Oncotarget

Research Papers:

Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer

Yohei Sekino, Naoya Sakamoto, Keisuke Goto, Ririno Honma, Yoshinori Shigematsu, Kazuhiro Sentani, Naohide Oue, Jun Teishima, Akio Matsubara and Wataru Yasui _

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Oncotarget. 2017; 8:94259-94270. https://doi.org/10.18632/oncotarget.21688

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Abstract

Yohei Sekino1,2, Naoya Sakamoto1, Keisuke Goto3, Ririno Honma1, Yoshinori Shigematsu1,2, Kazuhiro Sentani1, Naohide Oue1, Jun Teishima2, Akio Matsubara2 and Wataru Yasui1

1Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan

2Department of Urology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan

3Cancer Biology Program, University of Hawaii Cancer Center, Honolulu, HI, USA

Correspondence to:

Wataru Yasui, email: wyasui@hiroshima-u.ac.jp

Keywords: Uc.63+, prostate cancer, miR-130b, droplet digital PCR, docetaxel

Received: June 03, 2017    Accepted: September 21, 2017    Published: October 09, 2017

ABSTRACT

Docetaxel is the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients ultimately become refractory due to the development of docetaxel resistance. The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis including prostate cancer (PC). In this study, we investigated the transcriptional levels of 26 representative T-UCRs and determined the regions that were differentially expressed in PC. Quantitative real-time polymerase chain reaction analysis revealed that the expression of T-UCR Uc.63+ was increased in PC tissues. MTT assay and wound healing assay revealed that Uc.63+ was involved in cell growth and cell migration. miR-130b was predicted to have binding sites within the Uc.63+ sequence. The expression of miR-130b was significantly disturbed by the overexpression or knockdown of Uc.63+. We also showed that Uc.63+ regulated the expression of MMP2 via miR-130b regulation. Furthermore, overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation. In patients treated with docetaxel, the expression of serum Uc.63+ in the docetaxel-resistant patients was higher than that in the docetaxel-sensitive patients (P = 0.011). Moreover, Kaplan-Meier analysis showed that the high expression of serum Uc.63+ correlated with a worse prognosis (P = 0.020). These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC.


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