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MiR-144 inhibits growth and metastasis in colon cancer by down-regulating SMAD4
Shihou Sheng1, Lin Xie2, Yuanyu Wu1
1Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China.
Abstract:
MicroRNAs (MiRs) are thought to display regulator action in tumor suppression and oncogenesis. miR-144 plays an important role in the development of various cancers, such as colorectal cancer, breast cancer, and lung cancer, by targetting different molecules potentially involved in many signaling pathways. SMAD4 is a common signaling during tumor progression, and it can inhibit cell proliferation and promote cell motility in most epithelial cells. The present study focused on the effect of miR-144 and SMAD4 on colon cancer in order to find the novel gene therapy target for the treatment of colon cancer. Quantitative real-time polymerase chain reaction was used to assess the expression level of miR-144 in colon cancer tissues and SW620 cells. MTT assay, scratch test, and transwell assay were used to evaluate cell proliferation, migration, and invasion, respectively. Moreover, luciferase assays were utilized to identify the predictive effect of miR-144 on SMAD4. Western blotting was performed to determine the relative expression of protein related to SMAD4. We found miR-144 level was significantly lower in colon cancer tissues and SW620 cells. Moreover, SMAD4 level, both in mRNA and protein, was obviously elevated in colon cancer tissues. Further, miR-144 mimics treatment inhibited cells proliferation, invasion, and migration. Fluorescence intensity of miR-144 mimics group in wild type cells was decreased. MiR-144 mimics repressed the SMAD4 expression both in mRNA and protein. These findings about miR-144/SMAD4 pair provide a novel therapeutic method for colon cancer patients.
Insights
MicroRNA-144 (miR-144) is downregulated in colon cancer, while SMAD4 is upregulated. Restoring miR-144 inhibits cancer cell growth and migration by repressing SMAD4, offering a potential gene therapy target.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- MicroRNAs regulate tumor suppression and oncogenesis.
- miR-144 is implicated in various cancers, including colorectal cancer.
- SMAD4 is a key signaling molecule in tumor progression.
Purpose of the Study:
- To investigate the role of miR-144 and SMAD4 in colon cancer.
- To explore the miR-144/SMAD4 interaction as a potential therapeutic target.
Main Methods:
- Quantitative real-time PCR to measure miR-144 and SMAD4 expression.
- MTT, scratch, and Transwell assays for cell proliferation, migration, and invasion.
- Luciferase and Western blot assays to validate miR-144 targeting of SMAD4.
Main Results:
- miR-144 expression was significantly lower in colon cancer tissues and cells.
- SMAD4 mRNA and protein levels were elevated in colon cancer tissues.
- miR-144 mimics suppressed colon cancer cell proliferation, invasion, and migration.
- miR-144 directly targeted and repressed SMAD4 expression.
Conclusions:
- The miR-144/SMAD4 pathway is dysregulated in colon cancer.
- Restoring miR-144 shows therapeutic potential for colon cancer treatment.
- The miR-144/SMAD4 interaction represents a novel therapeutic strategy.
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