The paired-like homeodomain transcription factor 2 (PITX2) gene encodes a transcription factor controlled by the WNT/Dvl/CTNNB1 and Hedgehog/TGFB pathways in the pathogenesis of colorectal cancer (CRC).
The results showed that the expression of miR-34a was downregulated whereas TGF-β1 and VEGF were upregulated in CRC tumor tissues and peripheral blood macrophages.
The results of the current study revealed that miR‑329 suppresses CRC cell proliferation and invasion through targeting TGF‑β1, thus suggesting that targeting miR‑329/TGF‑β1 may provide a novel effective therapeutic approach for the treatment of patients with CRC.
In this study, we simultaneously investigated the protein expression pattern of 3 regulators in the TGF-β/SMAD signaling pathway, including SMAD4, PPM1A, and TGF-β1, and their clinicopathological correlations in CRCs by immunohistochemistry.
We identified three pathogenic mutations, p.R286X (g.8330C>T), p.W325C (g.8449G>T) and p.C373S (g.8592G>C), amongst the CRC cases which were not observed in 524 healthy controls. p.R286X localizes to the N-terminal of the TGF-β1 prodomain truncating the protein prior to the active domain. p.W325C and p.C373S mutations are predicted from protein homology modelling with BMP2 to impact deleteriously on BMP4 function.
However, C allele of TGF-β1 -509 C > T and A allele of -800 G > A were associated with increased risk of colorectal cancer (CRC), and OR (95%CI) was 1.23 (0.99-1.52) for CC vs. TT for -509 C > T and 6.64 (3.46-12.72) for A carriers vs. GG.
Recently, a transforming growth factor beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in colorectal carcinomas showing instability.
Transforming growth factor-beta1 (TGF-beta1) is overexpressed in a variety of malignant epithelial tumors and was suggested to be a marker of colorectal cancer.
We evaluated the TGF-β1 response and the expression of target genes including matrix metalloproteinases (MMPs) and plasminogen activator inhibitor (PAI)-1 of various epithelial CRC cell lines and primary CAFs in vitro.