miR‐298 plays a pivotal role in colon cancer invasiveness by targeting PTEN

다국어 초록 (Multilingual Abstract)

Evidence indicate that the miR‐298 dysregulation might associate with colorectal cancer (CRC) development. Herein, we evaluated the effect of miR‐298 dysregulation on colon cancer invasiveness. First, metabolic activity, cell cycle progression, apoptosis, and invasion of miR‐298 overexpressed/knocked out colon cancer cells were examined and combined with their transcriptome analysis data for better visualization of miR‐298 intracellular signaling networks. Interaction between miR‐298 and its target was evaluated with luciferase assay and validated using western blot analysis. The proportion of abnormal miR‐298 level was investigated in tumor samples, matched normal adjacent tissues, and plasmas of 100 CRC patients, and also compared with 100 normal plasma samples. The Mann–Whitney U test was performed to assess miR‐298 differences among the studied groups, and the correlation between miR‐298 and the risk of CRC was shown by univariate and multivariate logistic regression. The data indicate that miR‐298 overexpression promoted proliferation and metastasis in CRC cells via targeting phosphatase and tensin homolog. Comparative analysis of CRC tumors, normal adjacent tissues, and plasmas indicated a significant miR‐298 upregulation in tumors and plasmas (1.72‐fold and 1.65‐fold, respectively; p < .001). Also, the aberrant level of miR‐298 contributed with CRC tumor differentiation, TNM stage and lymph node metastasis (p < .001), and independently associated with poor survival of CRC patients (p < .029; hazard ratio: 1.292; 95% confidence interval: 0.339–2.184). Collectively, these data showed that abnormal level of miR‐298 correlated with cancer development and through that lowered the overall survival rate of CRC patients. Therefore, miR‐298 could be considered as a therapeutic target for CRC.
The aberrant level of miR‐298 increases the colon cancer cells proliferation and metastasis through downregulation of phosphatase and tensin homolog, and subsequent elevation of phosphorylated activation of Akt/ERK and Akt/mTOR/p70 S6K axis.