Downregulation of microRNA‑629‑5p in colorectal cancer and prevention of the malignant phenotype by direct targeting of low‑density lipoprotein receptor‑related protein 6

  • Authors:
    • Guoqiang Yan
    • Chenyao Li
    • Yuhang Zhao
    • Meng Yue
    • Lei Wang
  • View Affiliations

  • Published online on: June 18, 2019     https://doi.org/10.3892/ijmm.2019.4245
  • Pages: 1139-1150
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Abstract

Aberrant expression of numerous microRNAs (miRNAs/miRs) in colorectal cancer (CRC) significantly affects disease progression. Recently, miR‑629‑5p (miR‑629) was identified as a tumor‑promoting miRNA in the malignant processes of a number of human cancers. However, few studies have been conducted regarding expression profiles and detailed roles of miR‑629 in CRC. In the present study, reverse transcription‑quantitative polymerase chain reaction was used to assess miR‑629 expression in CRC tissues and cell lines. Cell Counting Kit‑8 assay, flow cytometry and Transwell assays were performed to determine the in vitro effects of miR‑629 on CRC cell proliferation, apoptosis, and metastasis, respectively. Xenograft models were employed to determine the in vivo effects of miR‑629 on tumor growth in nude mice. Molecular mechanisms underlying the activity of miR‑629 in CRC cells were explored. miR‑629 expression decreased in CRC tissues and cell lines. The decreased aberrant miR‑629 expression was significantly associated with tumor size, lymphatic metastasis and tumor‑node‑metastasis stage of CRC, and was a predictor of poor prognosis. Restoring miR‑629 expression attenuated CRC cell proliferation, migration and invasion; promoted cell apoptosis in vitro; and inhibited tumor growth in vivo. Low‑density lipoprotein receptor‑related protein 6 (LRP6) was a direct target gene of miR‑629 in CRC cells. Furthermore, the effect of LRP6 knockdown was similar to that of miR‑629 overexpression in CRC cells. Restoration of LRP6 expression neutralized the effects of miR‑629 in CRC cells. miR‑629 suppressed the activation of the Wnt/β‑catenin pathway through LRP6 regulation both in vitro and in vivo. In conclusion, miR‑629 suppressed the development and progression of CRC by directly targeting LRP6 and inhibiting the Wnt/β‑catenin pathway both in vitro and in vivo. Therefore, miR‑629 may be a novel prognostic biomarker and therapeutic target in CRC.

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September 2019
Volume 44 Issue 3

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APA
Yan, G., Li, C., Zhao, Y., Yue, M., & Wang, L. (2019). Downregulation of microRNA‑629‑5p in colorectal cancer and prevention of the malignant phenotype by direct targeting of low‑density lipoprotein receptor‑related protein 6. International Journal of Molecular Medicine, 44, 1139-1150. https://doi.org/10.3892/ijmm.2019.4245
MLA
Yan, G., Li, C., Zhao, Y., Yue, M., Wang, L."Downregulation of microRNA‑629‑5p in colorectal cancer and prevention of the malignant phenotype by direct targeting of low‑density lipoprotein receptor‑related protein 6". International Journal of Molecular Medicine 44.3 (2019): 1139-1150.
Chicago
Yan, G., Li, C., Zhao, Y., Yue, M., Wang, L."Downregulation of microRNA‑629‑5p in colorectal cancer and prevention of the malignant phenotype by direct targeting of low‑density lipoprotein receptor‑related protein 6". International Journal of Molecular Medicine 44, no. 3 (2019): 1139-1150. https://doi.org/10.3892/ijmm.2019.4245