miR-217-5p induces apoptosis by directly targeting PRKCI, BAG3, ITGAV and MAPK1 in colorectal cancer cells

• Published in: Journal of cell communication and signaling 2018-06, Vol.12 (2), p.451-466
• Main Authors: Flum, Marion, Kleemann, Michael, Schneider, Helga, Weis, Benjamin, Fischer, Simon, Handrick, René, Otte, Kerstin
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomedical and Life Sciences; Biomedicine; Carcinogenesis; Cell Biology; Cell death; Colorectal cancer; Colorectal carcinoma; Deoxyribonucleic acid; DNA; DNA fragmentation; Extracellular signal-regulated kinase; Gene expression; Gene regulation; Kinases; Life Sciences; MAP kinase; Membrane potential; miRNA; miR‐217‐5p; Mitochondria; mRNA; Nucleotides; Phosphatidylserine; Protein kinase C; Proteins; Research Article; Signal transduction; Target analysis; Therapeutic applications; Transfection; Tumor cell lines
• ISSN: 1873-9601; 1873-961X
• DOI: 10.1007/s12079-017-0410-x

Apoptosis is a genetically directed process of programmed cell death. A variety of microRNAs (miRNAs), endogenous single-stranded non-coding RNAs of about 22 nucleotides in length have been shown to be involved in the regulation of the intrinsic or extrinsic apoptotic pathways. There is increasing evidence that the aberrant expression of miRNAs plays a causal role in the development of diseases such as cancer. This makes miRNAs promising candidate molecules as therapeutic targets or agents. MicroRNA (miR)-217-5p has been implicated in carcinogenesis of various cancer entities, including colorectal cancer. Here, we analyzed the pro-apoptotic potential of miR-217-5p in a variety of colorecatal cancer cell lines showing that miR-217-5p mimic transfection led to the induction of apoptosis causing the breakdown of mitochondrial membrane potential, externalization of phosphatidylserine, activation of caspases and fragmentation of DNA. Furthermore, elevated miR-217-5p levels downregulated mRNA and protein expression of atypical protein kinase c iota type I (PRKCI), BAG family molecular chaperone regulator 3 (BAG3), integrin subunit alpha v (ITGAV) and mitogen-activated protein kinase 1 (MAPK1). A direct miR-217-5p mediated regulation to those targets was shown by repressed luciferase activity of reporter constructs containing the miR-217-5p binding sites in the 3′ untranslated region. Taken together, our observations have uncovered the apoptosis-inducing potential of miR-217-5p through its regulation of multiple target genes involved in the ERK-MAPK signaling pathway by regulation of PRKCI, BAG3, ITGAV and MAPK1.