Reply to: Transformation of naked mole-rat cells

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Fig. 1: Differential response of NMR cells to HRAS(G12V) expression.
Fig. 2: HRAS(G12V) expression levels determine oncogenic transformation in NMR cells.

Data availability

The RNA-seq data have been deposited in the NCBI Sequence Read Archive (SRA) (SRP133455). Uncropped western blots are provided as Supplementary Fig. 1. All other data that support the findings of this study can be found as in bioRxiv preprint11 or are available from the corresponding authors upon reasonable request.

Code availability

Source code are available upon request.


  1. 1.

    Tian, X. et al. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature 499, 346–349 (2013).

    ADS  CAS  Article  Google Scholar 

  2. 2.

    Liang, S., Mele, J., Wu, Y., Buffenstein, R. & Hornsby, P. J. Resistance to experimental tumorigenesis in cells of a long-lived mammal, the naked mole-rat (Heterocephalus glaber). Aging Cell 9, 626–635 (2010).

    CAS  Article  Google Scholar 

  3. 3.

    Hadi, F. et al. Transformation of naked mole-rat cells. Nature (2020).

  4. 4.

    Hahn, W. C. et al. Enumeration of the simian virus 40 early region elements necessary for human cell transformation. Mol. Cell. Biol. 22, 2111–2123 (2002).

    CAS  Article  Google Scholar 

  5. 5.

    Rangarajan, A., Hong, S. J., Gifford, A. & Weinberg, R. A. Species- and cell type-specific requirements for cellular transformation. Cancer Cell 6, 171–183 (2004).

    CAS  Article  Google Scholar 

  6. 6.

    Zhao, J. J. et al. Human mammary epithelial cell transformation through the activation of phosphatidylinositol 3-kinase. Cancer Cell 3, 483–495 (2003).

    CAS  Article  Google Scholar 

  7. 7.

    Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D. & Lowe, S. W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593–602 (1997).

    CAS  Article  Google Scholar 

  8. 8.

    Tian, X. et al. Evolution of telomere maintenance and tumour suppressor mechanisms across mammals. Phil. Trans. R. Soc. Lond. B 373, 20160443 (2018).

    Article  Google Scholar 

  9. 9.

    Elenbaas, B. et al. Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells. Genes Dev. 15, 50–65 (2001).

    CAS  Article  Google Scholar 

  10. 10.

    Hahn, W. C. et al. Creation of human tumour cells with defined genetic elements. Nature 400, 464–468 (1999).

    ADS  CAS  Article  Google Scholar 

  11. 11.

    Zhao, J. et al. Dampened PI3K/AKT signaling contributes to cancer resistance of the naked mole rat. Preprint at bioRxiv (2020).

  12. 12.

    Ayyadevara, S., Alla, R., Thaden, J. J. & Shmookler Reis, R. J. Remarkable longevity and stress resistance of nematode PI3K-null mutants. Aging Cell 7, 13–22 (2008).

    CAS  Article  Google Scholar 

  13. 13.

    Moskalev, A. A. & Shaposhnikov, M. V. Pharmacological inhibition of phosphoinositide 3 and TOR kinases improves survival of Drosophila melanogaster. Rejuvenation Res. 13, 246–247 (2010).

    CAS  Article  Google Scholar 

  14. 14.

    Nojima, A. et al. Haploinsufficiency of Akt1 prolongs the lifespan of mice. PLoS One 8, e69178 (2013).

    ADS  CAS  Article  Google Scholar 

  15. 15.

    Foukas, L. C. et al. Long-term p110α PI3K inactivation exerts a beneficial effect on metabolism. EMBO Mol. Med. 5, 563–571 (2013).

    CAS  Article  Google Scholar 

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This study is supported by US National Institutes of Health grant AG047200 to V.G. and A.S., and Natural Science Foundation of China grant 81672818, Science Technology and Innovation Committee of Shenzhen Municipality grant JCYJ20160331190123578 and Guangzhou Science and Technology Program key project 201604020005 to X.F.

Author information




The list of authors is different from the original study, because new data were included in this Reply. J.Z., X.T., Y.Z., X.F. and V.G. designed research. X.T., Z.Z. and E.R. generated the stable cell lines and performed western blot and xenograft experiments. H.Z. constructed libraries and sequenced the samples. J.Z., Y.Z., Y.Y., B.R., A.C., X.S. and R.H. performed data control and bioinformatics analysis. E.N. provided samples. K.K. contributed to the result interpretation and paper writing. A.S., X.F., and V.G. supervised the study. J.Z., X.T., Y.Z., A.S., X.F. and V.G. wrote the paper with input from all authors.

Corresponding authors

Correspondence to Andrei Seluanov or Xiaodong Fang or Vera Gorbunova.

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The authors declare no competing interests.

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Extended data figures and tables

Extended Data Fig. 1 Tumorigenicity of the cell lines and PCA of the RNA-seq datasets.

a, Tumorigenicity of the cell lines. Cells not analysed in this study are indicated with a ‘-’. All transforming genes were driven by a retroviral LTR promoter. be, PCA of the RNA-seq datasets. PCA was done using the expression of 13,276 orthologous genes across all four species (mouse (b), blind mole rat (c), NMR (d) and human (e)). The first two principal components of each analysis were extracted. Values in parentheses indicate the variance explained by each of the principal components. L, SV40LT; R, HRAS(G12V); T, human TERT. All transgenes are driven by LTR promoters.

Extended Data Fig. 2 Enrichment analysis of DEGs in the transformed cells across species.

a, GO enrichment analysis of the DEGs derived from Fig. 1a. b, GO enrichment analysis of the DEGs derived from Fig. 1b. c, GO enrichment analysis of the DEGs derived from Fig. 1c. Biological process and molecular function terms are shown. All GO terms in ac are arranged in the order of decreasing significance in the mouse cells. The top 20 significantly upregulated (red) and downregulated (green) terms are shown. LT, SV40LT; RAS, HRAS(G12V). All transgenes are driven by LTR promoters.

Extended Data Table 1 Statistics for RNA-seq data and expressed genes for all samples

Supplementary information

Supplementary Information

This file contains Supplementary Methods and Supplementary Figure 1 showing uncropped Western blot images.

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Zhao, J., Tian, X., Zhu, Y. et al. Reply to: Transformation of naked mole-rat cells. Nature 583, E8–E13 (2020).

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