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Updated: May 20, 2026

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
Published on: July 6, 2017
MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells
Zhigang Wang1, Xiaoping Zhang, Zhili Yang
1Department of General Surgery, Shanghai Jiaotong University Affiliated 6th People's Hospital, Shanghai, PR China.
Abstract:
MicroRNAs (miRNAs) are regulators of numerous cellular events; accumulating evidence indicates that miRNAs play a key role in a wide range of biological functions, such as cellular proliferation, differentiation, and apoptosis in cancer. Down-regulated expression of miR-145 has been reported in colon cancer tissues and cell lines. The molecular mechanisms underlying miR-145 and the regulation of colon carcinogenesis remain unclear. In this study, we investigated the levels of miR-145 in human colon cancer cells using qRT-PCR and found markedly decreased levels compared to normal epithelial cells. We identified PAK4 as a novel target of miR-145 using informatics screening. Additionally, we demonstrated that miR-145 targets a putative binding site in the 3'UTR of PAK4 and that its abundance is inversely associated with miR-145 expression in colon cancer cells; we confirmed this relationship using the luciferase reporter assay. Furthermore, restoration of miR-145 by mimics in SW620 cells significantly attenuated cell growth in vitro, in accordance with the inhibitory effects induced by siRNA mediated knockdown of PAK4. Taken together, these findings demonstrate that miR-145 downregulates P-ERK expression by targeting PAK4 and leads to inhibition of tumor growth.
Insights
MicroRNA-145 (miR-145) is downregulated in colon cancer. Restoring miR-145 inhibits tumor growth by targeting PAK4, a key regulator of cell proliferation.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) regulate cellular processes including proliferation, differentiation, and apoptosis in cancer.
- Downregulated microRNA-145 (miR-145) expression is observed in colon cancer, but its regulatory mechanisms remain unclear.
Purpose of the Study:
- To investigate the role of miR-145 in colon carcinogenesis.
- To identify novel targets of miR-145 and elucidate its mechanism of action in colon cancer cells.
Main Methods:
- Quantitative reverse transcription PCR (qRT-PCR) to measure miR-145 levels.
- Bioinformatic screening and luciferase reporter assays to identify and validate miR-145 targets.
- In vitro cell growth assays using miR-145 mimics and siRNA-mediated knockdown of PAK4.
Main Results:
- miR-145 levels were significantly decreased in human colon cancer cells compared to normal cells.
- PAK4 was identified as a direct target of miR-145, with an inverse correlation between their expression levels.
- Restoration of miR-145 suppressed colon cancer cell proliferation in vitro, mimicking the effects of PAK4 knockdown.
Conclusions:
- miR-145 acts as a tumor suppressor in colon cancer by targeting PAK4.
- miR-145 downregulates P-ERK signaling through PAK4, thereby inhibiting tumor growth.
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