title: miR-137 inhibits proliferation of melanoma cells by targeting PAK2.
abstract: MicroRNAs (miRNA) are key players in a variety of cancers including malignant melanoma. miR-137 has been reported to be a tumor suppressor in melanoma and several targets have been identified for this miRNA. We previously developed a novel proteomics technology, (35) S in vivo/vitro labelling analysis for dynamic proteomics (SiLAD). Because of its high sensitivity in analysing protein expression rates, SiLAD has the potential to unravel miRNA effects on mRNAs coding for proteins with long half-lives or high abundance. Using SiLAD, we discovered that miR-137 significantly downregulated the expression rate of p21-activated kinase 2 (PAK2) in melanoma cells. Bioinformatics analysis predicted PAK2 as a direct target of miR-137, which was confirmed by luciferase reporter assay and Western blot analysis. We found that overexpression of miR-137 inhibited the proliferation of melanoma cells, which could be phenocopied by knockdown of PAK2 using siRNAs. Furthermore, overexpression of PAK2 restored miR-137-mediated suppression of cell proliferation. These findings indicate that miR-137 could inhibit proliferation through targeting PAK2 in melanoma cells.
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation of Ministry of Education, Universities of the Confederated Institute for Proteomics, Beijing Normal University, Beijing, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of Translational Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Chonglin
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Translational Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Alia
authors.initials: A
authors.lastname: Abukiwan
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation of Ministry of Education, Universities of the Confederated Institute for Proteomics, Beijing Normal University, Beijing, China.
authors.forename: Guangxia
authors.initials: G
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation of Ministry of Education, Universities of the Confederated Institute for Proteomics, Beijing Normal University, Beijing, China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: He
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation of Ministry of Education, Universities of the Confederated Institute for Proteomics, Beijing Normal University, Beijing, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Translational Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Claudia E M
authors.initials: CE
authors.lastname: Weber
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation of Ministry of Education, Universities of the Confederated Institute for Proteomics, Beijing Normal University, Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Lv
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation of Ministry of Education, Universities of the Confederated Institute for Proteomics, Beijing Normal University, Beijing, China.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Translational Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Stefan B
authors.identifier: http://orcid.org/0000-0002-3497-6904
authors.initials: SB
authors.lastname: Eichmüller
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation of Ministry of Education, Universities of the Confederated Institute for Proteomics, Beijing Normal University, Beijing, China.
authors.forename: Dacheng
authors.initials: D
authors.lastname: He
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism
chemical_list: C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; C515907:PAK2 protein, human; D054462:p21-Activated Kinases
keywords: melanoma; miR-137; microRNA; proliferation; proteomics