MicroRNA-340 inhibits the proliferation and promotes the apoptosis of colon cancer cells by modulating REV3L

Roshini Arivazhagan, Jaesuk Lee, Delger Bayarsaikhan, Peter Kwak, Myeongjoo Son, Kyunghee Byun, Ghasem Hosseini Salekdeh, Bonghee Lee*

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Citations (Scopus)
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Abstract

DNA Directed Polymerase Zeta Catalytic Subunit (REV3L) has recently emerged as an important oncogene. Although the expressions of REV3L are similar in normal and cancer cells, several mutations in REV3L have been shown to play important roles in cancer. These mutations cause proteins misfolding and mislocalization, which in turn alters their interactions and biological functions. miRNAs play important regulatory roles during the progression and metastasis of several human cancers. This study was undertaken to determine how changes in the location and interactions of REV3L regulate colon cancer progression. REV3L protein mislocalization confirmed from the immunostaining results and the known interactions of REV3L was found to be broken as seen from the PLA assay results. The mislocalized REV3L might interact with new proteins partners in the cytoplasm which in turn may play role in regulating colon cancer progression. hsa-miR-340 (miR-340), a microRNA down-regulated in colon cancer, was used to bind to and downregulate REV3L, and found to control the proliferation and induce the apoptosis of colon cancer cells (HCT-116 and DLD-1) via the MAPK pathway. Furthermore, this down-regulation of REV3L also diminished colon cancer cell migration, and down-regulated MMP-2 and MMP-9. Combined treatment of colon cancer cells with miR-340 and 5-FU enhanced the inhibitory effects of 5-FU. In addition, in vivo experiments conducted on nude mice revealed tumor sizes were smaller in a HCT-116-miR-340 injected group than in a HCT-116-pCMV injected group. Our findings suggest mutations in REV3L causes protein mislocalization to the cytoplasm, breaking its interaction and is believed to form new protein interactions in cytoplasm contributing to colon cancer progression. Accordingly, microRNA-340 appears to be a good candidate for colon cancer therapy.

Original languageEnglish
Pages (from-to)5155-5168
Number of pages14
JournalOncotarget
Volume9
Issue number4
DOIs
Publication statusPublished - 12 Jan 2018

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Copyright the Author(s). Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • REV3L
  • mislocalization
  • interactions
  • colon cancer
  • miR-340

Cite this

Arivazhagan, R., Lee, J., Bayarsaikhan, D., Kwak, P., Son, M., Byun, K., ... Lee, B. (2018). MicroRNA-340 inhibits the proliferation and promotes the apoptosis of colon cancer cells by modulating REV3L. Oncotarget, 9(4), 5155-5168. https://doi.org/10.18632/oncotarget.23703