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MicroRNA 429 regulates the expression of CHMP5 in the inflammatory colitis and colorectal cancer cells

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Abstract

Objective and design

MicroRNAs (miRNAs) play an important role in the pathogenesis of human diseases by regulating the expression of target genes in specific cells or tissues. In this study, we analyzed the association between the MIR429 and its target gene, charged multivesicular body protein 5 (CHMP5), in human colon cancer cells and in a DSS-induced colitis mouse model.

Materials and methods

A luciferase reporter system was used to confirm the effect of MIR429 on CHMP5 expression. Protein or mRNA expression of the target gene and associated molecules were measured by Western blot or quantitative RT-PCR (qRT-PCR), respectively. Flow cytometry was used to compare cell viability or cell cycle progression.

Results

CHMP5 mRNA and protein expression was directly down-regulated by MIR429. We found that MIR429 inhibited colon cancer cell growth and cell cycle progression, and CHMP5 was overexpressed in the DSS-induced colitis mouse model and human ulcerative colitis (UC) tissues.

Conclusions

Our findings show that CHMP5 is a direct target of MIR429 in human colon cancer cell lines and suggest that CHMP5 up-regulation as a result of reduced MIR429 expression in DSS-induced mice colitis tissues and human UC tissues may restrict apoptosis and promote cell proliferation.

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Acknowledgements

The biospecimens for this study were provided by the Biobank of Wonkwang University Hospital, a member of the National Biobank of Korea, which is supported by the Ministry of Health and Welfare. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, and Future Planning (2017R1A2B4004801).

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Authors and Affiliations

  1. Department of Pathology, School of Medicine, Wonkwang University, Iksan, Chonbuk, 54538, Republic of Korea

    Ji-Su Mo, Seol-Hee Han, Ki-Jung Yun & Soo-Cheon Chae

  2. Digestive Disease Research Institute, Wonkwang University, Iksan, Chonbuk, 54538, Republic of Korea

    Ji-Su Mo & Soo-Cheon Chae

Authors
  1. Ji-Su Mo
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  2. Seol-Hee Han
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Correspondence to Soo-Cheon Chae.

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The authors have no conflict of interest to disclose.

Ethical standards

This research was conducted with the approval of the institutional review board (IRB) of Wonkwang University.

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Responsible Editor: John Di Battista.

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11_2018_1194_MOESM1_ESM.tif

Fig. S1 The immunohistochemistry results of LCA and CHMP5 in DSS-induced mice colitis and human UC colon tissue. (A) H&E staining of DSS-induced colitis colon and normal colon consecutive tissue. Inflammation was observed in DSS-induced colitis colon tissue (single head arrow). LCA and CHMP5 expression levels in DSS-induced colitis colons (double head arrow) are higher than that of normal colons (single head arrow). (B) The immunohistochemistry results of CHMP5 in six human UC colon tissues and six normal colon tissues (×400). The CHMP5 expression levels are significantly increased by the severity of inflammation in the lamina propria of human colon (TIF 750 KB)

Supplementary material 2 (TIF 718 KB)

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Mo, JS., Han, SH., Yun, KJ. et al. MicroRNA 429 regulates the expression of CHMP5 in the inflammatory colitis and colorectal cancer cells. Inflamm. Res. 67, 985–996 (2018). https://doi.org/10.1007/s00011-018-1194-z

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  • DOI: https://doi.org/10.1007/s00011-018-1194-z

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