MicroRNA-181a promotes proliferation and inhibits apoptosis by suppressing CFIm25 in osteosarcoma.

MicroRNA-181a (miR-181a) is upregulated in osteosarcoma, and its overexpression promotes the proliferation and inhibits the apoptosis of osteosarcoma cells. However, the mechanism of miR­181a as an oncogene remains to be fully elucidated in osteosarcoma. Cleavage factor (CF) Im25 links alternative polyadenylation to glioblastoma tumor suppression, however, its role in osteosarcoma has not been reported. In the present study, it was confirmed that the expression of miR­181a was upregulated in osteosarcoma, and that silencing miR­181a inhibited the proliferation and promoted the apoptosis of osteosarcoma cells. miRNAs are short non­coding RNAs, which regulate target mRNAs by binding predominantly to the 3'untranslated region (3'UTR), inducing either translational repression or degradation of the target. In the present study, target genes of miR­181a were screened using miRanda, which is a commonly used prediction algorithm. It was found that miR­181a targeted the 3'UTR of CFIm25 mRNA. Subsequent experiments confirmed that miR­181a downregulated the expression of CFIm25 in osteosarcoma cells. Finally, it was demonstrated that the CFIm25 protein was also downregulated in osteosarcoma tissues, and inhibited the proliferation and promoted the apoptosis of the cells. Elucidating the roles of miR­181a and CFIm25 in osteosarcoma not only assists in further understanding the pathogenesis and progression of this disease, but also offers novel targets for effective therapies.

Targeted therapy for gastric cancer: Current status and future directions (Review).

According to the 2012 statistics of the International Agency for Research on Cancer (IARC), gastric cancer is the fifth most common malignancy, and the third leading cause of cancer-related deaths worldwide. Conventional chemotherapy and radiation have shown limited efficacy for advanced gastric cancer, showing an overall survival (OS) rate of ~10 months. Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2), is the first approved molecularly targeted agent for HER2-overexpressing gastric cancer, which was found to prolong the OS and the progression-free survival (PFS) of patients. However, HER2 overexpression is present only in a minority of patients with gastric cancer. Hence, other targeted agents are urgently needed. Ramucirumab, a novel human IgG1 monoclonal antibody that selectively targets the extracellular domain of VEGF receptor 2 (VEGFR2), is regarded as a new standard second-line treatment for patients with advanced gastric cancer. The combination of two or more targeted agents directed against two different molecular targets may improve the survival of patients with advanced gastric cancer. Although great efforts have been made, the effect of targeted therapy for gastric cancer is limited. One key reason is that participants in clinical trials for new targeted agents were not selected by detection of the targeted molecule. Here, we review clinical trials related to molecular targets such as anti-epidermal growth factor receptor signaling including anti-HER2 and anti-EGFR1, anti-VEGF signaling, anti-mammalian target of rapamycin (mTOR), tyrosine kinase inhibitors (TKIs) and anti-MET.