| Autor: |
Kaifeng Zheng, Qiang Yu, Yujie Zhao, Lingying Zhao, Hanwei Cao, Jingzhou Xiang, Wenqing Zhang, Yan-yan Zhan, Xiaoting Hong, Tianhui Hu, Li Xiao |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
SSRN Electronic Journal. |
| ISSN: |
1556-5068 |
| Popis: |
Background: Unc-51-like kinases 1 (ULK1) plays an important role in the development of tumors but its roles remains largely unknown. The clinical and biological significance of ULK1 in colon cancer remains unclear. Methods: The expression ULK1 were initially assessed by meta‑analysis in the Oncomine database and TCGA analysis, followed by the validations in two independent colon cancer patient cohorts. A functional characterization of ULK1 in colon cancer was examined by targeted gene silencing in colon cancer cell lines and a xenograft animal model. Transcriptome analysis was used to explore the genetic changes in the transcriptome of ULK1 silencing. Findings: Meta-analysis revealed that increased ULK1 mRNA expression was associated with colon cancer as compared with the normal colon tissues. In our original cohort of colon cancer patients, ULK1 was also upregulated significantly in colon cancer and was significantly associated with tumor size and invasion depth as well as worse overall survival. Further multivariate analysis showed that ULK1 expression remained an independent prognostic factor for survival. Knockdown of ULK1 led to suppressed proliferation in colon cancer cell lines, as well as in the xenograft animal model. The transcriptome analysis showed that inhibition of ULK1 significantly changes the expression of the genes relate to ErbB signaling pathway. Further studies demonstrate that inactivation of ULK1 significantly decrease EGFR levels in vivo and in vitro. Interpretation: These observations strongly indicate a novel evidence for the oncogenic role of ULK1 and suggest that it can serve as a useful marker for the prognosis of colon cancer and an oncogenic EGFR regulator in the development of colon cancer. Funding Statement: This work was supported by the National Natural Science Foundation of China (No. 81802640, 31770860, 81572589, 81602560), the Natural Science Foundation of Fujian Province (2018J01400, 2018R1101), the Health and young middle-aged of personnel training project funding of Fujian Province (2016-ZQN-89) and Scientific Research Projects for Overseas Students in Xiamen City. Declaration of Interests: The authors declare no conflict of interests. Ethics Approval Statement: All animals were performed in accordance with a protocol approved by the Animal Care and Use Committee of Xiamen University. This study was approved by the Medical Ethics Committee of Zhongshan Hospital Affiliated to Xiamen University in accordance with the Helsinki Declaration and conducted with the informed consent of all patients. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
