Journal of Cell Communication and Signaling

, Volume 12, Issue 2, pp 451–466 | Cite as

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

  • Marion Flum
  • Michael KleemannEmail author
  • Helga Schneider
  • Benjamin Weis
  • Simon Fischer
  • René Handrick
  • Kerstin Otte
Research Article


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.


Apoptosis Cell death Colorectal cancer miR-217-5p Target analysis 



Astrocyte-elevated gene-1


Activating protein-1


BAG family molecular chaperone regulator 3


Baculoviral IAP repeat containing 2


BRCA1 DNA repair associated


Carbonyl cyanide m-chlorophenyl hydrazine


Colorectal cancer


Catenin beta 1


Dimethyl sulfoxide


Death inducing


Epidermal growth factor receptor


Ets like protein 1


Extracellular-signal regulated kinase


Fetal calf serum


Fluorescein isothiocyanate


Glyceraldehyde 3-phosphate dehydrogenase


Horseradish peroxidase


Integrin subunit alpha v


Mitogen-activated protein kinase 1




Mitochondrial membrane potential


Transcriptional activator MYC


Nuclear factor-kappa B




Poly (ADP-ribose) polymerase


Phosphate-buffered saline


Propidium iodide


Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha


Peptidylprolyl isomerase A


Protein kinase c iota type I




Ras-related C3 botulinum toxin substrate 1


Raf-1 proto-oncogene, serine/threonine kinase


Sodium dodecyl sulfate polyacrylamide gel electrophoresis


Small interfering RNA


Sex determining region Y-box 2


Transforming growth factor beta receptor 2


Tetramethylrhodamine ethyl ester perchlorate


Tumor necrosis factor related apoptosis inducing ligand


Untranslated region



HCT 116 cells were kindly provided by Prof. Dr. Verena Jendrossek, IFZ, University of Duisburg-Essen and HT-29 and SW480 were kindly provided by Prof. Dr. Uwe Knippschild, University Hospital Ulm.


This study was funded by the Postgraduate Scholarships Act of the Ministry for Science, Research and Arts of the federal state government of Baden-Wuerttemberg, Germany. Further acknowledgements address the International Graduate School in Molecular Medicine of Ulm University, Germany, for scientific encouragement and support to Michael Kleemann.

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict of interest.


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Copyright information

© The International CCN Society 2017

Authors and Affiliations

  • Marion Flum
    • 1
    • 2
  • Michael Kleemann
    • 1
    Email author
  • Helga Schneider
    • 1
  • Benjamin Weis
    • 1
  • Simon Fischer
    • 3
  • René Handrick
    • 1
  • Kerstin Otte
    • 1
  1. 1.Institute of Applied BiotechnologyUniversity of Applied Sciences BiberachBiberachGermany
  2. 2.Faculty of MedicineUniversity of UlmUlmGermany
  3. 3.Boehringer Ingelheim Pharma GmbH & Co KG, Cell Culture Development CMBBiberachGermany

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