Scientific Research Centre, the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin 150081, China.
Int J Biochem Cell Biol. 2024 Nov;176:106666. doi: 10.1016/j.biocel.2024.106666. Epub 2024 Sep 27.
Oncogene amplification is a significant factor contributing to poor prognosis and limited treatment in patients with advanced gastric cancer. Therefore, identifying amplified oncogenes and elucidating their oncogenic mechanisms will provide reliable therapeutic targets for the clinical treatment of gastric cancer. In this study, we identify a high amplification of 17q12, which includes five oncogenes that are co-amplified and co-overexpressed with ERBB2 using array comparative genomic hybridization, with migration and invasion enhancer 1 (MIEN1) being particularly highlighted for its clinical significance, function, and role in gastric cancer progression. By detecting MIEN1 copy number and expression level across eight gastric cancer cell lines and in tissue microarrays from 543 primary gastric cancer tissues, we found that MIEN1 amplification and overexpression correlated with sex and Lauren's intestinal type classification of gastric cancer. Besides that, elevated MIEN1 expression was associated with poorer patient survival. In vitro experiments have shown that MIEN1 overexpression enhanced cell proliferation, invasion, and migration, whereas MIEN1 knockdown reversed these malignant phenotypes in vitro. Furthermore, MIEN1 knockdown inhibited tumorigenesis and metastasis of gastric cancer cells in nude mice. Mechanistically, MIEN1 activates the IL-6/JAK2/STAT3 signaling pathway, which drives the proliferation, invasion, and migration of gastric cancer cells. This study demonstrates that MIEN1 contributes to the malignant behavior of gastric cancer through the IL-6/JAK2/STAT3 pathway, suggesting that MIEN1 could serve as a valuable therapeutic target for gastric cancer.
癌基因扩增是导致晚期胃癌患者预后不良和治疗受限的重要因素。因此，鉴定扩增的癌基因并阐明其致癌机制将为胃癌的临床治疗提供可靠的治疗靶点。在这项研究中，我们通过阵列比较基因组杂交技术鉴定出 17q12 的高扩增，其中包括五个与 ERBB2 共同扩增和过表达的癌基因，迁移和侵袭增强因子 1（MIEN1）因其在胃癌进展中的临床意义、功能和作用而尤为突出。通过检测 8 种胃癌细胞系和 543 例原发性胃癌组织的组织微阵列中的 MIEN1 拷贝数和表达水平，我们发现 MIEN1 扩增和过表达与胃癌的性别和 Lauren 的肠型分类相关。此外，MIEN1 表达水平升高与患者生存不良相关。体外实验表明，MIEN1 过表达增强了细胞的增殖、侵袭和迁移能力，而 MIEN1 敲低则在体外逆转了这些恶性表型。此外，MIEN1 敲低抑制了裸鼠胃癌细胞的致瘤性和转移。在机制上，MIEN1 通过激活 IL-6/JAK2/STAT3 信号通路，促进胃癌细胞的增殖、侵袭和迁移。这项研究表明，MIEN1 通过 IL-6/JAK2/STAT3 通路促进胃癌的恶性行为，提示 MIEN1 可能成为胃癌治疗的有价值的靶点。
