Department of Chest Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, Guangdong, China.
Sci Rep. 2017 Jun 30;7(1):4430. doi: 10.1038/s41598-017-04818-y.
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 or in vivo treatment 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.
肺癌是所有恶性肿瘤中导致死亡的主要原因，这是由于肿瘤的快速进展和复发；然而，肿瘤进展的潜在分子机制尚不清楚。在本研究中，我们鉴定了 ANKRD22 是一种非小细胞肺癌（NSCLC）中的新型肿瘤相关基因。根据临床相关性分析，ANKRD22 在原发性癌组织中的表达明显高于癌旁组织，并且 ANKRD22 的高表达水平与复发和总生存期短显著相关。敲低和过表达分析表明，ANKRD22 通过增加细胞增殖促进肿瘤进展。在异种移植实验中，ANKRD22 的敲低或体内 ANKRD22 siRNA 的治疗抑制了肿瘤生长。此外，ANKRD22 被证明参与 E2F1 的转录调控，并且 ANKRD22 通过上调 E2F1 的表达促进细胞增殖，从而增强细胞周期进程。因此，我们的研究表明，ANKRD22 通过增强细胞增殖而上调 E2F1 的转录，从而促进 NSCLC 的进展。这些发现表明，ANKRD22 可能成为 NSCLC 的一种新的治疗靶点。
