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Kleemann, M.* ; Schneider, H.* ; Unger, K. ; Bereuther, J.* ; Fischer, S.* ; Sander, P.* ; Marion Schneider, E.* ; Fischer-Posovszky, P.* ; Riedel, C.U.* ; Handrick, R.* ; Otte, K.*

Induction of apoptosis in ovarian cancer cells by miR-493-3p directly targeting AKT2, STK38L, HMGA2, ETS1 and E2F5.

Cell. Mol. Life Sci. 76, 539-559 (2019)
Postprint DOI PMC
Open Access Green
Apoptosis is a form of directed programmed cell death with a tightly regulated signalling cascade for the destruction of single cells. MicroRNAs (miRNAs) play an important role as fine tuners in the regulation of apoptotic processes. MiR-493-3p mimic transfection leads to the induction of apoptosis causing the breakdown of mitochondrial membrane potential and the activation of Caspases resulting in the fragmentation of DNA in several ovarian carcinoma cell lines. Ovarian cancer shows with its pronounced heterogeneity a very high death-to-incidence ratio. A target gene analysis for miR-493-3p was performed for the investigation of underlying molecular mechanisms involved in apoptosis signalling pathways. Elevated miR-493-3p levels downregulated the mRNA and protein expression levels of Serine/Threonine Kinase 38 Like (STK38L), High Mobility Group AT-Hook 2 (HMGA2) and AKT Serine/Threonine Kinase 2 (AKT2) by direct binding as demonstrated by luciferase reporter assays. Notably, the protein expression of RAF1 Proto-Oncogene, Serine/Threonine Kinase (RAF1) was almost completely downregulated by miR-493-3p. This interaction, however, was indirect and regulated by STK38L phosphorylation. In addition, RAF1 transcription was diminished as a result of reduced transcription of ETS proto-oncogene 1 (ETS1), another direct target of miR-493-3p. Taken together, our observations have uncovered the apoptosis inducing potential of miR-493-3p through its regulation of multiple target genes participating in the extrinsic and intrinsic apoptosis pathway.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Microrna ; Cancer ; Signalling Pathways ; Targets ; Raf1; Recombinant Protein; Microrna; Identification; Proliferation; Migration; Invasion; Pathways; Biogenesis; Suppresses; Resistance
ISSN (print) / ISBN 1420-682X
e-ISSN 1420-9071
Journal Cellular and Molecular Life Sciences - CMLS
Quellenangaben Volume: 76, Issue: 3, Pages: 539-559 Article Number: , Supplement: ,
Publisher Birkhäuser
Publishing Place Picassoplatz 4, Basel, 4052, Switzerland
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Translational Metabolic Oncology (TMO)