miR‑27b‑3p and miR‑607 cooperatively regulate BLM gene expression by directly targeting the 3'‑UTR in PC3 cells

Chen,Yinglian; Zhao,Jiafu; Duan,Zhiqiang; Gong,Ting; Chen,Wei; Wang,Sainan; Xu,Houqiang

doi:10.3892/mmr.2019.10135

miR‑27b‑3p and miR‑607 cooperatively regulate BLM gene expression by directly targeting the 3'‑UTR in PC3 cells

Authors:
- Yinglian Chen
- Jiafu Zhao
- Zhiqiang Duan
- Ting Gong
- Wei Chen
- Sainan Wang
- Houqiang Xu
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Affiliations: Key Laboratory of Animal Genetics, Breeding and Reproduction in The Plateau Mountainous Region, Ministry of Education, Guizhou University, Guiyang, Guizhou 550025, P.R. China
Published online on: April 5, 2019 https://doi.org/10.3892/mmr.2019.10135
Pages: 4819-4831
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

BLM RecQ like helicase (BLM) has a pivotal role in genetic recombination, transcription, DNA replication and DNA repair, which presents the possibility of using BLM as an anti‑cancer target for treatment. However, the post‑transcriptional control regulation of BLM gene expression is not fully understood and limits the application of drugs targeting BLM for carcinoma therapy in the future. MicroRNAs (miRNAs) inhibit gene expression through interaction with the 3' untranslated region (3'‑UTR) of mRNA at the post‑transcriptional stage. Therefore, the current study screened for miRNAs that regulate BLM gene expression, with software predicting that miRNA (miR)‑27b‑3p, miR‑607, miR‑361‑3p, miR‑628‑5p and miR‑338‑3p. BLM gene expression levels in the PC3 prostate cancer cell line and RWPE‑2 normal prostate epithelium cell line were detected by reverse transcription‑quantitative PCR. Additionally, BLM mRNA levels were following miRNA overexpression for 24 and 48 h. For further miRNA filtration and validation, a dual‑luciferase reporter system and western blot analysis were performed, which demonstrated that miR‑27b‑3p and miR‑607 reduce BLM gene expression by directly targeting the BLM mRNA 3'‑UTR. A Box‑Behnken design experiment suggested that miR‑27b‑3p and miR‑607 have synergetic mutual effects on BLM gene expression. Finally, the suppressive effect of miR‑27b‑3p and miR‑607 on PC3 cell proliferation, colony formation, migration and invasion indicated the benefit of studying BLM as a drug target in cancer. In conclusion, the findings of the current provide evidence that miR‑27b‑3p and miR‑607 have an oncosuppressive function in PC3 cells and cooperatively downregulate BLM expression at the post‑transcriptional level.

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