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Sodium Butyrate Inhibits the Malignant Proliferation of Colon Cancer Cells via the miR-183/DNAJB4 Axis

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Abstract

Colorectal carcinoma (CRC) is one of the most common malignant tumors in the digestive tract. It was found that butyric acid could inhibit the expression of miR-183 to slow down malignant progression of CRC in the early stage. However, its regulatory mechanism remains unclear. This study screened the IC50 value of butyrate on inhibition of CRC cells malignant progression. Its inhibitory effects were detected by MTT assay, colony formation experiment, Transwell migration experiment, and apoptosis evaluation by flow cytometry. Next, the expressions of miR-183 and DNAJB4 were, respectively, determined in butyrate treated and miR-183 analog or si-DNAJB4-transfected CRC cells to further detect the role of upregulated miR-183 or silencing DNAJB4 in CRC cells malignant progression. Subsequently, the targeted regulatory relationship between miR-183 and si-DNAJB4 was confirmed by bioinformatic prediction tools and double luciferase report genes analysis method. The regulatory mechanism of butyrate on miR-183/DNAJB4 axis signal pathway was evaluated in molecular level, and verified in nude mouse xerograft tumor model and immunohistochemical analysis tests of Ki67 positive rates. The results displayed that butyrate with increased concentration can hinder the proliferation and improve apoptosis of CRC cells by decreasing the expression of miR-183. Thus, butyrate reduces miR-183 expression and increases DNAJB4 expression via the miR-183/DNAJB4 axis, ultimately inhibiting the malignant progression and increasing apoptosis of CRC. While over expression of miR-183 downregulate the expression of DNAJB4, which can reverse the inhibitory effect of butyrate.

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Data Availability

The data used to support the findings of this study are available upon request to the corresponding author.

Abbreviations

miRs:

microRNAs

agomiR:

miRNA agomir

agomiR-NC:

miRNA-normal control agomir

agomiR-183:

miRNA-183 agomir

CRC:

Colorectal cancer

DMEM:

Dulbecco's modified Eagle's medium

DMSO:

Dimethyl Sulfoxide

DNA:

Deoxyribonucleic acid

GAPDH:

Glyceraldehyde phosphate dehydrogenase

GLOBOCAN:

The Global Cancer Epidemiology Statistics

HDAC:

Histone deacetylatase

IARC:

International Agency for Research on Cancer

IC50 :

Half maximal inhibitory concentration

MiR-183:

microRNA-183

mRNA:

Messenger ribonucleic acid

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

OD:

Optical density

PBS:

Phosphate Buffered Saline

RNA:

Ribonucleic acid

RT-qPCR:

Reverse transcription quantitative polymerase chain reaction

RPMI-1640:

Roswell Park Memorial Institute-1640

SCFA:

Short-chain volatile fatty acid

TRIzol:

Total RNA extraction reagent

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Funding

This project was supported by the Fund of Department of Science and Technology Program of Yunnan Province (202001AY070001-236), the Joint Special Fund of Applied Basic Research of Department of Science and Technology & Kunming Medical University 2019FE001(-134), the Fund of Department of Science and Technology Program of Yunnan Province (202101AT070170) and the Open Fund of School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products (YKLPNP-G2304).

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Authors and Affiliations

  1. Department of Colorectal Surgery, Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, China

    Dingguo Pan, Tao Wu, Tao Shen, Kun Yu, Qiang Li, Ruixi Hu, Zhaoyu Yang & Yunfeng Li

  2. School of Pharmaceutical Science & Key Laboratory of Natural Pharmacology of Yunnan Province, Kunming Medical University, Kunming, 650500, Yunnan, China

    Jingchao Hao

  3. Kunming Medical University, Kunming, 650500, Yunnan, China

    Dingguo Pan, Jingchao Hao & Zhaoyu Yang

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  1. Dingguo Pan
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  3. Tao Wu
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  4. Tao Shen
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  5. Kun Yu
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Contributions

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Study conception and design: DP, JH, ZY, YL. Acquisition of data: DP, JH, TW, TS, KY. Analysis and interpretation of data: DP, TW, TS, KY, QL, RH.

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Correspondence to Yunfeng Li.

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The authors declare no competing interests.

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The authors declare no conflict of interest. All authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or a financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

F forward; R reverse; miR micoRNA; GAPDH glyceraldehyde phosphate dehydrogenase.

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Dingguo Pan and Jingchao Hao are co-first authors.

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Pan, D., Hao, J., Wu, T. et al. Sodium Butyrate Inhibits the Malignant Proliferation of Colon Cancer Cells via the miR-183/DNAJB4 Axis. Biochem Genet (2024). https://doi.org/10.1007/s10528-023-10599-z

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