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FIT links c-Myc and P53 acetylation by recruiting RBBP7 during colorectal carcinogenesis

Abstract

Colorectal cancer (CRC) poses one of the most serious threats to human health worldwide, and abnormally expressed c-Myc and p53 are deemed the pivotal driving forces of CRC progression. In this study, we discovered that the lncRNA FIT, which was downregulated in CRC clinical samples, was transcriptionally suppressed by c-Myc in vitro and promoted CRC cell apoptosis by inducing FAS expression. FAS is a p53 target gene, and we found that FIT formed a trimer with RBBP7 and p53 that facilitated p53 acetylation and p53-mediated FAS gene transcription. Moreover, FIT was capable of retarding CRC growth in a mouse xenograft model, and FIT expression was positively correlated with FAS expression in clinical samples. Thus, our study elucidates the role of the lncRNA FIT in human colorectal cancer growth and provides a potential target for anti-CRC drugs.

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Fig. 1: FIT shows a tumour-suppressive effect.
Fig. 2: FIT induces FAS expression by regulating p53.
Fig. 3: The FIT-RBBP7-p53 trimer enhances p53 acetylation and FAS transcription.
Fig. 4: FIT is transcriptionally regulated by c-Myc.
Fig. 5: FIT retards CRC cell xenograft growth, and FIT expression is correlated with c-Myc and FAS expression.
Fig. 6: Working model of FIT in CRC progression.

Data availability

All data generated or analysed during this study are included in this published article and its Supplementary Files.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (82002968, 82022054), Anhui Science Fund for Distinguished Young Scholars (2008085J36), Natural Science Foundation of Anhui Province (2008085QC113) and the Project for Enhancing Scientific Research of Anhui Medical University (2020xkjT015).

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Authors

Contributions

H.G., L.G., and W.H. designed the research. L.G., Y.X., Z.W., and H.L. performed the experiments. H.X., X.D., Y.Z., W.F., and F.W. provided technical assistance. H.Z., L.Z., and S.Z. collected the clinical samples. H.G., W.H., L.G., S.Z., Q.L., and L.C. analysed the data. H.G. wrote the manuscript.

Corresponding authors

Correspondence to Shangxin Zhang, Wanglai Hu or Hao Gu.

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The authors declare no competing interests.

Ethics approval

Four cases of colorectal cancer patients were selected in the First Affiliated Hospital of Anhui Medical University from October 2020 to July 2021. The colorectal cancer was evidenced by histopathology and the patients with a history of other tumours or serious organic disease were excluded. Sample IDs were coded and the investigator was not aware of the group allocation during data acquisition. Group allocations were decoded afterwards for the purpose of data analysis. The institutional review boards of Anhui Medical University approved the study (20200770). Written informed consent was obtained from each lung cancer patient.

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Guo, L., Xia, Y., Li, H. et al. FIT links c-Myc and P53 acetylation by recruiting RBBP7 during colorectal carcinogenesis. Cancer Gene Ther 30, 1124–1133 (2023). https://doi.org/10.1038/s41417-023-00624-z

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