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KIAA1522 Promotes Colorectal Carcinoma Liver Metastases via Activation of the Notch Signaling Pathway

ABSTRACT: Purpose: Our research aims to identify the expression, clinical value, biological significance and signaling pathway of KIAA1522 in colorectal carcinoma liver metastases (CRLM). Materials and Methods: To elucidate the role of KIAA1522 in CRC, its expression and survival analysis were assessed using GEPIA databases. Then we evaluated expression of KIAA1522 immunohistochemically in tissue samples of 57 patients with CRLM. The correlations between expression of KIAA1522 and clinical significance, prognosis of these 57 patients with CRLM were analyzed. Western blotting, CCK-8, colony formation, Flow cytometry, Transwell invasion, and wound healing assays were performed to explore the function of KIAA1522 in colon cancer cell lines. Finally, transcriptome sequencing and gene set enrichment analysis was used to identify the pathways involved. Results: Our results demonstrated that KIAA1522 was highly expressed in CRLM tissues and colon cancer cell lines, and expression of KIAA1522 in primary sites was significantly positively correlated with that in metastatic sites. Furthermore, KIAA1522 overexpression was associated with unfavorable clinicopathological characteristics. Survival analyses revealed that KIAA1522 overexpression predicted lower overall survival rates in patients with CRLM. Functional studies suggested that KIAA1522 facilitated proliferation, migration and invasion of colon cancer cell lines in vitro. Moreover, KIAA1522 upregulated the Notch signaling pathway, as confirmed by transcriptome sequencing and gene set enrichment analysis. Conclusion: In conclusion, these data suggest that upregulation of KIAA1522 might enhance tumorigenicity and metastasis of colon cancer cell lines through potentiating the Notch signaling pathway activity. Expression of KIAA1522 plays oncogenic roles in CRLM and might serve as a novel molecular target in CRLM treatment.

ORGANISM(S): Homo

PROVIDER: GSE174449 | GEO | 2022/12/31

REPOSITORIES: GEO

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Project description:Background: JAG-1 is a ligand of Notch signaling and can regulate cell differentiation and proliferation in cancers. Recent studies indicated that JAG1 is a gene associated with cancer progression. Therefore, we investigated the role of JAG1 in lung cancer progression. Methods: The expression of JAG1 was manipulated by overexpression or RNA silencing in several human lung cell lines. The effect of JAG1 on tumorigenesis and invasion was assessed by the cell anchorage-independent growth, cell proliferation, cell migration and invasion assays in vitro as well as metastasis in vivo. The potential downstream genes of JAG1 were identified by oligonucleotide microarrays and quantitative reverse transcriptionÂ¡Vpolymerase chain reaction (RT-PCR). We further measured JAG1 expression in lung cancer specimens by RT-PCR. Correlation between JAG1 expression and overall survival of lung cancer patients was determined by using the log-rank test and multivariable Cox proportional hazards regression analysis. All statistical tests were two-sided. Results: JAG1 enhanced anchorage-independent growth, cell migration, invasion in the lower invasive cells, CL1-0. JAG1 also increased the capability of migration and invasion in the other two lung cancer cell lines (A549 and NCI-H226). The silencing of JAG1 inhibited migration and invasion activities of the higher invasive cells, CL1-5, by siRNA technology. The invasion-promoting activity of JAG1 was also demonstrated in vivo by using a mouse metastasis model. By microarray analysis, we found that the expression of heat shock 70kDa protein 2 (HSPA2) was activated by JAG1 overexpression and eliminated by JAG1 silencing. Moreover, lung cancer patients with high JAG1 expressing tumors had shorter overall survival than those with low-expressing tumors. Conclusion: JAG1 might be an oncogene which promotes colonogenesis and metastasis, and high JAG1 expression is associated with shorten survival in lung cancer. In this investigation, we used a lung cancer invasion cell model to identify the genes involved in cancer progression. JAG1 is a potential oncogene whose expression is correlated to the survival of patients with breast, prostate and liver cancers. However, the role of JAG1 in lung caner progression has not been reported, particularly in metastasis. Here, JAG1 was ectopically expressed in lower invasive lung cancer cell line its impact on colonogenesis, migration and invasiveness was assessed. The underlying mechanism was explored by JAG1-expressed transfectants and microarrays and the clinical relevance was evaluated by quantitative RT-PCR.

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KIAA1522 Promotes Colorectal Carcinoma Liver Metastases via Activation of the Notch Signaling Pathway

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