Multi-omic analysis suggests tumor suppressor genes evolved specific promoter features to optimize cancer resistance

Dan Huang; Xiansong Wang; Yingzhi Liu; Ziheng Huang; Xiaoxu Hu; Wei Hu; Qing Li; Hung Chan; Yidan Zou; Idy H.T. Ho; Yan Wang; Alfred S.L. Cheng; Wei Kang; Ka F. To; Maggie H.T. Wang; Sunny H. Wong; Jun Yu; Tony Gin; Qingpeng Zhang; Zheng Li; Jianxiong Shen; Lin Zhang; Matthew T.V. Chan; Xiaodong Liu; William K.K. Wu

doi:10.1093/bib/bbab040

Multi-omic analysis suggests tumor suppressor genes evolved specific promoter features to optimize cancer resistance

Dan Huang
, Xiansong Wang
, Yingzhi Liu
, Ziheng Huang
, Xiaoxu Hu
, Wei Hu
, Qing Li
, Hung Chan
, Yidan Zou
, Idy H.T. Ho
, Yan Wang
, Alfred S.L. Cheng
, Wei Kang
, Ka F. To
, Maggie H.T. Wang
, Sunny H. Wong
, Jun Yu
, Tony Gin
, Qingpeng Zhang
, Zheng Li

Jianxiong Shen, Lin Zhang, Matthew T.V. Chan^*, Xiaodong Liu^*, William K.K. Wu^*

^*Corresponding author for this work

Department of Data Science

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

8 Citations (Scopus)

Abstract

Tumor suppressor genes (TSGs) exhibit distinct evolutionary features. We speculated that TSG promoters could have evolved specific features that facilitate their tumor-suppressing functions. We found that the promoter CpG dinucleotide frequencies of TSGs are significantly higher than that of non-cancer genes across vertebrate genomes, and positively correlated with gene expression across tissue types. The promoter CpG dinucleotide frequencies of all genes gradually increase with gene age, for which young TSGs have been subject to a stronger evolutionary pressure. Transcription-related features, namely chromatin accessibility, methylation and ZNF263-, SP1-, E2F4- and SP2-binding elements, are associated with gene expression. Moreover, higher promoter CpG dinucleotide frequencies and chromatin accessibility are positively associated with the ability of TSGs to resist downregulation during tumorigenesis. These results were successfully validated with independent datasets. In conclusion, TSGs evolved specific promoter features that optimized cancer resistance through achieving high expression in normal tissues and resistance to downregulation during tumorigenesis.

Original language	English
Pages (from-to)	1–12
Journal	Briefings in Bioinformatics
Volume	22
Issue number	5
Online published	30 Mar 2021
DOIs	https://doi.org/10.1093/bib/bbab040
Publication status	Published - Sept 2021

Bibliographical note

Full text of this publication does not contain sufficient affiliation information. With consent from the author(s) concerned, the Research Unit(s) information for this record is based on the existing academic department affiliation of the author(s).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

promoter evolution
pan-cancer
CpG island
chromatin
methylation

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Huang, D., Wang, X., Liu, Y., Huang, Z., Hu, X., Hu, W., Li, Q., Chan, H., Zou, Y., Ho, I. H. T., Wang, Y., Cheng, A. S. L., Kang, W., To, K. F., Wang, M. H. T., Wong, S. H., Yu, J., Gin, T., Zhang, Q., ... Wu, W. K. K. (2021). Multi-omic analysis suggests tumor suppressor genes evolved specific promoter features to optimize cancer resistance. Briefings in Bioinformatics, 22(5), 1–12. https://doi.org/10.1093/bib/bbab040

@article{a1cb2dd30b1e48639908b178871d55a0,

title = "Multi-omic analysis suggests tumor suppressor genes evolved specific promoter features to optimize cancer resistance",

abstract = "Tumor suppressor genes (TSGs) exhibit distinct evolutionary features. We speculated that TSG promoters could have evolved specific features that facilitate their tumor-suppressing functions. We found that the promoter CpG dinucleotide frequencies of TSGs are significantly higher than that of non-cancer genes across vertebrate genomes, and positively correlated with gene expression across tissue types. The promoter CpG dinucleotide frequencies of all genes gradually increase with gene age, for which young TSGs have been subject to a stronger evolutionary pressure. Transcription-related features, namely chromatin accessibility, methylation and ZNF263-, SP1-, E2F4- and SP2-binding elements, are associated with gene expression. Moreover, higher promoter CpG dinucleotide frequencies and chromatin accessibility are positively associated with the ability of TSGs to resist downregulation during tumorigenesis. These results were successfully validated with independent datasets. In conclusion, TSGs evolved specific promoter features that optimized cancer resistance through achieving high expression in normal tissues and resistance to downregulation during tumorigenesis.",

keywords = "promoter evolution, pan-cancer, CpG island, chromatin, methylation",

author = "Dan Huang and Xiansong Wang and Yingzhi Liu and Ziheng Huang and Xiaoxu Hu and Wei Hu and Qing Li and Hung Chan and Yidan Zou and Ho, \{Idy H.T.\} and Yan Wang and Cheng, \{Alfred S.L.\} and Wei Kang and To, \{Ka F.\} and Wang, \{Maggie H.T.\} and Wong, \{Sunny H.\} and Jun Yu and Tony Gin and Qingpeng Zhang and Zheng Li and Jianxiong Shen and Lin Zhang and Chan, \{Matthew T.V.\} and Xiaodong Liu and Wu, \{William K.K.\}",

note = "Full text of this publication does not contain sufficient affiliation information. With consent from the author(s) concerned, the Research Unit(s) information for this record is based on the existing academic department affiliation of the author(s).",

year = "2021",

month = sep,

doi = "10.1093/bib/bbab040",

language = "English",

volume = "22",

pages = "1–12",

journal = "Briefings in Bioinformatics",

issn = "1467-5463",

publisher = "Oxford University Press",

number = "5",

}

Huang, D, Wang, X, Liu, Y, Huang, Z, Hu, X, Hu, W, Li, Q, Chan, H, Zou, Y, Ho, IHT, Wang, Y, Cheng, ASL, Kang, W, To, KF, Wang, MHT, Wong, SH, Yu, J, Gin, T, Zhang, Q, Li, Z, Shen, J, Zhang, L, Chan, MTV, Liu, X & Wu, WKK 2021, 'Multi-omic analysis suggests tumor suppressor genes evolved specific promoter features to optimize cancer resistance', Briefings in Bioinformatics, vol. 22, no. 5, pp. 1–12. https://doi.org/10.1093/bib/bbab040

TY - JOUR

T1 - Multi-omic analysis suggests tumor suppressor genes evolved specific promoter features to optimize cancer resistance

AU - Huang, Dan

AU - Wang, Xiansong

AU - Liu, Yingzhi

AU - Huang, Ziheng

AU - Hu, Xiaoxu

AU - Hu, Wei

AU - Li, Qing

AU - Chan, Hung

AU - Zou, Yidan

AU - Ho, Idy H.T.

AU - Wang, Yan

AU - Cheng, Alfred S.L.

AU - Kang, Wei

AU - To, Ka F.

AU - Wang, Maggie H.T.

AU - Wong, Sunny H.

AU - Yu, Jun

AU - Gin, Tony

AU - Zhang, Qingpeng

AU - Li, Zheng

AU - Shen, Jianxiong

AU - Zhang, Lin

AU - Chan, Matthew T.V.

AU - Liu, Xiaodong

AU - Wu, William K.K.

N1 - Full text of this publication does not contain sufficient affiliation information. With consent from the author(s) concerned, the Research Unit(s) information for this record is based on the existing academic department affiliation of the author(s).

PY - 2021/9

Y1 - 2021/9

N2 - Tumor suppressor genes (TSGs) exhibit distinct evolutionary features. We speculated that TSG promoters could have evolved specific features that facilitate their tumor-suppressing functions. We found that the promoter CpG dinucleotide frequencies of TSGs are significantly higher than that of non-cancer genes across vertebrate genomes, and positively correlated with gene expression across tissue types. The promoter CpG dinucleotide frequencies of all genes gradually increase with gene age, for which young TSGs have been subject to a stronger evolutionary pressure. Transcription-related features, namely chromatin accessibility, methylation and ZNF263-, SP1-, E2F4- and SP2-binding elements, are associated with gene expression. Moreover, higher promoter CpG dinucleotide frequencies and chromatin accessibility are positively associated with the ability of TSGs to resist downregulation during tumorigenesis. These results were successfully validated with independent datasets. In conclusion, TSGs evolved specific promoter features that optimized cancer resistance through achieving high expression in normal tissues and resistance to downregulation during tumorigenesis.

AB - Tumor suppressor genes (TSGs) exhibit distinct evolutionary features. We speculated that TSG promoters could have evolved specific features that facilitate their tumor-suppressing functions. We found that the promoter CpG dinucleotide frequencies of TSGs are significantly higher than that of non-cancer genes across vertebrate genomes, and positively correlated with gene expression across tissue types. The promoter CpG dinucleotide frequencies of all genes gradually increase with gene age, for which young TSGs have been subject to a stronger evolutionary pressure. Transcription-related features, namely chromatin accessibility, methylation and ZNF263-, SP1-, E2F4- and SP2-binding elements, are associated with gene expression. Moreover, higher promoter CpG dinucleotide frequencies and chromatin accessibility are positively associated with the ability of TSGs to resist downregulation during tumorigenesis. These results were successfully validated with independent datasets. In conclusion, TSGs evolved specific promoter features that optimized cancer resistance through achieving high expression in normal tissues and resistance to downregulation during tumorigenesis.

KW - promoter evolution

KW - pan-cancer

KW - CpG island

KW - chromatin

KW - methylation

UR - https://www.scopus.com/pages/publications/85116172737

UR - https://www.scopus.com/pages/publications/85116172737#tab=impact

U2 - 10.1093/bib/bbab040

DO - 10.1093/bib/bbab040

M3 - RGC 21 - Publication in refereed journal

C2 - 33783485

SN - 1467-5463

VL - 22

SP - 1

EP - 12

JO - Briefings in Bioinformatics

JF - Briefings in Bioinformatics

IS - 5

ER -

Multi-omic analysis suggests tumor suppressor genes evolved specific promoter features to optimize cancer resistance

Abstract

Bibliographical note

UN SDGs

Research Keywords

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