Yuzhen Zhu

Ginsenoside Rh2 alleviates dextran sulfate sodium-induced colitis via augmenting TGFβ signaling

Ginsenoside Rh2 (GRh2) has been reported to have therapeutic effects on various diseases. However, whether it may also affect the recovery from ulcerative colitis remains unknown. Here we induced colitis in mice by dextran sulfate sodium (DSS) administration, and then treated the mice with GRh2. We found that GRh2-treated mice showed significant alleviation of the DSS-induced colitis. Moreover, significant increase in the activity of TGFβ signaling was detected in the GRh2-treated colon that had received DSS. To investigate whether there is a causative link among GRh2 treatment, TGFβ signaling augment and the cure of colitis, we gave the DSS-treated mice a combination of GRh2 and a specific TGFβ receptor I inhibitor, SB431542. SB431542 significantly decreased the activation of TGFβ signaling in the colon from the GRh2-administrated mice, and consequently attenuated the therapeutic effect of GRh2. Our data thus demonstrate that GRh2 may alleviate DSS-induced colitis via augmenting TGFβ signaling.

A critical role of mir-199a in the cell biological behaviors of colorectal cancer

BackgroundColorectal cancer (CRC) is one of the most common cancer and the leading causes of cancer mortality worldwide. The critical role of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) are important in the cancer development.MethodsThe purpose of this study was to investigate the association of miR-199a expression in CRC and non-tumor tissues as well as assessed the effect of miR-199a on biological behaviors including cell proliferation, apoptosis, migration and invasion of CRC cells. The expression of miR-199a was distinctly decreased in colorectal cancer tissues compared with non-neoplastic colorectal tissues.ResultsIn this study, we found that miR-199a down-regulation was associated with the CRC and metastasis incidence. Advanced study showed that miR-199a up-regulation would lead to decreased CRC proliferation, migration and invasion. However, no significant association of miR-199a treatment and apoptosis rate and cell-cycle were detected in this study. The detection for the mechanisms of miR-199a on the development of CRC showed that the anticarcinogenic effect of miR-199a might be produced through HIF-1α/VEGF pathway.ConclusionIt was found that miR-199a would reduce the proliferation, migration and invasion. However, overexpression of miR-199a on the apoptosis rate and cell cycles showed no significant results. The potential functionary mechanism of miR-199a might through HIF-1α/VEGF pathway.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9806714131513041.

Growth inhibition effects of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid on colorectal carcinoma cells and colon carcinoma-bearing mice

The aim of the present study was to investigate the mechanism underlying the antitumor effects of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) in colorectal cancer (CRC). 5F was isolated and used to treat C26 murine colon carcinoma cells, a xenograft tumor mouse model (induced by C26 cells) and a CRC mouse model [induced by 1,2-dimethylhydrazine (DMH)/dextran sodium sulfate (DSS)]. C26 cell growth was inhibited by 5F in a dose- and time-dependent manner in vitro. In addition, 5F induced cell apoptosis and cell cycle arrest in the G2 phase, increased the activity of caspase-3 and caspase-9, but did not affect the activity of cascase‑8, suggesting that 5F induced apoptosis via activation of the mitochondrial signaling pathway rather than the death‑receptor signaling pathway. Furthermore, treatment of C26 cells with 5F resulted in upregulation of cyclin‑dependent kinase inhibitor 1A (p21, Cip1), Bcl‑2‑associated X protein, nuclear factor of κ light polypeptide gene enhancer in B‑cells inhibitor, α and downregulation of B‑cell lymphoma 2, nuclear factor κ‑light‑chain enhancer of activated B cells and survivin. In vivo animal models demonstrated that 5F treatment protected mice from carcinogenesis induced by DMH/DSS and markedly decreased the xenograft tumor weight with minimal side effects. Therefore, 5F may have potential as an anti-CRC therapeutic agent for use in the clinical setting.

MiR-4500 is epigenetically downregulated in colorectal cancer and functions as a novel tumor suppressor by regulating HMGA2

ABSTRACT This study aimed to understand the exact function and potential mechanism of miR-4500 in colorectal cancer (CRC). In this study, the expression of miR-4500 was decreased in both CRC cells and tissues, and downregulated miR-4500 indicated advanced tumor stage and poor survival. By bisulfite sequencing analysis, we found that the CpG island in the promoter region of miR-4500 was hypermethylated in CRC cells and tissues compared with normal control cells and non-tumor tissues, respectively. Functionally, gain- and loss-of-function analyses indicated the tumor suppressor role of miR-4500: it suppressed cell proliferation, cell cycle progression, migration, and invasion. Predictive algorithms and experimental analyses identified HMGA2 as a direct target of miR-4500. Reintroducing HMGA2 impaired the inhibitory effects of miR-4500 on cell growth and motility. Clinically, higher HMGA2 protein expression in CRC tissues was associated with advanced tumor stage and poor survival. An inverse correlation was found between miR-4500 levels and HMGA2 protein expression. Taken together, this study provides the first evidence that miR-4500 functions as a novel tumor suppressor in the miR-4500/HMGA2 axis in colorectal carcinogenesis, and restoring miR-4500 expression might represent a promising therapeutic strategy for CRC.