Mechanism of lncRNA PLACT1 in regulating the proliferation of pancreatic adenocarcinoma cells through the KLF2/KIAA1522 axis.

BACKGROUND

Pancreatic adenocarcinoma (PAAD) is among the most common cancers worldwide. This study aims to investigate the role of long noncoding RNA pancreatic cancer-associated transcript 1 (LncRNA PLACT1) in PAAD cell proliferation.

METHODS

PAAD and normal cells were cultured. The levels of PLACT1, Krüppel-like factor 2 (KLF2), and KIAA1522 were detected. After PLACT1 expression was interfered with, cell proliferation was detected using the cell counting kit-8, clone formation assay, and 5-ethynyl-2-deoxyuridine (EdU) staining. The binding of PLACT1 to euchromatic histone lysine methyltransferase 2 (EHMT2) was analyzed. The enrichment of EHMT2 and histone H3 lysine 9 dimethylation (H3K9me2) on the KLF2 promoter was analyzed by chromatin immunoprecipitation. KLF2 expression was detected after EHMT2 intervention. The binding of KLF2 to the KIAA1522 promoter was analyzed. The nude mouse xenograft model was constructed to detect the role of PLACT1 in vivo.

RESULTS

PLACT1 and KIAA1522 were highly expressed, and KLF2 was poorly expressed in PAAD cells. Silencing PLACT1 decreased cell proliferation, the number of cell clones, and EdU-positive cells. Mechanistically, PLACT1 inhibited KLF2 expression by recruiting EHMT2 to induce H3K9me2 in the KLF2 promoter region, resulting in reduced KLF2 enrichment at the KIAA1522 promoter and increased KIAA1522 expression. KLF2 downregulation or KIAA1522 overexpression alleviated the inhibitory effect of PLACT1 silencing on PAAD cell proliferation. PLACT1 silencing prevented PAAD tumorigenesis by regulating the KLF2/KIAA1522 pathway.

CONCLUSION

PLACT1 silencing inhibited PAAD by inhibiting KLF2 and promoting KIAA1522 expression, suggesting the therapeutic effect of PLACT1 silencing on PAAD.