〔Abstract〕 Objective To investigate the effect of long non-coding RNA LUCAT1(lncRNA LUCAT1) on the biological behavior of MIA PaCa-2 in human pancreatic cancer cells, and to explore the potential role of LUCAT1 in the malignant progression of pancreatic cancer. Methods The mutation and expression of LUCAT1 in pancreatic cancer were analyzed by GEPIA, the expression levels of LUCAT1 in human pancreatic ductal cells HPNE and human pancreatic cancer cells were detected by q-PCR, and the expression and distribution of LUCAT1 in human pancreatic cancer tissues were detected by FISH. CCK-8 assay and Transwell assay were used to detect the effects of LUCAT1 on the proliferation, apoptosis, drug resistance, and migration of MIA PaCa-2 cells. Gene ensemble enrichment analysis was performed to compare the related signaling pathways involved in LUCAT1, and Western blot assay was used to verify the protein expression level. Results The results of GEPIA analysis showed that the expression level of LUCAT1 in human pancreatic cancer tissues was up-regulated, and the expression of LUCAT1 in human pancreatic cancer cells was significantly higher(P<0.05). Knockdown and overexpression of LUCAT1 could affect the proliferation, apoptosis, gemcitabine resistance, migration and invasion of pancreatic cancer cells, and the differences were statistically significant(P<0.05). In addition, LUCAT1 affected p-Akt expression levels in pancreatic cancer and was inhibited after treatment with Akt inhibitor MK-2206. Conclusion LUCAT1 regulates the malignant progression of MIA PaCa-2 in pancreatic cancer cells through the PI3K-Akt signaling pathway.