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Updated: May 3, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA
Yihui Wang1, Qingchao Tang2, Mingqi Li1
1Department of Colorectal Surgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, 150081 Harbin, China.
Abstract:
Colorectal cancer (CRC) is the second most common cause of death from cancer. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by triggering RNA degradation or interfering with translation. Aberrant miRNA expression is involved in human disease including cancer. Herein, we showed that miR-375 was frequently down-regulated in human colorectal cancer cell lines and tissues when compared to normal human colon tissues. PIK3CA was identified as a potential miR-375 target by bioinformatics. Overexpression of miR-375 in SW480 and HCT15 cells reduced PIK3CA protein expression. Subsequently, using reporter constructs, we showed that the PIK3CA untranslated region (3'-UTR) carries the directly binding site of miR-375. Additionally, miR-375 suppressed CRC cell proliferation and colony formation and led to cell cycle arrest. Furthermore, miR-375 overexpression resulted in inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. SiRNA-mediated silencing of PIK3CA blocked the inhibitory effect of miR-375 on CRC cell growth. Lastly, we found overexpressed miR-375 effectively repressed tumor growth in xenograft animal experiments. Taken together, we propose that overexpression of miR-375 may provide a selective growth inhibition for CRC cells by targeting PI3K/Akt signaling pathway.
Insights
MicroRNA-375 (miR-375) is downregulated in colorectal cancer (CRC). Restoring miR-375 inhibits CRC cell growth and tumor progression by targeting PIK3CA and the PI3K/Akt pathway.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Colorectal cancer (CRC) is a leading cause of cancer-related mortality.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various cancers.
- Aberrant miRNA expression is a hallmark of human diseases, including cancer.
Purpose of the Study:
- To investigate the role of miR-375 in colorectal cancer.
- To identify targets of miR-375 and elucidate its mechanism of action in CRC.
Main Methods:
- Bioinformatic analysis to predict miR-375 targets.
- Cell culture experiments (SW480, HCT15) to assess miR-375 effects on cell proliferation, colony formation, and cell cycle.
- Reporter assays to confirm direct binding of miR-375 to PIK3CA 3'-UTR.
- Western blotting to analyze protein expression (PIK3CA, p-Akt).
- Xenograft mouse models to evaluate in vivo tumor growth inhibition.
Main Results:
- miR-375 was significantly downregulated in human CRC cell lines and tissues.
- PIK3CA was identified as a direct target of miR-375, with miR-375 binding to the PIK3CA 3'-UTR.
- Overexpression of miR-375 suppressed CRC cell proliferation, colony formation, and induced cell cycle arrest.
- miR-375 inhibited the PI3K/Akt signaling pathway.
- Silencing PIK3CA using siRNA abrogated the inhibitory effects of miR-375 on CRC cell growth.
- Overexpressed miR-375 repressed tumor growth in vivo.
Conclusions:
- miR-375 acts as a tumor suppressor in colorectal cancer.
- The tumor-suppressive function of miR-375 is mediated through the direct targeting of PIK3CA and subsequent inhibition of the PI3K/Akt signaling pathway.
- Restoration of miR-375 may represent a potential therapeutic strategy for colorectal cancer.
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