Background: Our study aims to investigate the effects of the knockout of long non-coding RNA LSINCT5 (lncRNA LSINCT5) on the proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and p38MAPK pathway of pancreatic cancer PANC-1 cells, to provide a basis for searching for the therapeutic targets of pancreatic cancer.
Methods: The laboratory findings and clinical data of 21 patients with pancreatic cancer were retrospectively collected, and the survival rates of patients with high or low lncRNA LSINCT5 expressions were analyzed. PANC-1 cells were randomly divided into the control group, shRNA-NC group, and sh-LSINCT5 group, and the constructed sh-LSINCT5 and shRNA-NC vectors were transfected into the corresponding cells. The successful interference of lncRNA LSINCT5 was confirmed by reverse transcription polymerase chain reaction (RT-PCR). CCK-8 and spherogenesis assay detected the proliferation and spherogenesis of PANC-1 cells. The apoptosis rate was evaluated by flow cytometry. Western blotting was used to identify the expressions of KI67, PCNA, SOX2, OCT4, E-cadherin, N-cadherin, and Vimentin and the activation of Caspase-3 and Caspase-9.
Results: The survival rate of patients with low lncRNA LSINCT5 expression was higher than that of patients with high lncRNA LSINCT5 expression. Compared with the control group, lncRNA LSINCT5 knockout significantly down-regulated the expressions of KI67, PCNA, SOX2, OCT4, cleaved Caspase-3, cleaved Caspase-9, N-cadherin and Vimentin (all P<0.05) and significantly decreased the cell proliferation, sphere size, and number of spheres in PANC-1 cells (all P<0.05); meanwhile, it up-regulated the protein expression of E-cadherin (P<0.05), along with the significantly increased number of apoptotic PANC-1 cells (P<0.05). In addition, compared with the control group, the level of p38 phosphorylation significantly dropped after lncRNA LSINCT5 knockout (P<0.05).
Conclusions: Knockout of lncRNA LSINCT5 can inhibit the proliferation, EMT, and p38MAPK pathway of PANC-1 cells and meanwhile promote the apoptosis of PANC-1 cells. Therefore, lncRNA LSINCT5 may be a promising therapeutic target for pancreatic cancer.
Keywords: apoptosis; epithelial-mesenchymal transition (EMT); lncRNA LSINCT5; pancreatic cancer; proliferation.
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