MAPK13

Abstract: The critical role of microRNAs in cancer development has been extensively described. miRNAs are both specific markers and putative therapy targets. miR-155 has been identified to be an oncomiRNA and is highly expressed in several solid cancers, including glioblastoma. In this study, we found that miR-155 is a good potential therapy target. Knockdown of miR-155 sensitizes glioma cells to the chemotherapy of temozolomide (TMZ) by targeting the p38 isoforms mitogen-activated protein kinase 13 [MAPK13, also known as p38 MAPKδ or stress-activated protein kinase 4 (SAPK4)] and MAPK14 (also known as p38 MAPKα). As tumor suppressor genes, MAPK13 and MAPK14 play important roles in lowering the accumulation of reactive oxygen species (ROS), inducing cell apoptosis, and slowing the progression of cancer. Knockdown of miR-155 enhanced the anticancer effect of TMZ on glioma by targeting the MAPK13 and MAPK14-mediated oxidative stress and apoptosis, but did not affect the secretion of MMP2 and MMP9.

Abstract: The molecular mechanisms of osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remain to be fully elucidated. MicroRNAs (miRs) serve vital roles in the process of regulating osteogenic differentiation of BMSCs. The present study aimed to investigate the role of miR‑23a‑5p in osteogenic differentiation of human (h)BMSCs, and the underlying molecular mechanism. The results of reverse transcription‑quantitative polymerase chain reaction demonstrated that miR‑23a‑5p was significantly downregulated in the process of osteogenic differentiation. Upregulation of miR‑23a‑5p inhibited osteogenic differentiation of hBMSCs, and down‑regulated expression of miR‑23a‑5p enhanced this process, which was confirmed by alkaline phosphatase (ALP) and Alizarin Red S staining. A dual‑luciferase reporter assay confirmed that mitogen‑activated protein kinase 13 (MAPK13) was a direct target of miR‑23a‑5p. In addition, knockdown of MAPK13 inhibited osteogenic differentiation of hBMSCs, similar to the effect of upregulation of miR‑23a‑5p. Finally, the knockdown of MAPK13 also blocked the effect of miR‑23a‑5p in osteogenic differentiation of hBMSCs, which was also confirmed by ALP and Alizarin Red S staining. These results indicated that by targeting MAPK13, miR‑23a‑5p serves a vital role in osteogenic differentiation of hBMSCs, which may provide novel clinical treatments for bone injury however, further studies are required.

Abstract: The comparison of organ transcriptomes is an important strategy for understanding gene functions. In the present study, we attempted to identify lung-prominent genes by comparing the normal transcriptomes of rat lung, heart, kidney, liver, spleen, and brain. To increase the efficiency and reproducibility, we first developed a novel parallel hybridization system, in which 6 samples could be hybridized onto a single slide at the same time. We identified the genes prominently expressed in the lung (147) or co-expressed in lung-heart (23), lung-liver (37), lung-spleen (203), and lung-kidney (98). The known functions of the lung-prominent genes mainly fell into 5 categories: ligand binding, signal transducer, cell communication, development, and metabolism. Real-time PCR confirmed 13 lung-prominent genes, including 5 genes that have not been investigated in the lung, vitamin D-dependent calcium binding protein (Calb3), mitogen activated protein kinase 13 (Mapk13), solute carrier family 29 transporters, member 1 (Slc29a1), corticotropin releasing hormone receptor (Crhr1), and lipocalin 2 (Lcn2). The lung-prominent genes identified in this study may provide an important clue for further investigation of pulmonary functions.

Abstract: The p38δ mitogen-activated protein kinase is an important signal transduction enzyme. p38δ has recently emerged as a drug target due to its tissue-specific expression patterns and its critical roles in regulation of cellular processes related to cancer and inflammatory diseases, such as cell proliferation, cell migration, apoptosis, and inflammatory responses. However, potent and specific p38δ inhibitors have not been defined so far. Moreover, in cancer disease, p38δ appears to act as a tumor suppressor or tumor promoter according to cancer and cell type studied. In this review, we outline the current understanding of p38δ roles in each cancer type, to define whether it is possible to delineate new cancer therapies based on small-molecule p38δ inhibitors. We also highlight recent advances made in the design of molecules with potential to inhibit p38 isoforms and discuss structural approaches to guide the search for p38δ inhibitors.