Downregulation of lncRNA PVT1 inhibits proliferation and migration of mesothelioma cells by targeting FOXM1

Oncology Reports 2022 February [Link]

Yutaro Fujii, Vishwa Jeet Amatya, Kei Kushitani, Rui Suzuki, Yuichiro Kai, Takahiro Kambara, Yukio Takeshima


Malignant mesothelioma is a highly aggressive tumor, and an effective strategy for its treatment is not yet available. Long non‑coding RNAs (lncRNAs) have been reported to be associated with various biological processes, including the regulation of gene expression of cancer‑related pathways. Among various lncRNAs, plasmacytoma variant translocation 1 (PVT1) acts as a tumor promoter in several human cancers, but its mechanism of action has not yet been elucidated. Increased PVT1 expression was identified in ACC‑MESO‑1, ACC‑MESO‑4, CRL‑5915, and CRL‑5946 mesothelioma cell lines. PVT1 expression was investigated in mesothelioma cell lines by reverse transcription‑quantitative polymerase chain reaction and its functional analysis by cell proliferation, cell cycle, cell migration, and cell invasion assays, as well as western blot analysis of downstream target genes. Knockdown of PVT1 expression in these cell lines by small interfering RNA transfection resulted in decreased cell proliferation and migration and increased the proportion of cells in the G2/M phase. The results of reverse transcription‑quantitative polymerase chain reaction analysis revealed that PVT1 knockdown in mesothelioma cell lines caused the downregulation of Forkhead box M1 (FOXM1) expression, while the results of western blot analysis revealed that this knockdown reduced FOXM1 expression at the protein level. In addition, combined knockdown of PVT1 and FOXM1 decreased the proliferation of mesothelioma cell lines. In conclusion, PVT1 and FOXM1 were involved in the proliferation of cancer cells. Therefore, PVT1‑FOXM1 pathways may be considered as candidate targets for the treatment of malignant mesothelioma.