LncRNA PVT1 in bone marrow mesenchymal stem cells suppresses prostate cancer progression via targeting miR-122 in tumor microenvironment

Abstract: Background: Prostate cancer progression is influenced by the tumor microenvironment. Bone marrow mesenchymal stem cells (BMSCs) can modulate tumor behavior, but the role of their lncRNA PVT1 is unclear. Objective: To investigate whether lncRNA PVT1 in BMSCs regulates the malignant phenotype of prostate cancer cells through miR-122 and elucidate its mechanism of action in the tumor microenvironment. Method: Rat BMSCs were isolated and cultured and a Transwell co-culture system was established with human prostate cancer cell lines (PC-3). RT-qPCR was used to detect the expression of PVT1 and miR-122 in BMSCs and cancer cells. PVT1 was overexpressed and knocked down in BMSCs to observe its effects on cancer cell proliferation (CCK-8), apoptosis (flow cytometry) and cell cycle (PI staining) in the co-culture system. The targeting relationship between PVT1 and miR-122 was validated using a dual-luciferase reporter assay. Rescue experiments were performed by simultaneously manipulating PVT1 and miR-122 in BMSCs. Results: In prostate cancer patient tissues and cell lines, PVT1 expression was downregulated while miR-122 expression was upregulated. In the co-culture system, overexpression of PVT1 in BMSCs significantly inhibited cancer cell proliferation, arrested the cell cycle at the G0/G1 phase and promoted apoptosis. Conversely, knockdown of PVT1 in BMSCs promoted the malignant phenotype of cancer cells. Mechanistically, PVT1 directly targeted and negatively regulated miR-122. Overexpression of miR-122 reversed the inhibitory effect of PVT1 overexpression in BMSCs on cancer cells. Conclusion: BMSCs exert a tumor-suppressive effect in the prostate cancer microenvironment through the PVT1/miR-122 axis, which may serve as a novel therapeutic target for prostate cancer.