Data from Circadian Clock Gene <i>Bmal1</i> Inhibits Tumorigenesis and Increases Paclitaxel Sensitivity in Tongue Squamous Cell Carcinoma

Abstract

&lt;div&gt;Abstract&lt;p&gt;Circadian clock genes regulate cancer development and chemotherapy susceptibility. Accordingly, chronotherapy based on circadian phenotypes might be applied to improve therapeutic efficacy. In this study, we investigated whether the circadian clock gene &lt;i&gt;Bmal1&lt;/i&gt; inhibited tumor development and increased paclitaxel sensitivity in tongue squamous cell carcinoma (TSCC). Bmal1 expression was downregulated and its rhythmic pattern of expression was affected in TSCC samples and cell lines. Ectopic Bmal1 inhibited cell proliferation, migration and invasion &lt;i&gt;in vitro&lt;/i&gt;, and tumor growth in mouse xenograft models of TSCC. After exposure to paclitaxel, Bmal1-overexpressing cells displayed a relative increase in apoptosis and were more susceptible to paclitaxel treatment &lt;i&gt;in vivo&lt;/i&gt;. Mechanistic investigations suggested a regulatory connection between Bmal1, TERT, and the oncogenic transcriptional repressor EZH2 (enhancer of zeste homolog 2), the recruitment of which to the &lt;i&gt;TERT&lt;/i&gt; promoter increased paclitaxel-induced apoptosis and cell growth inhibition. Clinically, paclitaxel efficacy correlated positively with Bmal1 expression levels in TSCC. Overall, our results identified &lt;i&gt;Bmal1&lt;/i&gt; as a novel tumor suppressor gene that elevates the sensitivity of cancer cells to paclitaxel, with potential implications as a chronotherapy timing biomarker in TSCC. &lt;i&gt;Cancer Res; 77(2); 532–44. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;