invasion assay. Cell apoptosis and caspase-3 activity were detected by flow cytometry and caspase-3 activity assay. The relationship between LINC00460 and miR-613 expression was explored by Dual-luciferase reporter assay. Protein expression was measured by Western blotting. In vivo tumour growth was evaluated using a xenograft model of nude mice.
Results: LINC00460 was markedly up-regulated in CRC tissues and cell lines compared to their corresponding controls, which was closely correlated with clinical stage, TNM (T) classification, nodal (N) classification, metastasis (M) classification, liver metastasis and pathological differentiation, and survival rate of CRC patients. Functionally, LINC00460  knockdown decreased the proliferative, migrative and invasive abilities, and enhanced apoptosis rates and caspase-3 activity in HT29 and LOVO cells. Mechanistic studies indicated that miR-613  was targeted by LINC00460 , and SphK1  was targeted and inversely regulated by miR-613 in HT29 and LOVO cells. In vivo studies, LINC00460 knockdown attenuated tumour growth. MiR-613 downregulation and SphK1 upregulation in the CRC tissues, and LINC00460 expression levels were inversely correlated with miR-613 expression and positively correlated with the SphK1 mRNA expression. Overall, LINC00460 modulated cell proliferation, migration, invasion and sphingosine kinase 1 (SphK1) expression in HT29 and LOVO cells, at least in most part, by regulating miR‐613.
Conclusion: LINC00460 functions as a competing endogenous RNA to regulate SphK1 expression by sponging miR‐613 in CRC and provides a valuable therapeutic strategy for CRC patients.
Keywords: long noncoding RNA 00460, miR‐613, colorectal cancer, SphK1