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

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.