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Updated: Nov 2, 2025

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
MicroRNA‑142‑3p suppresses cell proliferation, invasion and epithelial‑to‑mesenchymal transition via RAC1‑ERK1/2
Na Xie1, Qiuping Meng2, Yixin Zhang1
1Department of Pathology, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, P.R. China.
Abstract:
Aberrant expression of microRNAs (miRNAs/miRs) is associated with the initiation and progression of colorectal cancer (CRC), but how they regulate colorectal tumorigenesis is still unknown. The present study was designed to investigate the expression profile of miRNAs in human CRC tissues, and to reveal the molecular mechanism of miRNA‑142‑3p in suppressing colon cancer cell proliferation. The expression of miRNA was examined using an Exiqon miRNA array. Bioinformatics was used to predict the target genes of differentially expressed miRNAs and to analyze their biological function in CRC. The effect of miR‑142‑3p in colon cancer cells was evaluated in vitro using cell proliferation, colony formation and Transwell assays. Dual‑luciferase reporter gene assays were performed to investigate the association between miR‑142‑3p and Rac family small GTPase 1 (RAC1). The effect of miR‑142‑3p regulation on colon cancer proliferation was assessed through western blotting and quantitative polymerase chain reaction analysis. Compared with their expression in adjacent non‑cancer mucosal tissues, 76 miRNAs were upregulated and 102 miRNAs were downregulated in CRC. One of the most significantly and differentially regulated miRNAs was miR‑142‑3p, which was downregulated in 81.0% (51/63) of primary CRC tissues. After transfection of miR‑142‑3p mimics into colon cancer cells, proliferation and colony formation were decreased, and migration and invasion were markedly suppressed. RAC1 was a possible target of miR‑142‑3p, which was confirmed by dual‑luciferase reporter assay. Transfection of miR‑142‑3p mimics decreased the levels of RAC1 and suppressed epithelial‑to‑mesenchymal transition in colon cancer cells. The phosphorylation of extraceullar signal‑regulated kinase (ERK) was decreased significantly by the inhibition of RAC1 or transfection of miR‑142‑3p mimics in colon cancer cells. In conclusion, aberrant miRNAs are implicated in CRC. Decreased expression of miR‑142‑3p may be associated with CRC tumorigenesis via Rac1‑ERK signaling.
Insights
Decreased microRNA-142-3p (miR-142-3p) expression is linked to colorectal cancer (CRC) development. This study reveals miR-142-3p suppresses colon cancer proliferation by targeting RAC1, impacting the RAC1-ERK signaling pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aberrant microRNA (miRNA) expression is implicated in colorectal cancer (CRC) initiation and progression.
- The precise regulatory roles of miRNAs in colorectal tumorigenesis remain largely undefined.
Purpose of the Study:
- To investigate the miRNA expression profile in human CRC tissues.
- To elucidate the molecular mechanism by which miRNA-142-3p (miR-142-3p) suppresses colon cancer cell proliferation.
Main Methods:
- miRNA expression profiling using Exiqon miRNA array.
- Bioinformatic analysis for target gene prediction and functional analysis.
- In vitro assays (proliferation, colony formation, Transwell) to assess miR-142-3p effects.
- Dual-luciferase reporter assays to confirm miR-142-3p targeting of RAC1.
- Western blotting and qRT-PCR to analyze protein and gene expression levels.
Main Results:
- 76 miRNAs were upregulated and 102 downregulated in CRC tissues compared to adjacent non-cancerous tissues.
- miR-142-3p was significantly downregulated in 81% of primary CRC tissues.
- miR-142-3p mimics suppressed colon cancer cell proliferation, migration, and invasion.
- RAC1 was identified as a direct target of miR-142-3p, and its levels were reduced by miR-142-3p mimics.
- miR-142-3p and RAC1 inhibition decreased ERK phosphorylation, suppressing epithelial-to-mesenchymal transition.
Conclusions:
- Aberrant miRNA expression is a key feature of colorectal cancer.
- Downregulation of miR-142-3p may contribute to CRC tumorigenesis.
- The miR-142-3p/RAC1/ERK signaling pathway represents a potential therapeutic target for colorectal cancer.
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