KIAA1199 通过 Wnt/β-catenin 通路和 MMPs 介导的 EMT 进展促进迁移和侵袭，并作为胃癌的预后不良标志物。
KIAA1199 promotes migration and invasion by Wnt/β-catenin pathway and MMPs mediated EMT progression and serves as a poor prognosis marker in gastric cancer.
机构信息
Laboratory of Surgery, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
Center for Molecular Diagnosis, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
出版信息
PLoS One. 2017 Apr 19;12(4):e0175058. doi: 10.1371/journal.pone.0175058. eCollection 2017.
BACKGROUND
KIAA1199 was upregulated in diverse cancers, but the association of KIAA1199 with gastric cancer (GC), the biological role of KIAA1199 in GC cells and the related molecular mechanisms remain to be elucidated.
METHODS
KIAA1199 expression was analysed by reverse transcription-polymerase chain reaction assay (RT-PCR) and immunohistochemistry (IHC) in GC patient tissue. The small hairpin RNA (shRNA) was applied for the knockdown of endogenous KIAA1199 in NCI-N87 and AGS cells. MTT, colony formation, scratch wounding migration, transwell chamber migration and invasion assays were employed respectively to investigate the role of KIAA1199 in GC cells. The potential signaling pathway of KIAA1199 induced migration and invasion was detected.
RESULTS
KIAA1199 was upregulated in GC tissue and was an essential independent marker for poor prognosis. Knockdown KIAA1199 suppressed the proliferation, migration and invasion in GC cells. KIAA1199 stimulated the Wnt/β-catenin signaling pathway and the enzymatic activity of matrix metalloproteinase (MMP) family members and thus accelerated the epithelial-to-mesenchymal transition (EMT) progression in GC cells.
CONCLUSION
These findings demonstrated that KIAA1199 was upregulated in GC tissue and associated with worse clinical outcomes in GC, and KIAA1199 acted as an oncogene by promoting migration and invasion through the enhancement of Wnt/β-catenin signaling pathway and MMPs mediated EMT progression in GC cells.
背景
KIAA1199 在多种癌症中上调，但 KIAA1199 与胃癌（GC）的关联、KIAA1199 在 GC 细胞中的生物学作用以及相关的分子机制仍有待阐明。
方法
通过逆转录聚合酶链反应（RT-PCR）和免疫组织化学（IHC）分析 GC 患者组织中的 KIAA1199 表达。小发夹 RNA（shRNA）用于敲低 NCI-N87 和 AGS 细胞中的内源性 KIAA1199。MTT、集落形成、划痕愈合迁移、Transwell 室迁移和侵袭实验分别用于研究 KIAA1199 在 GC 细胞中的作用。检测了 KIAA1199 诱导迁移和侵袭的潜在信号通路。
结果
KIAA1199 在 GC 组织中上调，是预后不良的重要独立标志物。敲低 KIAA1199 抑制了 GC 细胞的增殖、迁移和侵袭。KIAA1199 刺激 Wnt/β-catenin 信号通路和基质金属蛋白酶（MMP）家族成员的酶活性，从而加速 GC 细胞的上皮-间质转化（EMT）进程。
结论
这些发现表明，KIAA1199 在 GC 组织中上调，与 GC 的临床结局较差相关，并且 KIAA1199 通过增强 Wnt/β-catenin 信号通路和 MMP 介导的 EMT 进程促进迁移和侵袭，发挥癌基因的作用。
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