Despite therapeutic advancements, there has been little improvement in the survival status of patients with oral squamous cell carcinoma (OSCC). HOX antisense intergenic RNA (HOTAIR) has been shown to be dysregulated in several cancer types. However, the roles of HOTAIR in OSCC remain largely unknown. In this study, we investigated the association of HOTAIR expression with clinicopathological features in OSCC patients and the crucial roles of HOTAIR in the modulation of tumor progression. Our results showed that HOTAIR was highly expressed both in OSCC tissue samples and cell lines compared with corresponding normal oral mucosa tissues and human oral keratinocytes. Its overexpression was positively correlated with TNM (tumor-node-metastases) stage, histological grade, and regional lymph node metastasis. The knockdown of HOTAIR by short hairpin RNA significantly decreased the migration, invasion, and epithelial-mesenchymal transition of OSCC cells in vitro. Moreover, there was a negative correlation between HOTAIR and microRNA-326 expression in OSCC tissue samples and cell lines. Luciferase reporter and loss-of-function assays revealed that HOTAIR acted as a competitive endogenous RNA effectively sponging miR-326, thereby regulating the derepression of metastasis-associated gene 2 (MTA2). Finally, the expression and clinical significance of MTA2 were analyzed in another cohort of OSCC tissue samples. High MTA2 expression was significantly correlated with clinicopathological features of advanced OSCC and poor prognosis for patients with OSCC. Collectively, HOTAIR overexpression promoted the progression of OSCC. The HOTAIR-miR-326-MTA2 axis may contribute to a better understanding of OSCC pathogenesis and be a potential therapeutic target for OSCC.

中文翻译：

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LncRNA HOTAIR通过转移相关基因2促进口腔鳞状细胞癌的侵袭和转移。

尽管治疗取得了进步，但口腔鳞状细胞癌（OSCC）患者的生存状况几乎没有改善。HOX反义基因间RNA（HOTAIR）已显示在几种癌症类型中失调。但是，HOTAIR在OSCC中的作用仍然未知。在这项研究中，我们调查了OSCC患者中HOTAIR表达与临床病理特征的关系以及HOTAIR在调节肿瘤进展中的关键作用。我们的结果表明，与相应的正常口腔粘膜组织和人类口腔角质形成细胞相比，HOTAIR在OSCC组织样品和细胞系中均高表达。其过表达与TNM（肿瘤淋巴结转移）阶段，组织学分级和区域淋巴结转移呈正相关。短发夹RNA敲除HOTAIR可以显着降低体外OSCC细胞的迁移，侵袭和上皮间质转化。此外，在OSCC组织样品和细胞系中HOTAIR和microRNA-326表达之间存在负相关。萤光素酶报告基因和功能丧失分析表明，HOTAIR可以作为竞争性内源RNA，有效地使miR-326海绵化，从而调节转移相关基因2（MTA2）的抑制。最后，在另一组OSCC组织样品中分析了MTA2的表达和临床意义。MTA2高表达与晚期OSCC的临床病理特征和OSCC患者的预后差显着相关。总之，HOTAIR的过表达促进了OSCC的发展。