MicroRNA-106a-5p (MiR-106a-5p), a small non-coding RNA, has been reported to be downregulated in astrocytoma, osteosarcoma and colorectal cancer. However, the expression levels and biological function in renal cell carcinoma (RCC) have not been studied yet. In this study, we found that the miR-106a-5p was significantly downregulated in RCC tissues and cell lines, and that overexpression of miR-106a-5p led to decreased cell metastasis ability in a xenograft model. Inhibition of miR-106a-5p in RCC cell lines altered the cell migration, invasion and wound healing abilities. Mechanistic studies demonstrated that miR-106a-5p directly bound to the 3′-UTR of the PAK5 mRNA and mediated a decrease in the protein expression of PAK5. We further proved that PAK5 protein levels were negatively correlated with the miR-106a-5p expression in both patient samples and xenograft model. In epigenetics, methylation specific PCR experiments indicated that the upstream gene promoter of miR-106a-5p was hypermethylated in RCC, which might be responsible for its downregulation. Our findings suggested that miR-106a-5p might be a potential gene therapy target for the treatment of RCC metastasis.

N6-methyladenosine (m 6 A) is identified as the most prevalent and abundant internal RNA modification, especially within eukaryotic mRNAs, which has attracted much attention in recent years since its importance for regulating gene expression and deciding cell fate. m 6 A modification is installed by RNA methyltransferases METTL3, METTL14 and WTAP (Writers), removed by the demethylases FTO and ALKBH5 (Erasers) and recognized by m 6 A binding proteins, such as YT521-B homology YTH domain-containing proteins (Readers). Accumulating evidence shows that m 6 A RNA methylation participates in almost all aspects of RNA processing, implying an association with important bioprocesses. In this review, we mainly summarize and discuss the functional relevance and importance of m 6 A modification in cellular processes.

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BackgroundAbnormal proliferation is significantly associated with the promotion of malignant tumor. Growing evidence suggest that the signal pathways of p21cdc42/rac1-activated kinase 5 (PAK5) have been found in various tumor progression, however, the role of PAK5 in breast cancer remains largely unclear.MethodsWe evaluated PAK5 and p65 staining in breast cancer tissues (BCTs) and paired non-cancerous tissues (NTs) using tissue microarray (TMA) technology. The functions of PAK5 were studied in vitro and in vivo. Cell Counting Kit-8 (CCK-8) and flow cytometry were performed to determine proliferation of breast cancer cells. Phosphorylation assay and co-immunoprecipitation (co-IP) were employed to identify the regulation mechanism of p65 by PAK5. The activation of Cyclin D1 promoter was measured with luciferase reporter assay. Xenograft models in nude mice were established to explore the roles of PAK5 in breast cancer growth.ResultsIn this study, we show that PAK5 is highly expressed in breast cancer tissues and the increased PAK5 is significantly associated with breast cancer progression. Overexpression of PAK5 promotes the proliferation and cell-cycle progression by increasing the expression of Cyclin D1 in vitro and in vivo. Mechanistic studies demonstrated that PAK5 can promote the phosphorylation and the nuclear translocation of p65 subunit of nuclear factor-kappaB (NF-κB). Furthermore, p65 can directly bind to the promoter of Cyclin D1 and mediate an increase in its protein expression.ConclusionsTaken together, our findings suggest that PAK5 may serve as a potential prognosis marker and therapeutic target for human breast cancer.

Our results suggested that MicroRNA-9-TNFAIP8 might represent a promising diagnostic biomarker for GC patients and could be a potential therapeutic target in the prevention and treatment of GC.