LncRNA HOTAIR promotes the invasion and metastasis of oral squamous cell carcinoma through metastasis‐associated gene 2

Abstract

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.

Circular RNA circ-NCOR2 accelerates papillary thyroid cancer progression by sponging miR-516a-5p to upregulate metastasis-associated protein 2 expression

“… 24 Moreover, MTA2 expression is regulated at the posttransciptional level in gastric cancer, 25 and the long noncoding RNA HOTAIR promotes the invasion and metastasis of oral squamous cell carcinoma through targeting MTA2. 26 …”

Roles of the HOX Proteins in Cancer Invasion and Metastasis

“…Recent findings have also related HOTAIR interference to Trastuzumab resistance in GC, through the sponging of miR-3030 and consequent upregulation of ERBB4 [133], which is responsible for activating the PI3K/ATK signalling pathway [134]. Several HOTAIR-dependent interferences in miR pathways have also been described in glioma [123], HCC [135][136][137] prostate cancer [138,139] and squamous cell carcinomas [140][141][142][143].…”

Long Noncoding RNAs in the Metastasis of Oral Squamous Cell Carcinoma

“…Beyond that, the inhibition of miR-21 by GAS5 also increased the expression of E-cadherin, while decreased the expression of N-cadherin, Vimentin, and Snail, suggesting that the EMT of OSCC cells was repressed as well ( 36 ). The results of another study showed that HOTAIR can improve the expression of MTA2 (metastasis-associated gene 2) via the miR-326/MTA2 axis, thereby facilitating the migration, invasion, and EMT of OSCC cells ( 43 ). Similarly, lncRNA CASC15 (cancer susceptibility candidate 15) has also played a role in promoting metastasis in the development of OSCC.…”