This article is the original of the Translational Medicine Network, **Please indicate the source
Author: Jerry
Reading guide:Tumor metastasis severely limits the prognosis of patients with gastric cancer. RNA-binding proteins (RBPs) play a crucial role in tumor metastasis, but there is limited research on their role in gastric cancer.
On December 19, the research team of Liu Weizhen and Tao Kaixiong from Huazhong University of Science and Technology published a study entitled "ESRP1-driven alternative splicing of clstn1 inhibits the metastasis of gastric cancer" in the journal Cell Death Discovery** In this study, the researchers found that RBP-specific ESRP1 in epithelial cells plays an important role in regulating the metastasis of gastric cancer cells. ESRP1 was inversely associated with distant metastasis and lymph node metastasis in gastric cancer patients. The researchers demonstrated in vitro and in vivo that ESRP1 inhibits the migration and invasion of gastric cancer. This study highlights the role of ESRP1 in the regulation of gastric cancer metastasis and expands its mechanism. These results provide the possibility for ESRP1 and CLSTN1 to become the most important targets for gastric cancer metastasis.
Background:
Gastric cancer is one of the most common malignancies, with more than 1 million cases per year, accounting for 5 percent of all cancer diagnoses6%。Gastric cancer is often diagnosed at an advanced stage due to its insidious onset and lack of specific clinical manifestations, accompanied by local, regional or distant metastases. Tumor metastasis is the main factor affecting the prognosis of gastric cancer, and the 5-year survival rate of early gastric cancer is as high as 70%, and the 5-year survival rate of advanced gastric cancer is less than 30%. Therefore, screening targets associated with gastric cancer metastasis, their functions and underlying mechanisms, can help improve the prognosis and prognosis of gastric cancer patients.
RNA-binding proteins (RBPS) are an evolutionarily highly conserved class of proteins that have an RNA-binding domain that enables them to interact with RNA. RBPs account for about 10% of all protein-coding genes. They are involved in the alternative splicing regulation, transport, and localization of mRNAs, and play an important role in maintaining genome diversity and stability. Studies have shown that RBPs are closely related to tumorigenesis and development, and can affect tumor cell proliferation and epithelial-mesenchymal transition (EMT) by regulating pre-mRNA alternative splicing.
Research Progress
In order to further verify the effect of ESRP1 on gastric cancer metastasis, the researchers constructed two ESRP1-overexpressing gastric cancer cell lines based on SGC7901 and BGC823, which had low endogenous ESRP1 expression levels. Invasion experiments showed that the migration and invasion ability of gastric cancer cells decreased after overexpression of ESRP1. Ecadherin and ncadherin are two important indicators of epithelial-mesenchymal transition (EMT). The researchers also found that after gastric cancer cells overexpressed ESRP1, the expression of ecadherin increased and the expression of ncadherin decreased, suggesting that ESRP1 may inhibit the EMT process. The researchers then verified the function of ESRP1 in vivo through tail vein injection experiments in mice. The results showed that the number of pulmonary metastases nodules in the ESRP1 overexpression group was significantly lower than that in the control group. The results of lung immunohistochemistry in mice showed that the expression of ecadherin in lung metastases in the ESRP1 overexpression group was significantly increased.
In vitro and in vivo studies have shown that overexpression of ESRP1 inhibits the migration and invasion of gastric cancer.
After ESRP1 knockdown, AGS cells and MKN45 cells showed increased migration and invasion, decreased Ecadherin expression and increased Ncadherin expression in invasion experiments, suggesting that cells may undergo interstitial metastasis, which was further confirmed by the increase in lung metastases in mice injected with MKN45 ShesrP1 cells, and the decrease in Ecadherin protein levels in metastases. These results suggest that ESRP1 inhibits the metastasis of gastric cancer cells.
To study the role of CLSTN1 in gastric cancer metastasis, the researchers constructed full-length (CLSTN1-F) and truncated (CLSTN1-S) overexpression plasmids. Through invasion experiments, the researchers found that overexpression of truncated CLSTN1 (CLSTN1-S) significantly reduced the migration and invasion of gastric cancer cells, while overexpression of CLSTN1-F promoted the migration and invasion of gastric cancer cells. In addition, the researchers examined the effect of ClstN1 on key EMT proteins and found that ClstN1-S promoted Ecadherin protein expression and inhibited Ncadherin expression, while ClstN1-F did the opposite, suggesting that ClstN1-S may mediate ESRP1-induced inhibition of gastric cancer metastasis. These results suggest that CLSTN1-S plays a key role in mediating ESRP1 inhibition of gastric cancer cell metastasis.
CLSTN1 exon 11 splicing mediates ESRP1-induced inhibition of metastasis in gastric cancer cells.
Conclusions of the study
In summary, this study confirmed that ESRP1 expression and CLSTN1 splicing levels were negatively correlated with gastric cancer metastasis in vitro, in vivo, and clinical samples. This study provides new insights into the molecular regulation of ESRP1-CLSTN1 and its role in gastric cancer metastasis. An in-depth understanding of the molecular regulation of ESRP1-CLSTN1 will help to design** or prevent new strategies for gastric cancer metastasis.
References: Note: This article aims to introduce the progress of medical research and cannot be used as a reference for ** scheme. If you need health guidance, please visit a regular hospital.
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