[Jan 16th 2019] LabMeeting: Study of potential impact of copy number alterations of MAPK15 in High Grade Serous Ovarian Cancer

Giorgia Giacomini (DIISM, University of Siena)

Jan 16, 2019 – 11:00 AM
DIISM, Artificial Intelligence laboratory (room 201), Siena SI

A powerful way to discover key genes playing causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Copy Number Alterations (CNAs) are structural rearrangements involving DNA segments, of at least 50 bp, that can be present with an altered copy number compared to the reference genome. They can also involve large regions and include deleted or duplicated genes. Pathogenic CNAs are often associated with unfavorable cancer prognosis. Therefore, both the detection and the characterization of CNAs are fundamental for personalized treatments.

Mitogen-activated protein (MAP) kinases are a family of proline-directed serine/threonine kinases expressed in eukaryotic cells and involved in key signaling pathways regulating cell proliferation, differentiation, apoptosis, and stress response. MAPK15 is the last identified member of the MAP kinase family and, although its role in the regulation of several processes, such as autophagy and ciliogenesis, is known, its molecular function still deserves some clarification [1]. MAPK15 is able to interacts with SRC, TGFB1I1, ESRRA, PCNA, and GABARAP through domains in its C-terminal region and plays roles in cell pathophysiological processes. Moreover, recent studies have demonstrated that MAPK15 is involved in tumorigenesis by regulating several signal pathways such as c-Jun activity and telomerase activity [2].

In the present study, we have employed The Cancer Genome Atlas (TCGA, https://cancergenome.nih.gov/) data to compare the expression, methylation, and mutational levels of MAPK15 among all cancer types and to better investigate the molecular basis of its role in oncogenesis. Higher frequency of alteration and higher level of expression of MAPK15 are found in ovarian cancer across all TCGA projects, which seems to confirm its role in biological process involved this type of cancer. Moreover, the positive value of correlation analysis suggests that the CNA of MAPK15 can influence the gene at transcriptional level and can be associated with the ovarian cancer progression. Finally, the functional analysis of upregulated and downregulated genes showed that the CNA of MAPK15 can influence the expression of other genes implicated in essential cellular processes involving cell communication, particularly cell-cell signaling and signal transduction, fundamental pathways for cancer development.

[1] Abe M.K., Saelzler M.P., Espinosa R., Kahle K.T., Hershenson M.B., Le Beau M.M., Rosner M.R., “ERK8, a new member of the mitogen-activated protein kinase family”, J. Biol. Chem., 277:16733-43; PMID:11875070; http://dx.doi.org/10.1074/jbc.M112483200, 2002.

[2] Dong-Hao Jin, Joobae Park, Duk-Hwan Kim, “MAPK15 is an attractive therapeutic target for gastric cancer”, Cancer Cell & Microenvironment, 2: e1006. doi: 10.14800/ccm.1006, 2015.

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