ANKRD22 promotes progression of non-small cell lung cancer through transcriptional up-regulation of E2F1.
ANKRD22 promotes progression of non-small cell lung cancer through transcriptional up-regulation of E2F1.
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ANKRD22通过E2F1转录上调促进非小细胞肺癌的进展
DOI：
10.1038/s41598-017-04818-y
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发表时间：
2017-06-30
影响因子：
4.6
通讯作者：
Zhao J
中科院分区：
文献类型：
--
作者：
Yin J;Fu W;Dai L;Jiang Z;Liao H;Chen W;Pan L;Zhao J
由于肿瘤快速进展和复发，肺癌是所有恶性肿瘤中死亡的主要原因;然而，肿瘤进展的潜在分子机制尚不清楚。在本研究中，我们确定ANKRD 22作为一个新的肿瘤相关基因在非小细胞肺癌（NSCLC）。根据临床相关性分析，ANKRD 22在原发癌组织中的表达高于癌旁组织，且ANKRD 22的高表达水平与复发和总生存期短显著相关。敲除和过表达分析显示，ANKRD 22通过增加细胞增殖促进肿瘤进展。在异种移植试验中，敲低ANKRD 22或用ANKRD 22 siRNA体内处理抑制肿瘤生长。此外，ANKRD 22被证明参与E2 F1的转录调控，并且ANKRD 22通过上调E2 F1的表达促进细胞增殖，从而促进细胞周期进程。因此，我们的研究表明ANKRD 22上调E2 F1的转录，并通过促进细胞增殖促进NSCLC的进展。这些发现表明ANKRD 22可能作为NSCLC的新治疗靶点。
Lung cancer is the leading cause of death among all malignancies due to rapid tumor progression and relapse; however, the underlying molecular mechanisms of tumor progression are unclear. In the present study, we identified ANKRD22 as a novel tumor-associated gene in non-small cell lung cancer (NSCLC). According to the clinical correlation analysis, ANKRD22 was highly expressed in primary cancerous tissue compared with adjacent cancerous tissue, and high expression levels of ANKRD22 were significantly correlated with relapse and short overall survival time. Knockdown and overexpression analysis revealed that ANKRD22 promoted tumor progression by increasing cell proliferation. In xenograft assays, knockdown of ANKRD22 orin vivotreatment with ANKRD22 siRNA inhibited tumor growth. Furthermore, ANKRD22 was shown to participate in the transcriptional regulation of E2F1, and ANKRD22 promoted cell proliferation by up-regulating the expression of E2F1 which enhanced cell cycle progression. Therefore, our studies indicated that ANKRD22 up-regulated the transcription of E2F1 and promoted the progression of NSCLC by enhancing cell proliferation. These findings suggest that ANKRD22 could potentially act as a novel therapeutic target for NSCLC.