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DNA methylation-regulated and tumor-suppressive roles of miR-487b in colorectal cancer via targeting MYC, SUZ12, and KRAS.
- Source :
-
Cancer medicine [Cancer Med] 2019 Apr; Vol. 8 (4), pp. 1694-1709. Date of Electronic Publication: 2019 Feb 21. - Publication Year :
- 2019
-
Abstract
- Human colorectal cancer (CRC), characterized by its high morbidity and lethality, seriously threatens human health and lives. MicroRNA-487b (miR-487b) is currently reported to be aberrantly expressed in several tumors, but the detailed functions and underlying mechanisms of miR-487b in CRC remain unclear. Here, we found that miR-487b is downregulated in CRC cell lines and is markedly decreased in tumor specimens derived from CRC patients. MiR-487b inhibits cell proliferation, migration and invasion and promotes the apoptosis of CRC cells in vitro. Statistical analysis of clinical samples indicates that miR-487b may serve as a biomarker for early CRC diagnosis. Inverse correlations between the expression levels of MYC, SUZ12, and KRAS and that of miR-487b exist in vitro and in CRC patient tissue specimens. Further experiments demonstrated the regulatory effects of miR-487b on MYC, SUZ12, and KRAS, and the disruption of these genes partially restores the miR-487b inhibitor-induced phenotype. Additionally, miR-487b promoter region is in a DNA hypermethylated condition and the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-Aza) increases the levels of miR-487b but suppresses the expression of MYC, SUZ12, and KRAS in a time- and concentration-dependent manner in CRC cells. Collectively, miR-487b is regulated by DNA methylation and it functions as a tumor suppressor in CRC mainly through targeting MYC, SUZ12, and KRAS. Our study provides insight into the regulatory network in CRC cells, offering a new target for treating CRC patients.<br /> (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Subjects :
- Cell Line, Tumor
Cell Movement genetics
Cell Proliferation genetics
Epithelial-Mesenchymal Transition genetics
Humans
Models, Biological
Neoplasm Proteins
RNA Interference
Transcription Factors
Colorectal Neoplasms genetics
DNA Methylation
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Genes, myc
Polycomb Repressive Complex 2 genetics
Proto-Oncogene Proteins p21(ras) genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-7634
- Volume :
- 8
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer medicine
- Publication Type :
- Academic Journal
- Accession number :
- 30791232
- Full Text :
- https://doi.org/10.1002/cam4.2032