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miR-135b Aggravates Fusobacterium nucleatum-Induced Cisplatin Resistance in Colorectal Cancer by Targeting KLF13

  • Microbial Genetics, Genomics and Molecular Biology
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Abstract

Cisplatin resistance is the main cause of colorectal cancer (CRC) treatment failure, and the cause has been reported to be related to Fusobacterium nucleatum (Fn) infection. In this study, we explored the role of Fn in regulating cisplatin resistance of CRC cells and its underlying mechanism involved. The mRNA and protein expressions were examined by qRT-PCR and western blot. Cell proliferation and cell apoptosis were assessed using CCK8 and flow cytometry assays, respectively. Dual-luciferase reporter gene assay was adopted to analyze the molecular interactions. Herein, our results revealed that Fn abundance and miR-135b expression were markedly elevated in CRC tissues, with a favorable association between the two. Moreover, Fn infection could increase miR-135b expression via a concentration-dependent manner, and it also enhanced cell proliferation but reduced apoptosis and cisplatin sensitivity by upregulating miR-135b. Moreover, KLF13 was proved as a downstream target of miR-135b, of which overexpression greatly diminished the promoting effect of miR-135b or Fn-mediated cisplatin resistance in CRC cells. In addition, it was observed that upstream 2.5 kb fragment of miR-135b promoter could be interacted by β-catenin/TCF4 complex, which was proved as an effector signaling of Fn. LF3, a blocker of β-catenin/TCF4 complex, was confirmed to diminish the promoting role of Fn on miR-135b expression. Thus, it could be concluded that Fn activated miR-135b expression through TCF4/β-catenin complex, thereby inhibiting KLF13 expression and promoting cisplatin resistance in CRC.

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The data underlying this article will be shared on reasonable request to the corresponding author.

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Acknowledgements

The study was supported by Changsha Natural Science and Technology Foundation (kq2208451).

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Authors and Affiliations

  1. Department of Gastroenterology, Changsha First Hospital, Changsha, 410005, Hunan, People’s Republic of China

    Wei Zeng, Jia Pan & Guannan Ye

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  1. Wei Zeng
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  2. Jia Pan
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  3. Guannan Ye
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Contributions

Conception and design of study: WZ.  Acquisition of data: JP.  Analysis and interpretation of data: GY.  Drafting the manuscript: JP.  Revising the manuscript critically for important intellectual content: WZ.  All authors reviewed the manuscript.

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Correspondence to Wei Zeng.

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This study was passed the review of Ethics Committee of Changsha First Hospital before enrollment of patients and all participants signed informed consent (Approval Number: No. 2022-171).

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Zeng, W., Pan, J. & Ye, G. miR-135b Aggravates Fusobacterium nucleatum-Induced Cisplatin Resistance in Colorectal Cancer by Targeting KLF13. J Microbiol. 62, 63–73 (2024). https://doi.org/10.1007/s12275-023-00100-1

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