Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Dis Markers. 2022 Jun 2;2022:5772089. doi: 10.1155/2022/5772089. eCollection 2022.
Previous studies have suggested an association of the expression of activating transcription factor-2 (ATF-2) with the survival time and the activity of the Wnt/Ca signaling pathway in non-small-cell lung cancer (NSCLC). However, the exact role of ATF-2 in tumorigenesis and its underlying mechanism remains unclear. In this study, we study whether ATF-2 regulates the growth and reproduction of NSCLC cells through the Wnt/Ca pathway. The expression of ATF-2 and pathway-related genes in non-small-cell lung cancer was detected by qRT-PCR and Western blotting. CRISPR/Cas9 technology was used to knock out the ATF-2 gene, and pathway inhibitors and agonists were added to induce cultured cells. The expression of pathway genes and the proliferation and invasion ability of A549 lung cancer cells were analyzed. ATF-2 and pathway-related genes were upregulated in NSCLC. The proliferation and invasion ability of A549 lung cancer cells was decreased after only adding pathway inhibitors. The expression of Wnt/Ca pathway protein was decreased when the ATF-2 gene was knocked out, but the expression of Wnt/Ca pathway protein was reversed after the addition of a pathway agonist. These results suggest that ATF-2 acts as an agonist in the Wnt/Ca signaling pathway, promoting the expression of Wnt5a, Wnt11, CaMK II, and NLK in the Wnt/Ca pathway, thereby regulating the proliferation and invasion of NSCLC cells.
先前的研究表明，激活转录因子-2（ATF-2）的表达与非小细胞肺癌（NSCLC）的生存时间和 Wnt/Ca 信号通路的活性有关。然而，ATF-2 在肿瘤发生中的确切作用及其潜在机制尚不清楚。在这项研究中，我们研究了 ATF-2 是否通过 Wnt/Ca 通路调节 NSCLC 细胞的生长和繁殖。通过 qRT-PCR 和 Western blot 检测非小细胞肺癌中 ATF-2 和通路相关基因的表达。利用 CRISPR/Cas9 技术敲除 ATF-2 基因，并添加通路抑制剂和激动剂诱导培养细胞。分析通路基因的表达以及 A549 肺癌细胞的增殖和侵袭能力。在 NSCLC 中，ATF-2 和通路相关基因上调。仅添加通路抑制剂后，A549 肺癌细胞的增殖和侵袭能力下降。敲除 ATF-2 基因后，Wnt/Ca 通路蛋白的表达减少，但添加通路激动剂后，Wnt/Ca 通路蛋白的表达逆转。这些结果表明，ATF-2 在 Wnt/Ca 信号通路中充当激动剂，促进 Wnt/Ca 通路中 Wnt5a、Wnt11、CaMK II 和 NLK 的表达，从而调节 NSCLC 细胞的增殖和侵袭。
