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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
miR-141 promotes colon cancer cell proliferation by inhibiting MAP2K4
Lei Ding1, Li-Li Yu1, Ning Han1
1Department of Radiology, The Third Hospital of Jilin University, Changchun, Jilin 130000, P.R. China.
Abstract:
MicroRNAs (miRNAs or miRs) can function as tumor-suppressor or oncogenic genes. Upregulation of miRNA-141 has been frequently observed in colorectal cancer (CRC) samples. The experimentally observed targets of miR-141 include the tumor-suppressor gene mitogen-activated protein kinase kinase 4 (MAP2K4). The aim of the present study was to investigate the role of miR-141 in the proliferation of colonic cancer. Western blotting, immunohistochemistry and reverse transcription-quantitative polymerase chain reaction were used to detect the expression levels of miR-141 and MAP2K4 in colonic adenocarcinoma (CAC) and adjacent non-cancerous (NC) tissue samples, as well as in human CAC cell lines (HT29, T94 and LS174). MTT assay was used to investigate the proliferation and apoptosis of these three cell lines. The expression levels of miR-141 were significantly upregulated in clinical samples of CAC, compared with adjacent NC tissues. By contrast, MAP2K4 was downregulated in CAC. The in vitro assays demonstrated that overexpression of miR-141 resulted in cell proliferation of CAC by inhibiting MAP2K4 activity. Our study suggests that targeting the miR-141-MAP2K4 signaling pathway may represent a novel approach for the treatment of CRC.
Insights
MicroRNA-141 (miR-141) is upregulated in colorectal cancer (CRC), inhibiting the tumor suppressor MAP2K4 and promoting cancer cell proliferation. Targeting this miR-141-MAP2K4 pathway offers a potential new CRC treatment strategy.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) play dual roles as tumor suppressors or oncogenes.
- Increased miRNA-141 (miR-141) expression is frequently observed in colorectal cancer (CRC).
- Mitogen-activated protein kinase kinase 4 (MAP2K4) is a known tumor suppressor and a target of miR-141.
Purpose of the Study:
- To investigate the role of miR-141 in the proliferation of colonic cancer.
- To examine the relationship between miR-141 and MAP2K4 expression in colorectal adenocarcinoma (CAC).
Main Methods:
- Western blotting and immunohistochemistry to assess protein expression.
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for gene expression analysis.
- MTT assays to evaluate cell proliferation and apoptosis in CAC cell lines.
Main Results:
- miR-141 was significantly upregulated in CAC tissues compared to adjacent non-cancerous (NC) tissues.
- MAP2K4 expression was downregulated in CAC tissues.
- Overexpression of miR-141 in vitro inhibited MAP2K4 activity, leading to increased CAC cell proliferation.
Conclusions:
- miR-141 promotes colonic cancer cell proliferation by suppressing MAP2K4.
- The miR-141-MAP2K4 signaling pathway is a potential therapeutic target for CRC treatment.
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