Advances of exosomes in gastric cancer metastasis and their applications in diagnosis / 中国肿瘤临床

Gastric cancer (GC) is one of the most resistant malignancy to several treatment strategies. In recent years, the morbidity and mortality of GC has stayed high. Surgical resection remains the main treatment option for GC at present. Although chemotherapy, radiotherapy, immunotherapy, and traditional Chinese medicine are used as adjuvant therapies after surgery, the prognosis and five-year survival rate are still low. Currently, there is no effective method for early diagnosis of GC and thus most patients are diagnosed only when the advanced symptoms appear. Exosomes contain and transfer DNA, RNA, proteins, lipids, and other biological macromole-cules. Several studies have found that exosomes are involved in tumor processes including cell proliferation and metastasis. In particu-lar, the abundant biological macromolecules present in the exosomes reflect the progress of tumor development thereby enabling them as non-invasive diagnostic markers. This provides a new idea for diagnosing GC in early stages. In this review, the contribution of exosomes to GC metastasis and the applications of exosomes in early GC diagnosis are briefly summarized.

Simultaneously expressed miR-424 and miR-381 synergistically suppress the proliferation and survival of renal cancer cells---Cdc2 activity is up-regulated by targeting WEE1

OBJECTIVES: MiRNAs are intrinsic RNAs that interfere with protein translation. Few studies on the synergistic effects of miRNAs have been reported. Both miR-424 and miR-381 have been individually reported to be involved in carcinogenesis. They share a common putative target, WEE1, which is described as an inhibitor of G2/M progression. Here, we studied the synergistic effects of miR-424 and miR-381 on renal cancer cells. METHODS: The viability of 786-O cells was analyzed after transfection with either a combination of miR-424 and miR-381 or each miRNA alone. We investigated cell cycle progression and apoptosis with flow cytometry. To confirm apoptosis and the abrogation of G2/M arrest, we determined the level of pHH3, which is an indicator of mitosis, and caspase-3/7 activity. The expression levels of WEE1, Cdc25, γH2AX, and Cdc2 were manipulated to investigate the roles of these proteins in the miRNA-induced anti-tumor effects. To verify that WEE1 was a direct target of both miR-424 and miR-381, we performed a dual luciferase reporter assay. RESULTS: We showed that the combination of these miRNAs synergistically inhibited proliferation, abrogated G2/M arrest, and induced apoptosis. This combination led to Cdc2 activation through WEE1 inhibition. This regulation was more effective when cells were treated with both miRNAs than with either miRNA alone, indicating synergy between these miRNAs. WEE1 was verified to be a direct target of each miRNA according to the luciferase reporter assay. CONCLUSIONS: These data clearly demonstrate that these two miRNAs might synergistically act as novel modulators of tumorigenesis by down-regulating WEE1 expression in renal cell cancer cells. .