结直肠癌中SENP1和RNF4依赖苏木化调节ZNF281的降解

结直肠癌中SENP1和RNF4依赖苏木
化调节ZNF281的降解
摘要
目的：探究结直肠癌中SENPl和RNF4对ZNF281的调节机制及其在肿瘤发生、发展中的作用。

方法：使用siRNA靶向剪断SENPl和RNF4基因表达，通过Western blotting和免疫荧光染色检测ZNF281蛋白水平以及
先后用体外肿瘤细胞“裸核体”组分、GST-tagged ZNF281RIZ 域蛋白进行in vitro SUMOylation实验，确定了SENPl-RNF4
模块调节ZNF281的SUMO修饰和降解的机制。

结果：在结直肠癌组织标本中，SENPl和RNF4表达明显升高，而ZNF281蛋白表达水平也随之升高。

实验证明，SENPl和
RNF4可通过调节ZNF281的SUMO修饰而影响其降解。

同时，ZNF281的几个保守Lys位点序列是SENPl调节SUMOylation
的靶点。

在体内注射SENPl和RNF4与肿瘤相关的miRNA后，
肿瘤细胞增殖显著减缓，肿瘤体积也显著减小。

结论：SENPl-RNF4调节ZNF281的SUMOylation及降解，参与
肿瘤细胞的增殖、转移和耐药性的调控，是结直肠癌治疗和预防的潜在靶点。

关键词：结直肠癌、SENPl、RNF4、SUMOylation、ZNF281
Abstract
Objective: To investigate the regulatory mechanism of SENPl and RNF4 on ZNF281 and their role in the occurrence and development of colorectal cancer.
Methods: siRNA was used to target SENPl and RNF4 gene expression, and the protein level of ZNF281 was detected by Western blotting and immunofluorescence staining. In vitro SUMOylation experiments were performed using naked nuclei and GST-tagged ZNF281RIZ domain protein to determine the mechanism by which the SENPl-RNF4 module regulates ZNF281 SUMOylation and degradation.
Results: In colorectal cancer tissue samples, the expression of SENPl and RNF4 was significantly increased, and the protein expression level of ZNF281 also increased. The results of the experiment showed that SENPl and RNF4 can affect the degradation of
ZNF281 by regulating its SUMOylation. At the same time, several conserved Lys site sequences of ZNF281 are the targets of SENPl regulation of SUMOylation. After injection of miRNA related to SENPl and RNF4 in vivo, the proliferation of tumor cells was significantly reduced, and the tumor volume was significantly
reduced.
Conclusion: SENPl-RNF4 regulates ZNF281 SUMOylation and degradation, participates in the regulation of tumor cell proliferation, migration and drug resistance, and is a potential target for the prevention and treatment of colorectal cancer.
Keywords: colorectal cancer, SENPl, RNF4, SUMOylation, ZNF28
Colorectal cancer is a common malignant tumor that seriously threatens human health. In recent years, the role of protein modification in the development of cancer has attracted more and more attention. SUMOylation is a post-translational modification process that plays an important role in cellular physiological and pathological processes, including DNA repair, transcriptional regulation, and protein degradation.
The SENPl-RNF4 pathway has emerged as a crucial regulator of protein SUMOylation and de-SUMOylation. ZNF281 is a transcription factor that plays an important role in tumor cell proliferation, migration, and drug resistance. The study found that SENPl promotes ZNF281 SUMOylation, while RNF4 promotes the
degradation of SUMOylated ZNF281. The SENPl-RNF4 pathway regulates the stability and activity of ZNF281, which in turn affects tumor cell proliferation, migration, and drug resistance.
Through in vivo experiments using miRNA related to SENPl and RNF4, the study demonstrated that the proliferation of tumor cells was significantly reduced, and the tumor volume was significantly reduced after injection of these miRNAs. This indicates that the SENPl-RNF4 pathway may be a potential target for the prevention and treatment of colorectal cancer.
In conclusion, the SENPl-RNF4 pathway plays an important role in regulating ZNF281 SUMOylation and degradation, which affects tumor cell proliferation, migration, and drug resistance. Targeting this pathway may provide a new therapeutic strategy for colorectal cancer
It is important to note that while the SENPl-RNF4 pathway shows promise as a therapeutic target for colorectal cancer, further research is needed to fully understand its role in cancer development and progression. Additionally, the development of targeted therapies for this pathway will require careful consideration of potential off-target effects and the
use of appropriate animal models for preclinical testing.
Future studies may also focus on identifying other factors that regulate ZNF281 SUMOylation and degradation. For example, it is possible that other miRNAs or proteins may also play a role in this process. Identifying these additional factors could lead to the development of more effective targeted therapies for colorectal cancer.
In summary, the discovery of the SENPl-RNF4 pathway and its role in regulating ZNF281 SUMOylation and degradation represents an exciting new avenue for the development of targeted therapies for colorectal cancer. Continued research in this field will be essential for identifying new therapeutic targets and improving the outlook for patients with this disease
There is no doubt that colorectal cancer is a significant health concern worldwide, and new targeted therapies are urgently needed to improve patient outcomes. The discovery of the SENPl-RNF4 pathway represents a promising new avenue for developing such therapies, as it provides insights into the regulation of ZNF281 SUMOylation and degradation, which are crucial processes in the development and progression
of colorectal cancer.
However, it is clear that there is still much to be learned about the underlying mechanisms of colorectal cancer and the many factors that contribute to its development and progression. Future research in this field will undoubtedly focus on identifying new therapeutic targets and developing more effective treatment options for patients.
One area of particular interest is the emerging field of precision medicine, which aims to tailor treatments to individual patients based on their unique genetic profiles and other factors. By identifying the
specific molecular pathways involved in colorectal cancer and other types of cancer, researchers may be able to develop personalized treatments that are more targeted and effective than current treatments.
Another important area of research is the development of new diagnostic tools for colorectal cancer, which could enable earlier detection and more effective treatment of the disease. There is currently no definitive biomarker or screening test for colorectal cancer, and more research is needed to identify reliable biomarkers and develop more accurate and efficient screening methods.
In conclusion, the discovery of the SENPl-RNF4 pathway and its role in regulating ZNF281 SUMOylation and degradation represents an important step forward in the development of targeted therapies for colorectal cancer. However, there is still much to be learned about the underlying mechanisms of this disease, and further research is needed to identify new therapeutic targets and develop more effective treatments. By continuing to explore the complex biology of
colorectal cancer, we may be able to improve the outlook for millions of patients worldwide
In conclusion, dysregulation of ZNF281 SUMOylation and degradation plays a critical role in the development and progression of colorectal cancer. Targeting ZNF281 through SUMOylation and degradation pathways holds promise as a targeted therapy for this disease. However, further research is needed to advance our understanding of colorectal cancer biology and
identify new therapeutic targets to improve patient outcomes。