INTRODUCTION: Accumulating evidence has indicated that long noncoding RNAs 
(lncRNAs) are pivotal regulators involved in the pathogenesis of cancer; 
however, the molecular mechanism of LINC00339 in colorectal cancer (CRC) remains 
unclear.
METHODS: The quantitative real-time polymerase chain reaction for the expression 
of LINC00339 and miR-378a-3p and Western blots for MED19 were performed. A 
dual-luciferase assay was used to investigate the interaction between LIN00339 
and miR-378a-3p, as well as between miR-378a-3p and MED19. Cell proliferation 
was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium 
bromide (MTT) and 5-ethynyl-2'-deoxyuridine (EdU) assay. The cell cycle was 
analyzed by propidium iodide staining followed by flow cytometry analysis. The 
wound-healing and transwell invasion assays were used to evaluate cell migration 
and invasion.
RESULTS: The expression of LINC00339 was significantly upregulated in CRC cells 
and tissues, and high LINC00339 expression indicated an advanced tumor stage. 
Further experiments demonstrated that SP1 activated LINC00339 expression by 
binding to its promoter region. Luciferase activity and RNA pull-down assays 
demonstrated a direct interaction between LINC00339 and miR-378a-3p. miR-378a-3p 
expression was decreased in CRC samples and negatively correlated with LINC00339 
expression in tumors. Gain- and loss-of-function assays indicated that LINC00339 
contributed to cell proliferation, cell cycle progression, migration, and 
invasion, while miR-378a-3p reversed these effects. Furthermore, cotransfection 
of wild-type MED19 3'-UTR reporters and miR-378a-3p significantly reduced 
luciferase activity. MED19 mRNA and protein expression was inhibited and 
enhanced by miR-378a-3p and LINC00339, respectively. MED19 overexpression 
reversed the effect of miR-378a-3p on cellular processes. Moreover, LINC00339 
promoted tumor growth in vivo and induced epithelial-mesenchymal transition 
(EMT) and activated the Wnt/β-catenin signaling pathway in cells.
CONCLUSION: Our findings demonstrate the regulatory role of the 
SP1/LINC00339/miR-378a-3p/MED19 axis in CRC tumorigenesis and provide novel 
insight into the molecular mechanism underlying CRC.