Besides, luciferase reporter gene assay revealed that overexpression of miR-34a significantly attenuated the luciferase activity of the wild-type HOTAIR vector group without attenuating the mutant HOTAIR vector group (p>0.05) In addition, the recovery experiment also found a mutual regulation between HOTAIR and miR-34a, together they could affect the malignant progression of colon cancer.
We determined the expression and localization of PAI1 in 61 human primary colon cancers and compared them to MIR34A methylation and inactivating mutations in TP53.
In short, the current study suggests XIST plays as an important role in colon cancer progression targeted by miR-34a via Wnt/β-catenin signaling pathway, providing a novel insight for the pathogenesis and underlying therapeutic target for colon cancer.
<i>In vitro</i> miRNA functional assays demonstrated that miR-34a bound to the putative 3'-untranslated regions of Notch1 and Jagged1 in SW480 cells, and thereby attenuated the migration and invasion of the colon cancer cells.
rs35301225 in miR-34a was highly associated with a decreased risk of CRC in a Chinese population and might serve as a novel biomarker for colon cancer.
In this study, we investigated the role of ECSB in suppressing the growth of human colon cancer HCT‑8 cells, and whether this is mediated by regulation of miR‑34a and its downstream target genes, using real-time PCR and western blot analysis.
Our results demonstrated that HNF1A-AS1 mediated the metastatic progression of colon cancer in part through miR-34a/p53 signaling axis, and established its candidacy as a new prognostic biomarker and a potential novel therapeutic target.
Ectopic expression of miR-34a-5p in p53 wild-type colon cancer cell HCT116 significantly inhibited cell growth, migration, invasion and metastasis. miR-34a-5p induced cell apoptosis, cell cycle arrest at G1 phase and p53 transcription activity in HCT116 cells, but not in the HCT116 p53 knockout (p53(-/-)) cells. miR-34a-5p significantly suppressed the HCT116 growth in vivo, whereas it showed no effect on the HCT116 p53(-/-) xenograft, indicating that the growth-inhibiting effect by miR-34a-5p was dependent on p53.
Detection of miR-34a silencing in resected primary colon cancer may be of prognostic value, especially in combination with detection of c-Met and β-catenin expression.
The loss of expression of miR-34 in colon cancer is in part due to promoter hypermethylation of miR-34, which can be re-expressed with our novel agent CDF, suggesting that CDF could be a novel demethylating agent for restoring the expression of miR-34 family, and thus CDF could become a newer therapeutic agent for the treatment of colon cancer.
Unexpectedly, the DNA-binding activity of p53 was not inversely correlated with Fra-1 expression, and a significant statistical inverse correlation between miR-34a and Fra-1 expression was only observed in 14 of 40 (35%) colon cancer tissues.