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Updated: Feb 4, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
miR-3148 Is a Novel Onco-microRNA that Potentiates Tumor Growth In Vivo
Takaki Akamine1,2, Yosuke Morodomi1,2, Yui Harada2
1Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Background/Aim:
Alterations of microRNA expression in three-dimensional spheroids were examined to identify novel microRNAs that might be associated with tumorigenesis.
Materials And Methods:
Using microRNA microarray analysis, we screened for microRNAs that were dramatically up-regulated inside three-dimensional spheroids in genetically-modified HCT116 human colon cancer cells expressing Copepoda Green Fluorescent Protein under hypoxia.
Results:
miR-3148 was identified as a possible candidate onco-microRNA. A growth advantage of HCT116 cells stably expressing miR-3148 (HCT116-miR3148) was observed compared to parental cells in vivo, but not in vitro. Additionally, no change in growth under hypoxic or starvation conditions was seen in these cells cultured two-dimensionally; however, HCT116-miR3148 cells maintained as three-dimensional spheroids were highly resistant to hypoxic conditions. HCT116-miR3148 cells were more sensitive to mitogen-activated protein kinase (MAPK) kinase inhibitors and extracellular signal-regulated kinase (ERK) inhibitors.
Conclusion:
MiR-3148 may be a novel onco-microRNA that protects cancer cells from serious stress conditions through the MAPK/ERK pathway, especially in vivo.
Insights
MicroRNA-3148 (miR-3148) promotes colon cancer cell survival under stress conditions, particularly in vivo. This novel onco-microRNA may offer a new therapeutic target for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Investigating microRNA (miRNA) expression in three-dimensional (3D) spheroids is crucial for identifying novel tumorigenesis markers.
- Colon cancer cell behavior in 3D models can differ significantly from 2D cultures.
Purpose of the Study:
- To identify novel microRNAs associated with tumorigenesis by examining miRNA expression in 3D spheroids.
- To characterize the role of candidate onco-microRNAs in colon cancer progression.
Main Methods:
- MicroRNA microarray analysis was performed on genetically-modified HCT116 human colon cancer cells cultured as 3D spheroids under hypoxic conditions.
- Cell growth, stress resistance, and drug sensitivity were assessed in vitro and in vivo for cells engineered to express miR-3148.
Main Results:
- miR-3148 was identified as a significantly upregulated miRNA in 3D spheroids.
- HCT116 cells overexpressing miR-3148 exhibited enhanced growth in vivo but not in vitro.
- miR-3148 conferred resistance to hypoxia in 3D spheroids and increased sensitivity to MAPK/ERK pathway inhibitors.
Conclusions:
- miR-3148 functions as a novel onco-microRNA, protecting cancer cells from stress, especially in vivo.
- The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway is implicated in miR-3148's protective role.
- Targeting miR-3148 or the MAPK/ERK pathway may represent a therapeutic strategy for colon cancer.
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