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


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.

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Data availability

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


  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  PubMed  Google Scholar 

  2. Fearon ERVB. A genetic model for colorectal tumorigenesis. Cell 1990;61:759–67.

    Article  CAS  PubMed  Google Scholar 

  3. Levine AJ. p53: 800 million years of evolution and 40 years of discovery. Nat Rev Cancer. 2020;20:471–80.

    Article  CAS  PubMed  Google Scholar 

  4. Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, et al. Negative control of p53 by Sir2α promotes cell survival under stress. Cell 2001;107:137–48.

    Article  CAS  PubMed  Google Scholar 

  5. Lill NL, Grossman SR, Ginsberg D, DeCaprio J, Livingston DM. Binding and modulation of p53 by p300/CBP coactivators. Nature. 1997;387:823–7.

    Article  CAS  PubMed  Google Scholar 

  6. Barlev NA, Chehab NH, Mansfield K, Harris KG, Halazonetis TD, Berger SL. Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol Cell. 2001;8:1243–54.

    Article  CAS  PubMed  Google Scholar 

  7. Brasen C, Dorosz J, Wiuf A, Boesen T, Mirza O, Gajhede M. Expression, purification and characterization of the human MTA2-RBBP7 complex. Biochim Biophys Acta Proteins Proteom. 2017;1865:531–8.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang Q, Vo N, Goodman RH. Histone binding protein RbAp48 interacts with a complex of CREB binding protein and phosphorylated CREB. Mol Cell Biol. 2000;20:4970–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Müller MWS, Bannasch D, Israeli D, Lehlbach K, Li-Weber M, Friedman SL, et al. p53 activates the CD95 (APO-1/Fas) gene in response to DNA damage by anticancer drugs. J Exp Med. 1998;188:2033–45.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Strasser A, Jost PJ, Nagata S. The many roles of FAS receptor signaling in the immune system. Immunity 2009;30:180–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Collins S. Amplification of endogenous myc-related DNA sequences in a human myeloid leukaemia cell line. Nature. 1982;298:679–81.

    Article  CAS  PubMed  Google Scholar 

  12. Meyer N. Reflecting on 25 years with MYC. Nat Rev Cancer. 2008;8:976–90.

    Article  CAS  PubMed  Google Scholar 

  13. Dang CV. MYC on the path to cancer. Cell. 2012;149:22–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Eischen CM, Roussel MF, Sherr CJ, Cleveland JL. Disruption of the ARF–Mdm2–p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Genes Dev. 1999;13:2658–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zindy FEC, Randle DH, Kamijo T, Cleveland JL, Sherr CJ, Roussel MF. Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization. Genes Dev. 1998;12:2424–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Feng YC, Liu XY, Teng L, Ji Q, Wu Y, Li JM, et al. c-Myc inactivation of p53 through the pan-cancer lncRNA MILIP drives cancer pathogenesis. Nat Commun. 2020;11:4980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. McCleland ML, Mesh K, Lorenzana E, Chopra VS, Segal E, Watanabe C, et al. CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016;126:639–52.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Chen B, Dragomir MP, Fabris L, Bayraktar R, Knutsen E, Liu X, et al. The long noncoding RNA CCAT2 induces chromosomal instability through BOP1-AURKB signaling. Gastroenterology 2020;159:2146–62 e33.

    Article  CAS  PubMed  Google Scholar 

  19. Ma Y, Yang Y, Wang F, Moyer MP, Wei Q, Zhang P, et al. Long non-coding RNA CCAL regulates colorectal cancer progression by activating Wnt/beta-catenin signalling pathway via suppression of activator protein 2alpha. Gut 2016;65:1494–504.

    Article  CAS  PubMed  Google Scholar 

  20. Xiang S, Gu H, Jin L, Thorne RF, Zhang XD, Wu M. LncRNA IDH1-AS1 links the functions of c-Myc and HIF1alpha via IDH1 to regulate the Warburg effect. Proc Natl Acad Sci USA. 2018;115:E1465–E74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fischer M. Census and evaluation of p53 target genes. Oncogene 2017;36:3943–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Li Q, Wang Y, Wu S, Zhou Z, Ding X, Shi R, et al. CircACC1 regulates assembly and activation of AMPK complex under metabolic stress. Cell Metab. 2019;30:157–73 e7.

    Article  PubMed  Google Scholar 

  23. Du W, Jiang P, Li N, Mei Y, Wang X, Wen L, et al. Suppression of p53 activity by Siva1. Cell Death Differ. 2009;16:1493–504.

    Article  CAS  PubMed  Google Scholar 

  24. Hoogwater FJ, Nijkamp MW, Smakman N, Steller EJ, Emmink BL, Westendorp BF, et al. Oncogenic K-Ras turns death receptors into metastasis-promoting receptors in human and mouse colorectal cancer cells. Gastroenterology 2010;138:2357–67.

    Article  CAS  PubMed  Google Scholar 

  25. Fogeron ML, Muller H, Schade S, Dreher F, Lehmann V, Kuhnel A, et al. LGALS3BP regulates centriole biogenesis and centrosome hypertrophy in cancer cells. Nat Commun. 2013;4:1531.

    Article  PubMed  Google Scholar 

  26. Zhang M, Weng W, Zhang Q, Wu Y, Ni S, Tan C, et al. The lncRNA NEAT1 activates Wnt/beta-catenin signaling and promotes colorectal cancer progression via interacting with DDX5. J Hematol Oncol. 2018;11:113.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ni W, Yao S, Zhou Y, Liu Y, Huang P, Zhou A, et al. Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m(6)A reader YTHDF3. Mol Cancer. 2019;18:143.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lin X, Zhuang S, Chen X, Du J, Zhong L, Ding J, et al. lncRNA ITGB8-AS1 functions as a ceRNA to promote colorectal cancer growth and migration through integrin-mediated focal adhesion signaling. Mol Ther. 2022;30:688–702.

    Article  CAS  PubMed  Google Scholar 

  29. Xu J, Meng Q, Li X, Yang H, Xu J, Gao N, et al. Long noncoding RNA MIR17HG promotes colorectal cancer progression via miR-17-5p. Cancer Res. 2019;79:4882–95.

    Article  CAS  PubMed  Google Scholar 

  30. Wang X, Zhang H, Yin S, Yang Y, Yang H, Yang J, et al. lncRNA-encoded pep-AP attenuates the pentose phosphate pathway and sensitizes colorectal cancer cells to Oxaliplatin. EMBO Rep. 2022;23:e53140.

    Article  CAS  PubMed  Google Scholar 

  31. Ge Q, Jia D, Cen D, Qi Y, Shi C, Li J, et al. Micropeptide ASAP encoded by LINC00467 promotes colorectal cancer progression by directly modulating ATP synthase activity. J Clin Invest. 2021;131:e152911.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wei H, Qu L, Dai S, Li Y, Wang H, Feng Y, et al. Structural insight into the molecular mechanism of p53-mediated mitochondrial apoptosis. Nat Commun. 2021;12:2280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. McKeown MR, Bradner JE. Therapeutic strategies to inhibit MYC. Cold Spring Harb Perspect Med. 2014;4:a014266.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ivanov VN, Bhoumik A, Krasilnikov M, Raz R, Owen-Schaub LB, Levy D, et al. Cooperation between STAT3 and c-Jun suppresses fas transcription. Mol Cell. 2001;7:517–28.

    Article  CAS  PubMed  Google Scholar 

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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 and Affiliations



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.

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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).

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