Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p.
Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p.
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DOI：
10.1038/s41598-021-90143-4
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发表时间：
2021-05-24
影响因子：
4.6
通讯作者：
Figg WD
中科院分区：
文献类型：
--
作者：
Barbier RH;McCrea EM;Lee KY;Strope JD;Risdon EN;Price DK;Chau CH;Figg WD
了解阿比特龙耐药性的机制仍然是优先事项，阿比特龙是批准用于治疗去势抵抗性前列腺癌的主要药物之一。有机阴离子多肽1B 3（OATP 1B 3，由SLCO 1B 3编码）转运蛋白已被证明可将雄激素转运到前列腺癌细胞中。本研究观察并探讨了阿比特龙诱导SLCO 1B 3表达的机制。用抗雄激素处理前列腺癌细胞（22 Rv 1、LNCaP和VCAP），并通过qPCR分析评估SLCO 1B 3表达。阿比特龙治疗增加了体外22 Rv 1细胞和体内22 Rv 1异种移植模型中SLCO 1B 3的表达。使用NanoString nCounter miRNA panel进行阿比特龙处理的22 Rv 1细胞的MicroRNA谱分析，随后进行miRNA靶标预测。TargetScan和米兰达预测工具鉴定hsa-miR-579- 3 p与SLCO 1B 3的3′非翻译区（3′UTR）结合。使用双荧光素酶报告基因检测，我们验证了hsa-miR-579- 3 p确实与SLCO 1B 3 3 3′UTR结合并显著抑制SLCO 1B 3报告基因活性。阿比特龙治疗显著下调hsa-miR-579- 3 p，表明其在上调SLCO 1B 3表达中的潜在作用。在这项研究中，我们证明了阿比特龙诱导SLCO 1B 3表达的一种新的miRNA介导的机制，SLCO 1B 3是一种转运蛋白，也是驱动雄激素剥夺治疗抵抗的原因。了解通过差异miRNA表达介导的阿比特龙耐药机制将有助于鉴定治疗耐药的潜在miRNA生物标志物和开发未来的治疗方法。
Understanding mechanisms of resistance to abiraterone, one of the primary drugs approved for the treatment of castration resistant prostate cancer, remains a priority. The organic anion polypeptide 1B3 (OATP1B3, encoded by SLCO1B3) transporter has been shown to transport androgens into prostate cancer cells. In this study we observed and investigated the mechanism of induction of SLCO1B3 by abiraterone. Prostate cancer cells (22Rv1, LNCaP, and VCAP) were treated with anti-androgens and assessed for SLCO1B3 expression by qPCR analysis. Abiraterone treatment increased SLCO1B3 expression in 22Rv1 cells in vitro and in the 22Rv1 xenograft model in vivo. MicroRNA profiling of abiraterone-treated 22Rv1 cells was performed using a NanoString nCounter miRNA panel followed by miRNA target prediction. TargetScan and miRanda prediction tools identified hsa-miR-579-3p as binding to the 3′-untranslated region (3′UTR) of the SLCO1B3. Using dual luciferase reporter assays, we verified that hsa-miR-579-3p indeed binds to the SLCO1B3 3′UTR and significantly inhibited SLCO1B3 reporter activity. Treatment with abiraterone significantly downregulated hsa-miR-579-3p, indicating its potential role in upregulating SLCO1B3 expression. In this study, we demonstrated a novel miRNA-mediated mechanism of abiraterone-induced SLCO1B3 expression, a transporter that is also responsible for driving androgen deprivation therapy resistance. Understanding mechanisms of abiraterone resistance mediated via differential miRNA expression will assist in the identification of potential miRNA biomarkers of treatment resistance and the development of future therapeutics.
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影响因子：
64.8
作者：
Li Z;Bishop AC;Alyamani M;Garcia JA;Dreicer R;Bunch D;Liu J;Upadhyay SK;Auchus RJ;Sharifi N
通讯作者：
Sharifi N
影响因子：
5.6
作者：
Benson EA;Eadon MT;Desta Z;Liu Y;Lin H;Burgess KS;Segar MW;Gaedigk A;Skaar TC
通讯作者：
Skaar TC
影响因子：
11.2
作者：
Li Y;Kuscu C;Banach A;Zhang Q;Pulkoski-Gross A;Kim D;Liu J;Roth E;Li E;Shroyer KR;Denoya PI;Zhu X;Chen L;Cao J
通讯作者：
Cao J
DOI：
10.1152/ajpgi.00297.2015
发表时间：
2016-06-01
影响因子：
4.5
作者：
Krattinger, Regina;Bostrom, Adrian;Kullak-Ublick, Gerd A.
通讯作者：
Kullak-Ublick, Gerd A.
影响因子：
7.3
作者：
Comuzzi, B;Nemes, C;Hobisch, A
通讯作者：
Hobisch, A