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Protein co-expression network-based profiles revealed from laser-microdissected cancerous cells of lung squamous-cell carcinomas

Nishimura, Toshihide ; Fujii, Kiyonaga ; Nakamura, Haruhiko ; Naruki, Saeko ; Sakai, Hiroki ; Kimura, Hiroyuki ; Miyazawa, Tomoyuki ; Takagi, Masayuki ; Furuya, Naoki and Marko-Varga, Gyorgy LU , et al. (2021) In Scientific Reports 11(1).
Abstract

No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to unveil disease-related protein networks by proteomic and bioinformatic assessment of laser-microdissected cancerous cells from seven SqCCs compared with eight representative lung adenocarcinomas. We identified three network modules significant to lung SqCC using weighted gene co-expression network analysis. One module was intrinsically annotated to keratinization and cell proliferation of SqCC, accompanied by hypoxia-induced aerobic glycolysis, in which key regulators were activated (HIF1A, ROCK2, EFNA1-5) and highly suppressed (KMT2D). The... (More)

No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to unveil disease-related protein networks by proteomic and bioinformatic assessment of laser-microdissected cancerous cells from seven SqCCs compared with eight representative lung adenocarcinomas. We identified three network modules significant to lung SqCC using weighted gene co-expression network analysis. One module was intrinsically annotated to keratinization and cell proliferation of SqCC, accompanied by hypoxia-induced aerobic glycolysis, in which key regulators were activated (HIF1A, ROCK2, EFNA1-5) and highly suppressed (KMT2D). The other two modules were significant for translational initiation, nonsense-mediated mRNA decay, inhibited cell death, and interestingly, eIF2 signaling, in which key regulators, MYC and MLXIPL, were highly activated. Another key regulator LARP1, the master regulator in cap-dependent translation, was highly suppressed although upregulations were observed for hub proteins including EIF3F and LARP1 targeted ribosomal proteins, among which PS25 is the key ribosomal protein in IRES-dependent translation. Our results suggest an underlying progression mechanism largely caused by switching to the cap-independent, IRES-dependent translation of mRNA subsets encoding oncogenic proteins. Our findings may help to develop therapeutic strategies to improve patient outcomes.

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type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
11
issue
1
article number
20209
publisher
Nature Publishing Group
external identifiers
  • pmid:34642392
  • scopus:85117415262
ISSN
2045-2322
DOI
10.1038/s41598-021-99695-x
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021, The Author(s).
id
f675c13d-cc22-4b41-92db-ff9cbdbde94b
date added to LUP
2021-11-19 12:54:51
date last changed
2025-03-09 22:12:36
@article{f675c13d-cc22-4b41-92db-ff9cbdbde94b,
  abstract     = {{<p>No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to unveil disease-related protein networks by proteomic and bioinformatic assessment of laser-microdissected cancerous cells from seven SqCCs compared with eight representative lung adenocarcinomas. We identified three network modules significant to lung SqCC using weighted gene co-expression network analysis. One module was intrinsically annotated to keratinization and cell proliferation of SqCC, accompanied by hypoxia-induced aerobic glycolysis, in which key regulators were activated (HIF1A, ROCK2, EFNA1-5) and highly suppressed (KMT2D). The other two modules were significant for translational initiation, nonsense-mediated mRNA decay, inhibited cell death, and interestingly, eIF2 signaling, in which key regulators, MYC and MLXIPL, were highly activated. Another key regulator LARP1, the master regulator in cap-dependent translation, was highly suppressed although upregulations were observed for hub proteins including EIF3F and LARP1 targeted ribosomal proteins, among which PS25 is the key ribosomal protein in IRES-dependent translation. Our results suggest an underlying progression mechanism largely caused by switching to the cap-independent, IRES-dependent translation of mRNA subsets encoding oncogenic proteins. Our findings may help to develop therapeutic strategies to improve patient outcomes.</p>}},
  author       = {{Nishimura, Toshihide and Fujii, Kiyonaga and Nakamura, Haruhiko and Naruki, Saeko and Sakai, Hiroki and Kimura, Hiroyuki and Miyazawa, Tomoyuki and Takagi, Masayuki and Furuya, Naoki and Marko-Varga, Gyorgy and Kato, Harubumi and Saji, Hisashi}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Protein co-expression network-based profiles revealed from laser-microdissected cancerous cells of lung squamous-cell carcinomas}},
  url          = {{http://dx.doi.org/10.1038/s41598-021-99695-x}},
  doi          = {{10.1038/s41598-021-99695-x}},
  volume       = {{11}},
  year         = {{2021}},
}