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miR-142-3p Suppresses Cell Growth by Targeting CDK4 in Colorectal Cancer
Xiangyu Zhu1, Si-Ping Ma1, Dongxiang Yang2
1Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, Liaoning, China.
Background/Aims:
Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including colorectal cancer (CRC). Here, we investigated anomalous miR-142-3p expression and its possible functional consequences in primary CRC samples.
Methods:
The expression of miR-142-3p was measured by quantitative RT-PCR in 116 primary CRC tissues and adjacent non-tumor tissues. The effect of miR-142-3p up- or down-regulation in CRC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice.
Results:
Using quantitative RT-PCR, we found that miR-142-3p was down-regulated in 78.4 % (91/116) of the primary CRC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-142-3p mimic reduced in vitro cell viability and colony formation by inducing cell cycle arrest in CRC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-142-3p inhibitor increased the viability and colony forming capacity of CRC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-142-3p by predictions and dual-luciferase reporter assays. Concordantly, we found that miR-142-3p mimics and inhibitors could decrease and increase CDK4 protein levels in CRC-derived cells, respectively.
Conclusion:
From our results we conclude that miR-142-3p may act as a tumor suppressor in CRC and may serve as a tool for miRNA-based CRC therapy.
Insights
MicroRNA-142-3p (miR-142-3p) is frequently downregulated in colorectal cancer (CRC). Restoring miR-142-3p suppresses CRC cell growth and tumor development, indicating its tumor-suppressive role.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) deregulation is implicated in various cancers, including colorectal cancer (CRC).
- Investigating specific miRNA expression patterns, like miR-142-3p, is crucial for understanding CRC pathogenesis.
Purpose of the Study:
- To investigate the expression of miR-142-3p in primary colorectal cancer (CRC) tissues.
- To elucidate the functional role and molecular targets of miR-142-3p in CRC progression.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to assess miR-142-3p expression in 116 CRC tissues and adjacent non-tumor tissues.
- In vitro assays (cell viability, colony formation) and in vivo xenograft mouse models to evaluate the functional impact of miR-142-3p modulation.
- Dual-luciferase reporter assays to identify and validate potential molecular targets of miR-142-3p.
Main Results:
- miR-142-3p was significantly downregulated in 78.4% of primary CRC tissues compared to non-tumor controls.
- Upregulation of miR-142-3p using mimics suppressed CRC cell viability, colony formation, and in vivo tumor growth by inducing cell cycle arrest.
- Inhibition of miR-142-3p enhanced CRC cell proliferation and tumor growth.
- CDK4 was identified as a direct target of miR-142-3p, with its protein levels inversely correlated with miR-142-3p expression.
Conclusions:
- miR-142-3p functions as a tumor suppressor in colorectal cancer.
- Restoring miR-142-3p expression holds potential as a therapeutic strategy for CRC.
- Targeting miR-142-3p and its downstream effectors like CDK4 may offer novel avenues for CRC treatment.
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