Long noncoding RNA (lncRNA) highly upregulated in liver cancer (HULC) has been reported to be implicated in chemoresistance. However, the potential mechanism of HULC in paclitaxel (PTX)-resistant ovarian cancer (OC) remains undefined. The expression of RNAs and proteins was measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot assay. The PTX resistance and apoptotic rate were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Furthermore, the interaction between miR-137 and HULC or integrin beta-8 (ITGB8) was predicted by miRcode and starBase v2.0 and then verified by dual luciferase reporter and RNA pull-down assays. In addition, the xenograft mice model was established to explore the effects of HULC in vivo . HULC was significantly upregulated and miR-137 was downregulated in PTX-resistant OC tissues and cells. Also, the HULC depletion suppressed tumor growth and PTX resistance in PTX-treated mice. miR-137 was verified as a target of HULC and directly targeted ITGB8. And HULC knockdown downregulated ITGB8 expression by targeting miR-137. miR-137 inhibitor or ITGB8 overexpression mitigated the suppressive impacts of HULC knockdown on PTX resistance. Collectively, HULC modulated ITGB8 expression to promote PTX resistance of OC by sponging miR-137.

中文翻译：

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长链非编码 RNA HULC 通过 miR-137/ITGB8 轴促进卵巢癌的紫杉醇耐药

据报道，在肝癌 (HULC) 中高度上调的长链非编码 RNA (lncRNA) 与化学抗性有关。然而，HULC 在紫杉醇 (PTX) 耐药卵巢癌 (OC) 中的潜在机制仍未明确。RNA 和蛋白质的表达通过定量逆转录酶聚合酶链反应 (qRT-PCR) 和蛋白质印迹法测定。分别通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 测定和流式细胞术评估 PTX 抗性和凋亡率。此外，miR-137 和 HULC 或整合素 beta-8 (ITGB8) 之间的相互作用由 miRcode 和 starBase v2.0 预测，然后通过双荧光素酶报告基因和 RNA 下拉分析进行验证。此外，还建立了异种移植小鼠模型，以探讨 HULC 在体内的作用。在 PTX 抗性 OC 组织和细胞中，HULC 显着上调，miR-137 下调。此外，HULC 耗竭抑制了 PTX 治疗小鼠的肿瘤生长和 PTX 抗性。miR-137 被证实为 HULC 的靶点，并直接靶向 ITGB8。并且 HULC 敲低通过靶向 miR-137 下调 ITGB8 表达。miR-137 抑制剂或 ITGB8 过表达减轻了 HULC 敲低对 PTX 抗性的抑制影响。总的来说，HULC 通过海绵 miR-137 调节 ITGB8 表达以促进 OC 的 PTX 抗性。miR-137 抑制剂或 ITGB8 过表达减轻了 HULC 敲低对 PTX 抗性的抑制影响。总的来说，HULC 通过海绵 miR-137 调节 ITGB8 表达以促进 OC 的 PTX 抗性。miR-137 抑制剂或 ITGB8 过表达减轻了 HULC 敲低对 PTX 抗性的抑制影响。总的来说，HULC 通过海绵 miR-137 调节 ITGB8 表达以促进 OC 的 PTX 抗性。