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CBX8 acts as an independent RNA-binding protein to regulate the maturation of miR-378a-3p in colon cancer cells

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Abstract

CBX8 is the core component of the PCG family protein PRC1 complex. It is overexpressed in many solid tumors and plays an important role in the prognosis and biological behaviors of tumors such as occurrence, development, invasion, and metastasis. However, exploration of the role and molecular mechanism of CBX8 in tumors is still in its infancy. Our study found that the down-regulation of CBX8 expression by RNA interference induced differential expression of several microRNAs in human colon cancer cells. The 5 most differentially expressed miRNA precursors (pre-miRNA) (hsa-miR-363-3p, hsa-miR-378a-3p, hsa-miR-371b-3p, hsa-miR-361-3p, and hsa-miR-576-3p) share a common motif sequence: ARAAAKUGCMC. We selected miR-378a-3p and further revealed that the negative regulation of miRNA expression by CBX8 mainly occurs in the processing of pre-miRNA to mature miRNA. CBX8 uses its own RNA-binding domain to interact with pre-miRNA, and is dependent on its own nuclear localization characteristics to limit nucleoplasmic transport of pre-miRNA. Changing the characteristic sequence of pre-miRNA or mutating the RNA-binding domain and nuclear localization signal of CBX8 can effectively weaken the regulation of miR-378a-3p expression by CBX8. However, our experimental results showed that miR-378a-3p inhibited the malignant expression of human colon cancer cells by targeting PDIA4, resulting in increased activity of caspases-3 and -7. In summary, our study suggests that CBX8 acts as an independent RNA-binding protein to regulate miRNA expression. Simultaneously, this study shows the correlation between the CBX8/miR-378a-3p/PDIA4 pathway and the malignant biological properties of colorectal cancer, suggesting this proposed pathway as a possible therapeutic target for human cancers.

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Acknowledgements

Thanks for technical supporting by Beijing Genex Health Co., Ltd. We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of General Surgery, China-Japan Friendship Hospital, No.2 East Yinghua Road, Chaoyang District, Beijing, 100029, China

    Xin Song, Wu Ning, Jinwei Niu, Guochao Zhang, Haibin Liu & Lei Zhou

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  1. Xin Song
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  2. Wu Ning
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  3. Jinwei Niu
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  4. Guochao Zhang
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  5. Haibin Liu
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  6. Lei Zhou
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Correspondence to Lei Zhou.

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The present study was approved by the Ethics Committee of China–Japan Friendship Hospital and informed consent was provided by patients included in this study.

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Song, X., Ning, W., Niu, J. et al. CBX8 acts as an independent RNA-binding protein to regulate the maturation of miR-378a-3p in colon cancer cells. Human Cell 34, 515–529 (2021). https://doi.org/10.1007/s13577-020-00477-w

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  • DOI: https://doi.org/10.1007/s13577-020-00477-w

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