Details

Autor(en) / Beteiligte

• Jiang, Xingkang
• Guo, Shanqi
• Zhang, Yangyi
• Zhao, Yang
• Li, Xiaojiang
• Jia, Yingjie
• Xu, Yong
• Ma, Baojie

Titel

LncRNA NEAT1 promotes docetaxel resistance in prostate cancer by regulating ACSL4 via sponging miR-34a-5p and miR-204-5p

Ist Teil von

• Cellular signalling, 2020-01, Vol.65, p.109422, Article 109422

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• •NEAT1 was upregulated in docetaxel-resistant PCa clinical samples and cell lines.•NEAT1 enhanced docetaxel resistance in PCa cells in vitro and in vivo.•NEAT1 targeted miR-34a-5p and miR-204-5p and repressed its expression.•miR-34a-5p and miR-204-5p suppressed ACSL4 to reduce docetaxel resistance of PCa.•ACSL4 promoted docetaxel resistance in PCa by NEAT1, miR-34a-5p and miR-204-5p axis. Docetaxel resistance remains one of the main problems in clinical treatment of metastatic prostate cancer (PCa). Previous studies identified differently expressed lncRNAs in docetaxel-resistant PCa cell lines, while the potential mechanisms were still unknown. In the present study, we found NEAT1 was expressed at high levels in docetaxel-resistant PCa clinical samples and related cell lines. When knockdown NEAT1, cell proliferation and invasion in docetaxel-resistant PCa cells in vitro and in vivo were downregulated. Our further researches explained that NEAT1 exerts oncogenic function in PCa by competitively ‘sponging’ both miR-34a-5p and miR-204-5p. Inhibition of miR-34a-5p or miR-204-5p expression mimics the docetaxel-resistant activity of NEAT1, whereas ectopic expression of miR-34a-5p or miR-204-5p attenuates the anti-drug function of NEAT1 in PCa cells. Besides, we also found ACSL4 is a target of both miR-34a-5p and miR-204-5p, and ACSL4 was also inhibited by miR-34a-5p and miR-204-5p. Moreover, suppression of miR-34a-5p or/and miR-204-5p greatly restrained the expression of ACSL4 upon NEAT1 overexpression. Joint expression of miR-34a-5p and miR-204a-5p synergistically decreased the expression of ASCL4, indicating miR-34a-5p and miR-204a-5p collaboratively inhibit the expression of ACSL4. Innovatively, we concluded that NEAT1 contributes to the docetaxel resistance by increasing ACSL4 via sponging miR-34a-5p and miR-204-5p in PCa cells.