Long non-coding RNA BLACAT1 inhibits prostate cancer cell proliferation through sponging miR-361

H.-Y. Li, F.-Q. Jiang, L. Chu, X. Wei

Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China. weinxin@jlu.edu.cn

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• Oncology

OBJECTIVE: LncRNAs play a key role in the development and progression of prostate cancer. In this study, the effects of the lncRNA BLACAT1 in prostate cancer were investigated.

PATIENTS AND METHODS: Real-time PCR was used to detect the expression of BLACAT1 and miR-361 in prostate cancer tissues and adjacent normal tissues (n=25). The function of BLACAT1 was detected through proliferation assay and apoptosis assay. The interaction between BLACAT1 and miR-361 in prostate cancer was studied by luciferase assay, RNA immunoprecipitation assay and chromatin immunoprecipitation analysis were performed to detect the BLACAT1 binding proteins. The xenograft mice experiment was performed to further confirm the functional significance of lncRNA BLACAT1 in vivo.

RESULTS: In patient samples and prostate cancer cell lines, BLACAT1 was down-regulated and inversely proportional to DNMT1, HDAC1, EZH2, MDM2 and miR-361 expression. Treatment with 5-azacytidine and chidamide enhanced BLACAT1 expression and decreased the levels of miR-361. The BALCAT1 promoter was methylated in prostate cancer tissue and found to interact with miR-361 via luciferase assays. BLACAT1 bound to EZH2, DNMT1 and HDAC1. ChIP-seq analysis revealed that HDAC1 interacts with STAT3, while EZH2 interacts with the mitogen-activated protein kinase (MAPK) promoter.

CONCLUSIONS: Two regulatory axes of BLACAT1-EZH2-MAPK and BLACAT1-HDAC1-STAT3 were identified to be associated with the progression of prostate cancer. Both chidamide and 5-azacytidine represent promising therapeutic options in prostate cancer treatment.

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