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LncRNA-XIST promotes the oxidative stress-induced migration, invasion, and epithelial-to-mesenchymal transition of osteosarcoma cancer cells through miR-153-SNAI1 axis.
Cell Biology International ( IF 3.9 ) Pub Date : 2020-06-09 , DOI: 10.1002/cbin.11405
Ji-Feng Wen 1 , Yong-Qing Jiang 2 , Chao Li 2 , Xian-Kui Dai 2 , Tong Wu 2 , Wen-Zhe Yin 2
Affiliation  

Osteosarcoma (OS) is the most common type of primary bone tumor that exhibits invasive growth and long‐distance organ metastasis. Thus, investigating the specifically targeted therapeutic agents against metastatic osteosarcoma depends on understanding the molecular mechanisms. The long noncoding RNAs (lncRNA) XIST (X‐inactive specific transcript) has been reported to have oncogenic roles in various malignant tumors including OS. However, its molecular mechanisms in OS migration and invasion are still under investigation. In the current study, we demonstrate that XIST is significantly upregulated in 30 pairs of OS tissues compared with their matched adjacent nontumor tissues by the quantitative reverse transcription polymerase chain reaction. Overexpression of XIST significantly induced the invasion, migration, and the epithelial‐to‐mesenchymal transition (EMT) phenotype. The epithelial marker, E‐cadherin was effectively suppressed by XIST overexpression. On the other way, the mesenchymal marker, Fibronectin, Snail, and Vimentin were significantly activated by exogenous XIST overexpression. Furthermore, we observed XIST was upregulated by the oxidative stress‐induced EMT. Bioinformatical analysis indicated that miR‐153 has multiple biding sites for XIST and miR‐153 was inversely suppressed by oxidative stress. XIST was verified to directly downregulate miR‐153 via sponging. We identified the mesenchymal marker, SNAI1 was a direct messenger RNA target of miR‐153. Importantly, inhibiting XIST successfully blocked the H2O2‐induced EMT of OS cells. In conclusion, this work demonstrates that lncRNA‐XIST promotes the oxidative stress‐induced OS cell invasion, migration, and EMT through the miR‐153/SNAI1 pathway, presenting lncRNA‐XIST as a promising therapeutic target for treating metastatic OS.

中文翻译:

LncRNA-XIST通过miR-153-SNAI1轴促进氧化应激诱导的骨肉瘤癌细胞迁移、侵袭和上皮间质转化。

骨肉瘤(OS)是最常见的原发性骨肿瘤类型,具有侵袭性生长和远距离器官转移。因此,研究针对转移性骨肉瘤的特异性靶向治疗药物取决于对分子机制的了解。据报道,长非编码 RNA(lncRNA)XIST(X 失活特异性转录物)在包括 OS 在内的各种恶性肿瘤中具有致癌作用。然而,其在 OS 迁移和侵袭中的分子机制仍在研究中。在目前的研究中,我们通过定量逆转录聚合酶链反应证明 XIST 在 30 对 OS 组织中与其匹配的相邻非肿瘤组织相比显着上调。XIST 的过表达显着诱导了侵袭、迁移、和上皮间质转化(EMT)表型。XIST 过表达有效抑制了上皮标志物 E-钙粘蛋白。另一方面,间充质标记物、纤连蛋白、蜗牛和波形蛋白被外源性 XIST 过表达显着激活。此外,我们观察到 XIST 被氧化应激诱导的 EMT 上调。生物信息学分析表明 miR-153 具有多个 XIST 结合位点,并且 miR-153 被氧化应激反向抑制。XIST 经证实可通过海绵作用直接下调 miR-153。我们确定了间充质标记,SNAI1 是 miR-153 的直接信使 RNA 靶标。重要的是,抑制 XIST 成功地阻止了 H 间充质标记物、纤连蛋白、Snail 和波形蛋白被外源性 XIST 过表达显着激活。此外,我们观察到 XIST 被氧化应激诱导的 EMT 上调。生物信息学分析表明 miR-153 具有多个 XIST 结合位点,并且 miR-153 被氧化应激反向抑制。XIST 经证实可通过海绵作用直接下调 miR-153。我们确定了间充质标记,SNAI1 是 miR-153 的直接信使 RNA 靶标。重要的是,抑制 XIST 成功地阻止了 H 间充质标记物、纤连蛋白、Snail 和波形蛋白被外源性 XIST 过表达显着激活。此外,我们观察到 XIST 被氧化应激诱导的 EMT 上调。生物信息学分析表明 miR-153 具有多个 XIST 结合位点,并且 miR-153 被氧化应激反向抑制。XIST 经证实可通过海绵作用直接下调 miR-153。我们确定了间充质标记,SNAI1 是 miR-153 的直接信使 RNA 靶标。重要的是,抑制 XIST 成功地阻止了 H 生物信息学分析表明 miR-153 具有多个 XIST 结合位点,并且 miR-153 被氧化应激反向抑制。XIST 经证实可通过海绵作用直接下调 miR-153。我们确定了间充质标记,SNAI1 是 miR-153 的直接信使 RNA 靶标。重要的是,抑制 XIST 成功地阻止了 H 生物信息学分析表明 miR-153 具有多个 XIST 结合位点,并且 miR-153 被氧化应激反向抑制。XIST 经证实可通过海绵作用直接下调 miR-153。我们确定了间充质标记,SNAI1 是 miR-153 的直接信使 RNA 靶标。重要的是,抑制 XIST 成功地阻止了 H2 O 2诱导的 OS 细胞 EMT。总之,这项工作表明 lncRNA-XIST 通过 miR-153/SNAI1 通路促进氧化应激诱导的 OS 细胞侵袭、迁移和 EMT,表明 lncRNA-XIST 是治疗转移性 OS 的有希望的治疗靶点。
更新日期:2020-06-09
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