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Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
MiR-181d inhibits cell proliferation and metastasis through PI3K/AKT pathway in gastric cancer
1General Surgery, Wuxi No. 4 People's Hospital, Affiliated Hospital of Jiangnan University, Wuxi, China. drraphaeljk@126.com.
Objective:
Gastric cancer is the second highest mortality tumor and the fourth most common cancer worldwide that has high aggressiveness. MicroRNA-181d (miR-181d) has been established to be a tumor suppressor, by suppressing cell proliferation, cell cycle, and promoting apoptosis in several cancers. The purpose of this study is to explore the great roles of miR-181d in gastric cancer.
Patients And Methods:
The Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot were applied to calculate the mRNA and protein levels of miR-181d and genes. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assays were utilized to measure the proliferative and invasive abilities. The Kaplan-Meier method was conducted to calculate the overall survival of gastric cancer patients.
Results:
MiR-181d was detected to be downregulated in gastric cancer tissues and cell lines compared to the peritumoral normal tissues and normal cell line. Downregulation of miR-181d predicted poor prognosis of gastric cancer patients. Cylindromatosis gene (CYLD) was overexpressed in gastric cancer tissues, which was confirmed to be a target gene of miR-181d in gastric cancer cell line HGC-27. Moreover, miR-181d inhibited the proliferation through CYLD/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway and inhibited the invasion-mediated epithelial-mesenchymal transition (EMT) in HGC-27 cells. In addition, overexpression of miR-181d suppressed tumor growth and xenograft tumorigenesis of HGC-27 cells in vivo.
Conclusions:
MiR-181d functioned as a tumor suppressor by inhibiting the proliferation via PI3K/AKT pathway in vitro and in vivo and inhibiting invasion-mediated epithelial-mesenchymal transition (EMT) by targeting CYLD in gastric cancer. The newly identified miR-181d/CYLD axis provides novel insight into the pathogenesis of gastric cancer.
Insights
MicroRNA-181d (miR-181d) acts as a tumor suppressor in gastric cancer, inhibiting proliferation and invasion. Its downregulation correlates with poor patient prognosis, highlighting its therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer is a leading cause of cancer mortality globally.
- MicroRNA-181d (miR-181d) is recognized as a tumor suppressor in various cancers.
- The specific role of miR-181d in gastric cancer requires further elucidation.
Purpose of the Study:
- To investigate the functional significance of miR-181d in gastric cancer.
- To determine the relationship between miR-181d expression and patient prognosis.
- To identify the molecular mechanisms underlying miR-181d's action in gastric cancer.
Main Methods:
- Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot for gene and protein expression analysis.
- MTT and Transwell assays to assess cell proliferation and invasion.
- Kaplan-Meier analysis for overall survival prediction.
- In vivo xenograft models to evaluate tumor growth suppression.
Main Results:
- miR-181d was significantly downregulated in gastric cancer tissues and cell lines.
- Lower miR-181d levels were associated with poor patient prognosis.
- miR-181d directly targeted Cylindromatosis gene (CYLD), inhibiting the CYLD/PI3K/AKT pathway and epithelial-mesenchymal transition (EMT).
- Overexpression of miR-181d suppressed tumor growth both in vitro and in vivo.
Conclusions:
- miR-181d functions as a tumor suppressor in gastric cancer by inhibiting proliferation and invasion.
- The miR-181d/CYLD axis plays a crucial role in gastric cancer pathogenesis.
- This study offers new insights into gastric cancer development and potential therapeutic strategies targeting the miR-181d/CYLD pathway.
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