| Full text | |
| Author(s): |
Nagahashi Marie, Suely Kazue
[1, 2]
;
Oba-Shinjo, Sueli Mieko
[2]
;
da Silva, Roseli
[2]
;
Gimenez, Marcela
[3, 4]
;
Reis, Gisele Nunes
[2]
;
Tassan, Jean-Pierre
[5]
;
Rosa, Jose Cesar
[3, 4]
;
Uno, Miyuki
[5, 6]
Total Authors: 8
|
| Affiliation: | [1] Univ Sao Paulo, Ctr Studies Cellular & Mol Therapy NETCEM, Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Med, Dept Neurol, Lab Mol & Cellular Biol LIM 15, Av Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Med Sch Ribeirao Preto, Prot Chem Ctr, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto - Brazil
[4] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Mol & Cell Biol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto - Brazil
[5] Univ Rennes 1, Inst Genet & Dev Rennes, UMR CNRS 6290, Cell Cycle Grp, SFR Biosit, 2 Ave Prof Leon Bernard, CS 3431735043 Rennes, Bretagne - France
[6] Inst Canc Estado Sao Paulo, Ctr Translat Res Oncol, Av Dr Arnaldo 251, 8th Floor, BR-01246000 Sao Paulo, SP - Brazil
Total Affiliations: 6
|
| Document type: | Journal article |
| Source: | PROTEOME SCIENCE; v. 14, MAR 11 2016. |
| Web of Science Citations: | 6 |
| Abstract | |
Background: Maternal Embryonic Leucine Zipper Kinase (MELK) is a serine/threonine kinase involved in cell cycle, differentiation, proliferation, and apoptosis. These multiple features are consistent with it being a potential anticancer target. Nevertheless, the MELK pathway in tumorigenesis is not yet completely understood. This study aims to identify proteins associated with MELK pathway in astrocytomas. To this end, proteomic data of the human glioma cell line U87MG transfected with siRNA for MELK were compared with non-target transfected control cells and compared with oligonucleotide microarray data. Results: In both assays, we identified stathmin/oncoprotein 18 (STMN1), involved in cell cycle. STMN1 gene expression was further assessed in a series of 154 astrocytomas and 22 non-neoplastic brain samples by qRT-PCR. STMN1 expression was significantly increased in malignant diffusely infiltrative astrocytomas compared with pilocytic astrocytoma (p < 0.0001). A strong correlation between MELK and STMN1 expressions was observed (r = 0.741, p < 0.0001) in glioblastoma (GBM) samples. However, no difference on survival times was found when compared GBM cases with upregulated and downregulated STMN1 (Breslow = 0.092, median survival time: 11 and 13 months, respectively). Functional assays knocking down MELK by siRNA in GBM cell line showed that gene and protein expression of both MELK and stathmin were diminished. On the other hand, when the same analysis was performed for STMN1, only stathmin gene and protein was silenced. Conclusions: The results presented herein point stahtmin as a downstream target in the MELK pathway that plays a role in malignant progression of astrocytomas. (AU) | |
| FAPESP's process: | 04/12133-6 - Search for molecular markers related to the diagnosis and prognosis of tumors of the central nervous system |
| Grantee: | Suely Kazue Nagahashi Marie |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 12/15896-7 - Expression analysis of genes related to MELK pathway in astrocytomas |
| Grantee: | Miyuki Uno |
| Support Opportunities: | Regular Research Grants |