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Published on: September 15, 2023
miR-452 promotes the development of gastric cancer via targeting EPB41L3
1Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei, China.
Abstract:
Gastric cancer is the most common malignant tumor of the digestive system and it is beneficial to find a safer and more effective therapeutic target if we have a deep understanding of the molecular function mechanism during the development of gastric cancer. In recent years, through many researches, we found that miRNA functions as oncogene or cancer suppressor gene, and it plays an important role in the occurrence and development of tumors. Many researches also showed that miR-452 has different expression patterns and roles in different tumors. Its expression is significantly reduced in glioma, breast cancer, colorectal cancer and prostate cancer; however, the expression is significantly increased in liver cancer, renal clear cell carcinoma, esophageal cancer and urothelial carcinoma, etc. However, the role and mechanism of miR-452 in gastric cancer is still unclear. In this study, we found that miR-452 was highly expressed in both tumor tissue and gastric cancer cells, and could directly target the cancer suppressor gene EPB41L3 3'-UTR. miR-452 significantly promoted the proliferation, migration and the S-phase arrest of gastric cancer cells, but EPB41L3 as a downstream target gene of miR-452 reversed such promoting effect. While down-regulation of miR-452 expression significantly inhibited the malignant biological behavior of gastric cancer cells, but this inhibitory effect was reversed by EPB41L3 siRNA. In addition, miR-452 in the gastric cancer xenograft model in nude mice could down-regulated the expression level of EPB41L3 and promote the growth of transplanted tumor in nude mice. Taken together, this study reveals the role of miR-452 in gastric cancer via inhibiting the target gene EPB41L3, suggesting that miR-452 has the potential to become a new target for the diagnosis and treatment of gastric cancer.
Insights
MicroRNA-452 (miR-452) promotes gastric cancer progression by suppressing the EPB41L3 tumor suppressor gene. This study identifies miR-452 as a potential diagnostic and therapeutic target for gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer is a prevalent digestive system malignancy.
- MicroRNAs (miRNAs) are key regulators in tumorigenesis, acting as oncogenes or tumor suppressors.
- The role of miR-452 in gastric cancer remains largely unelucidated, despite its varied expression in other cancers.
Purpose of the Study:
- To investigate the role and molecular mechanism of miR-452 in gastric cancer development.
- To identify potential therapeutic targets for gastric cancer based on molecular mechanisms.
Main Methods:
- Analysis of miR-452 expression in gastric cancer tissues and cells.
- Luciferase reporter assays to confirm direct targeting of EPB41L3 by miR-452.
- In vitro cell proliferation, migration, and cell cycle assays.
- In vivo xenograft mouse models to assess tumor growth.
- Manipulation of miR-452 and EPB41L3 expression using siRNA and overexpression techniques.
Main Results:
- miR-452 was significantly upregulated in gastric cancer tissues and cells.
- miR-452 directly targets the 3'-UTR of the tumor suppressor gene EPB41L3.
- Overexpression of miR-452 promoted gastric cancer cell proliferation and migration, and induced S-phase arrest.
- Downregulation of miR-452 inhibited malignant behaviors, an effect reversed by EPB41L3 knockdown.
- In vivo, miR-452 promoted tumor growth by downregulating EPB41L3.
Conclusions:
- miR-452 acts as an oncogene in gastric cancer by inhibiting the tumor suppressor EPB41L3.
- miR-452 promotes gastric cancer cell proliferation, migration, and tumor growth.
- miR-452 represents a potential novel diagnostic and therapeutic target for gastric cancer.
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