Yi Xin, Hu Conghui, Zhang Chen, Shao Kai, Sun Hui, Jiang Yuanhui, Sun Nianfeng, Zhi Xuting
Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Wenhua Road, Jinan, Shandong 250012, China; Department of General Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong 2660035, China.
Department of Endocrinology and Metabolism, Qingdao Women and Children's Hospital, Qingdao University, 6 Tongfu Road, Qingdao, Shandong 266034, China.
Cell Signal. 2022 Feb;90:110202. doi: 10.1016/j.cellsig.2021.110202. Epub 2021 Nov 23.
Our research was absorbed into exploring the expression, clinicopathological value, biological significance and signaling pathway of KIAA1522 in colorectal carcinoma and its distant metastasis.
The expression of KIAA1522 and survival analysis in colorectal carcinoma (CRC) were assessed using GEPIA databases. Then we evaluated the expression of KIAA1522 immunohistochemically in tissue samples of 57 patients with colorectal carcinoma liver metastasis (CRLM). The correlations between the expression of KIAA1522, clinical significance and prognosis of these 57 patients with CRLM were analyzed. The migration and invasion of KIAA1522 were explored by western blotting, CCK-8, colony formation, flow cytometry, wound healing assays and transwell invasion in vitro and tail vein injection models in vivo. Then, transcriptome sequencing and gene set enrichment analysis was performed to identify the signaling pathways involved, while western blotting analysis and immunohistochemistry (IHC) were used to identify the expression of key genes in Notch signaling.
KIAA1522 was overexpressed in CRLM tissues and colon cancer cell lines, and the expression of KIAA1522 in metastatic sites was positively correlated with that in primary sites. In addition, the overexpression of KIAA1522 is associated with poor clinicopathological features. Survival analysis showed that the overexpression of KIAA1522 predicted a low overall survival rate in patients with CRLM. Functional studies suggested that KIAA1522 promotes the proliferation, invasion and migration of colon carcinoma in vitro. KIAA1522 could promote distant metastasis of CRC in vivo. Moreover, KIAA1522 upregulated the Notch signaling pathway in colorectal cancer cell lines in vitro and lung metastatic nodes in vivo.
In conclusion, it is suggested that the upregulation of KIAA1522 might promote the tumorigenicity and metastasis of colorectal carcinoma through Notch signaling pathway. KIAA1522 plays a carcinogenic role in the metastasis of colorectal carcinoma and might serve as a new molecular target for the treatment.
我们的研究致力于探索KIAA1522在结直肠癌及其远处转移中的表达、临床病理价值、生物学意义和信号通路。
利用GEPIA数据库评估结直肠癌（CRC）中KIAA1522的表达及生存分析。随后，我们通过免疫组织化学方法评估了57例结直肠癌肝转移（CRLM）患者组织样本中KIAA1522的表达。分析了这57例CRLM患者中KIAA1522的表达、临床意义与预后之间的相关性。通过蛋白质免疫印迹法、CCK-8法、集落形成实验、流式细胞术、伤口愈合实验以及体外transwell侵袭实验和体内尾静脉注射模型，探究KIAA1522的迁移和侵袭能力。然后，进行转录组测序和基因集富集分析以确定相关信号通路，同时利用蛋白质免疫印迹分析和免疫组织化学（IHC）来鉴定Notch信号通路中关键基因的表达。
KIAA1522在CRLM组织和结肠癌细胞系中高表达，且其在转移部位的表达与原发部位呈正相关。此外，KIAA1522的过表达与不良临床病理特征相关。生存分析表明，KIAA1522的过表达预示着CRLM患者的总生存率较低。功能研究表明，KIAA1522在体外可促进结肠癌的增殖、侵袭和迁移。KIAA1522在体内可促进CRC的远处转移。此外，KIAA1522在体外结肠癌细胞系和体内肺转移结节中上调了Notch信号通路。
总之，提示KIAA1522的上调可能通过Notch信号通路促进结直肠癌的致瘤性和转移。KIAA1522在结直肠癌转移中发挥致癌作用，可能成为新的治疗分子靶点。
