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Research Paper|Volume 12, Issue 13|pp 12771—12782

HOTAIR expands the population of prostatic cancer stem-like cells and causes Docetaxel resistance via activating STAT3 signaling

Ning Wang1,2, Yaodong Jiang3, Shidong Lv3, Haoran Wen3, Dehua Wu1, Qiang Wei3, Qiang Dang3
  • 1Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China
  • 2Department of Oncology, Dongguan Kanghua Hospital, Dongguan 523000, Guangdong, China
  • 3Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China
* Equal contribution
Received: November 9, 2019Accepted: April 17, 2020Published: July 13, 2020
https://doi.org/10.18632/aging.103188

Copyright © 2020 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Prostatic cancer stem-like cells (PCSLCs) play an essential role in PCa development. Accumulating evidence suggests that androgen deprivation therapy (ADT) or chemotherapy using docetaxel could expand the population of PCSLCs. Therefore, understanding the underlying mechanisms responsible for PCSLCs expansion has broadly scientific interest. Here, our results revealed that lncRNA HOTAIR could increase PCSLCs population via activating STAT3 signaling. Mechanistically, HOTAIR functioned as miR-590-5p sponge and prevented it from targeting the 3’UTR of IL-10, one upstream molecule of STAT3 signaling, leading to IL-10 upregulation and STAT3 activation. We also found that HOTAIR was required and sufficient to cause Docetaxel resistance (DocR) in C4-2 PCa cells. Moreover, our in vivo animal study also confirmed that Du145-HOTAIR mice had a faster tumor growth rate and a poorer survival rate compared to control cohorts. Our data build compelling rationale to target HOTAIR for the depletion of PCSLCs and alleviation of Docetaxel resistance.