Oncotarget

Research Papers:

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 and Bonghee Lee _

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Oncotarget. 2018; 9:5155-5168. https://doi.org/10.18632/oncotarget.23703

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Abstract

Roshini Arivazhagan1, Jaesuk Lee1, Delger Bayarsaikhan1, Peter Kwak1, Myeongjoo Son1,2, Kyunghee Byun1,2, Ghasem Hosseini Salekdeh3,4 and Bonghee Lee1,2

1Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea

2Department of Anatomy and Cell Biology, Gachon University Graduate School of Medicine, Incheon, Republic of Korea

3Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

4Department of Molecular Sciences, Macquarie University Sydney, New South Wales, Australia

Correspondence to:

Bonghee Lee, email: bhlee@gachon.ac.kr

Ghasem Hosseini Salekdeh, email: Salekdeh@royaninstitute.org

Kyunghee Byun, email: khbyun1@gachon.ac.kr

Keywords: REV3L; mislocalization; interactions; colon cancer; miR-340

Received: May 02, 2017     Accepted: December 05, 2017     Published: December 26, 2017

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.


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