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miR-22 Suppresses EMT by Mediating Metabolic Reprogramming in Colorectal Cancer through Targeting MYC-Associated
Shusen Xia1,2,3, Xianyan Wang4, Yi Wu1,2
1The Second Department of General Surgery, The Affiliated Hospital of the North Sichuan Medical College, Nanchong, 637000 Sichuan, China.
Abstract:
Colorectal cancer (CRC) is one of the most frequent gastrointestinal cancers. MicroRNAs (miRNAs) have been proved to be unusually expressed in CRC progression and thus alter multiple pathological processes in CRC cells. However, the specific roles and mechanisms of miR-22 in CRC have not been clearly reported. MicroRNA-22 (miR-22) and MYC-associated factor X (MAX) expressions were determined by RT-qPCR in CRC tissues and cells. The targeted regulatory effects of miR-22 and MAX were confirmed by luciferase reporter and coimmunoprecipitation assays. Also, gain- and loss-of-function and rescue experiments were used to elucidate the function and mechanism of miR-22 and MAX in CRC cells and the mouse xenograft model. We discovered that miR-22 was hypermethylated and downregulated, while MAX was upregulated in CRC. miR-22 markedly inhibited migration, invasion, glycolysis, and cancer stem cell transcription factors in CRC cells. In addition, it was found that miR-22 can directly target MAX. Additional functional experiments confirmed that MAX overexpression can rescue the effects of miR-22 on the behavior of CRC cells. This study suggested that miR-22, as a cancer suppressor, participates in CRC progression by targeting MAX, which might provide basic information for therapeutic targets for CRC.
Insights
MicroRNA-22 (miR-22) acts as a tumor suppressor in colorectal cancer (CRC) by targeting MAX. Downregulation of miR-22 promotes CRC progression, offering potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancer (CRC) is a prevalent gastrointestinal malignancy.
- MicroRNAs (miRNAs) exhibit altered expression in CRC, influencing cellular processes.
- The specific role of microRNA-22 (miR-22) in CRC remains incompletely understood.
Purpose of the Study:
- To investigate the expression, function, and mechanism of miR-22 in colorectal cancer.
- To determine the relationship between miR-22 and MYC-associated factor X (MAX) in CRC.
- To explore the potential of miR-22 as a therapeutic target for CRC.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) for gene expression analysis.
- Luciferase reporter and coimmunoprecipitation assays for target validation.
- Gain- and loss-of-function studies in CRC cells and a mouse xenograft model.
Main Results:
- miR-22 was found to be hypermethylated and downregulated in CRC tissues and cells.
- MAX expression was upregulated in CRC.
- miR-22 inhibited CRC cell migration, invasion, glycolysis, and cancer stem cell transcription factors by directly targeting MAX.
Conclusions:
- miR-22 functions as a tumor suppressor in colorectal cancer.
- The miR-22/MAX axis plays a critical role in CRC progression.
- Targeting miR-22 may offer a novel therapeutic strategy for colorectal cancer.
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