Downregulation of miR-34a distinguished between patients with bladder cancer and the healthy controls. miR-34a expression was associated with tumor metastasis; however, not with tumor size.
High miR-34a expression was associated with better survival of patients. miR-34a showed lower expression levels in male patients with lymph node involvement, and a trend towards decreased expression in male patients with distant metastases.
Combined inactivation of the microRNA 34a gene (MIR34A, by methylation) and the TP53 gene (by mutation or deletion) is observed in 50% of colorectal tumors that progress to distant metastases.
Here, the potential association between aberrant miR-34 expression and promoter methylation and distant metastases formation in lung adenocarcinoma (LAC) is investigated.
MRX34, a liposome-formulated mimic of miR-34 for treatment of metastatic cancer with liver involvement and unresectable primary liver cancer, has also entered in clinical trial.
Finally, we introduce methods to study TGF-β-regulated miRNAs and their functions in tumor progression and metastasis using an example of publication from our lab demonstrating the presence of a TGF-β-miR-34a-CCL22 signaling axis, which serves as a potent etiological pathway for the development of hepatocellular carcinoma venous metastases.
We also showed that HOTAIR recruiting and binding to PRC2 epigenetically represses miR34a, which controls the targets C-Met (HGF/C-Met/Snail pathway) and Snail, thus contributing to GC cell-EMT process and accelerating tumor metastasis.
Decreased miR-34a expression was associated with upregulation of c-Met, Snail, and β-catenin protein levels (P = 0.031, 0.132, and 0.004), which were associated with distant metastases (P = 0.001, 0.017, and 0.005).
In breast cancer patients, the changes in the levels of total RNA (P = 0.0001), miR10b (P = 0.01), miR34a (P = 0.003) and miR155 (P = 0.002) correlated with the presence of overt metastases.