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Abstract
<p class="first" id="d2485109e140">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.
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