Micro-ribonucleic acid expression signature of metastatic castration-resistant prostate cancer: Regulation of NCAPH by antitumor miR-199a/b-3p

被引:19
作者
Arai, Takayuki [1 ,2 ]
Kojima, Satoko [3 ]
Yamada, Yasutaka [1 ,2 ]
Sugawara, Sho [1 ,2 ]
Kato, Mayuko [1 ,2 ]
Yamazaki, Kazuto [4 ]
Naya, Yukio [3 ]
Ichikawa, Tomohiko [2 ]
Seki, Naohiko [1 ]
机构
[1] Chiba Univ, Grad Sch Med, Dept Funct Genom, Chiba, Japan
[2] Chiba Univ, Grad Sch Med, Dept Urol, Chiba, Japan
[3] Teikyo Univ, Chiba Med Ctr, Dept Urol, Ichihara, Chiba, Japan
[4] Teikyo Univ, Chiba Med Ctr, Dept Pathol, Ichihara, Chiba, Japan
关键词
castration-resistant prostate cancer; micro-ribonucleic acid; miR-199a/b-3p; NCAPH; ribonucleic acid sequencing; CELL MIGRATION; CONDENSIN-II; TARGETS; INVASION; HEAD;
D O I
10.1111/iju.13911
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Objectives To identify oncogenes regulated by micro-ribonucleic acid, miR-199a/b-3p, in metastatic castration-resistant prostate cancer. Methods Advanced ribonucleic acid sequencing technologies were applied to construct a micro-ribonucleic acid expression signature using metastatic castration-resistant prostate cancer autopsy specimens. Ectopic expression of mature micro-ribonucleic acids or small-interfering ribonucleic acids were applied to functional assays for cancer cell lines. Genome-wide gene expression and in silico database analyses were carried out to predict micro-ribonucleic acid targets. Results Ectopic expression of miR-199a/b inhibited cancer cell aggressiveness. The gene coding for non-structural maintenance of chromosomes condensin I complex subunit H was directly regulated by miR-199a/b-3p. High expression of condensin I complex subunit H was significantly associated with poor disease-free survival by The Cancer Genome Atlas database analysis (P < 0.0001). Overexpression of condensin I complex subunit H was detected in hormone-sensitive prostate cancer and castration-resistant prostate cancer specimens, and knockdown assays showed that its expression enhanced cancer cell migration and invasive abilities. Conclusions Small ribonucleic acid sequencing of metastatic castration-resistant prostate cancer specimens showed the presence of several antitumor micro-ribonucleic acids whose targets are involved in hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer pathogenesis. Condensin I complex subunit H seems to be a promising diagnostic marker and therapeutic target for this disease. Our approach, based on the roles of anti-tumor micro-ribonucleic acids and their targets, will contribute to an improved understanding of the molecular pathogenesis of hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer.
引用
收藏
页码:506 / 520
页数:15
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