Knockdown of metadherin inhibits cell proliferation and migration in colorectal cancer

Abstract

Metadherin (MTDH) is a multifunctional oncogene involved in tumor cell migration and metastasis through regulating a number of oncogenic signaling pathways in various human malignancies. Previous studies have demonstrated that MTDH is overexpressed in human colorectal cancer (CRC) and associated with cancer progression and a poor prognosis. However, the underlying mechanisms remain largely unknown. The present study investigated the expression and role of MTDH in CRC cells as well as the underlying mechanism of this. Western blot analysis and quantitative polymerase chain reaction were conducted to determine protein and mRNA expression of MTDH in three human CRC cell lines. A short hairpin RNA (shRNA) targeting MTDH was introduced into CRC HCT116 cells to stably inhibit MTDH expression. A Cell Counting Kit‑8 assay, colony formation assay, Transwell assay and flow cytometry were used to investigate the effect of MTDH‑knockdown on cell proliferation, migration, apoptosis and cell cycle arrest. Western blotting was performed to examine the protein expression levels of cell growth‑ and apoptosis‑associated genes. The results demonstrated that MTDH was commonly expressed in CRC cell lines. MTDH silencing significantly suppressed cell growth, colony forming ability and migration while inducing the apoptosis of HCT116 cells. In addition, MTDH depletion induced S phase cell cycle arrest in HCT116 cells. Mechanistically, knockdown of MTDH markedly downregulated the expression of phosphorylated protein kinase B, c‑Myc, proliferating cell nuclear antigen and B‑cell lymphoma 2 (Bcl‑2) protein in HCT116 cells, and the expression of p53 and Bcl‑2‑associated X protein was significantly increased compared with the negative control shRNA group (P<0.05), suggesting that MTDH may function through the expression of numerous types of apoptosis‑associated and signaling channel proteins in CRC cells. Taken together, these data indicated that MTDH may serve as a biomarker and candidate therapeutic target for CRC.

Nestin contributes to skeletal muscle homeostasis and regeneration

“…Firstly, nestin is known to be expressed in several rapidly expanding cells, such as in many progenitor cell types and in various cancers (Tampaki et al, 2014;Wiese et al, 2004). Secondly, nestin downregulation has been repeatedly shown to negatively affect the cell cycle and proliferation of many cell types (Daniel et al, 2008;Li et al, 2015;Tschaharganeh et al, 2014;Zhao et al, 2014). In light of these observations, it is highly plausible that the regenerative muscle phenotype and delayed muscle healing observed in the NesKO mice would be consequences of the decreased proliferation rate of the satellite cells.…”

“…et al, 2007). Furthermore, nestin expression has been correlated with proliferation in several non-myogenic cell models (Daniel et al, 2008;Li et al, 2015;Tschaharganeh et al, 2014;Zhao et al, 2014). Therefore, we found it relevant to study the behavior of NesKO muscle stem cells in more detail.…”

Knockdown of PKM2 and GLS1 expression can significantly reverse oxaliplatin-resistance in colorectal cancer cells

“…After its knockdown in the THC8307 cell line, all phenotype experiments were re-performed. All protocols were performed according to the methods described previously [ 39 – 41 ]. The HCMEC cell line was used as the negative control.…”

Glycine Promotes the Survival of a Subpopulation of Neural Stem Cells

“…However, the mechanism by which nestin protects cell survival is still unclear. Recent studies reported that nestin interacts with cyclin-dependent kinase 5 and controls cell functions including apoptosis and cell differentiation (Cicero and Herrup, 2005 ; Sahlgren et al, 2006 ), and nestin deletion significantly inhibits the proliferation of colorectal cancer cells by arresting the cell cycle progression at S mitotic phase of division (Li et al, 2015 ). In support of this finding with nestin + NSCs, a recent study revealed connection between nestin and p53 into liver cancer cells, where they showed that p53-dependent nestin regulation in hepatocellular carcinomas and cholangiocarcinomas cells and this connection regulates cellular plasticity and tumorigenesis in liver cancer (Tschaharganeh et al, 2016 ).…”