N<sup>6</sup>‑methyladenosine‑induced long non‑coding RNA PVT1 regulates the miR‑27b‑3p/BLM axis to promote prostate cancer progression

Chen,Bin; Chen,Bin; Liu,Chang; Liu,Chang; Long,Hong; Long,Hong; Bai,Guohui; Bai,Guohui; Zhu,Yuhang; Zhu,Yuhang; Xu,Houqiang; Xu,Houqiang

doi:10.3892/ijo.2022.5464

N⁶‑methyladenosine‑induced long non‑coding RNA PVT1 regulates the miR‑27b‑3p/BLM axis to promote prostate cancer progression

Authors:
- Bin Chen
- Chang Liu
- Hong Long
- Guohui Bai
- Yuhang Zhu
- Houqiang Xu
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Affiliations: Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region (Ministry of Education), College of Life Sciences, Guizhou University, Guiyang, Guizhou 550025, P.R. China, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, P.R. China, School of Stomatology, Zunyi Medical University, Zunyi, Guizhou 563006, P.R. China, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563006, P.R. China
Published online on: December 7, 2022 https://doi.org/10.3892/ijo.2022.5464
Article Number: 16
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Prostate cancer (PCa) is one of the most fundamental causes of cancer‑related mortality and morbidity among males. However, the underlying mechanisms have not yet been fully clarified. The present study aimed to investigate the effects of plasmacytoma variant translocation 1 (PVT1) on the malignant behaviors of PCa cells and to explore the possible molecular mechanisms involved. The expression levels of PVT1 and microRNA (miRNA/miR)‑27b‑3p in PCa tissues and cell lines were measured using reverse‑transcritpion‑quantitative polymerase chain reaction. Methyltransferase 3 (METTL3)‑mediated PVT1 N⁶‑methyladenosine (m⁶A) modifications were detected using RNA immunoprecipitation (RIP) and RNA pull‑down assays. Bioinformatics analysis was used to predict the interactions of miR‑27b‑3p with PVT1 and bloom syndrome protein (BLM), and these interactions were validated using RIP, dual‑luciferase reporter and biotin pull‑down assays. The functional importance of miR‑27b‑3p, PVT1 and BLM within PCa cells was assessed through the in vitro utilization of Cell Counting Kit‑8, Transwell, wound healing and colony formation assays, and the in vivo use of a mouse xenograft model. The results revealed the high expression level of PVT1 in PCa tissues and cells, and epigenetic analyses revealed the upregulation of PVT1 expression following METTL3‑mediated m⁶A modification. PVT1 overexpression induced PCa cells to become more proliferative, migratory and invasive, whereas PVT1 knockdown led to the opposite phenotype. Furthermore, miR‑27b‑3p was found to target both PVT1 and BLM, and PVT1 functioned to sequester miR‑27b‑3p within cells, thereby indirectly promoting the BLM expression level. BLM overexpression reversed the adverse effects of PVT1 knockdown on the migratory, proliferative and invasive capabilities of PCa cells in vitro and in vivo. The overexpression of PVT1 contributed to the aggressive phenotype of PCa cells by regulating the miR‑27b‑3p/BLM axis. On the whole, the findings of the present study may provide novel potential targets for the treatment of PCa.

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