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Genetic screening for anticancer genes highlights FBLN5 as a synthetic lethal partner of MYC.
Masood, Motasim; Ding, Qize; Cawte, Adam D; Rueda, David S; Grimm, Stefan W; Yagüe, Ernesto; El-Bahrawy, Mona.
Afiliação
  • Masood M; Faculty of Medicine, Imperial College London, Du Cane Rd, London, UK.
  • Ding Q; Department of Medicine, Faculty of Medicine, Imperial College London, Du Cane Rd, London, UK.
  • Cawte AD; Single Molecule Imaging Group, MRC London Institute of Medical Sciences, Du Cane Rd, London, UK.
  • Rueda DS; Department of Infectious Disease, Faculty of Medicine, Imperial College London, Du Cane Rd, London, UK.
  • Grimm SW; Single Molecule Imaging Group, MRC London Institute of Medical Sciences, Du Cane Rd, London, UK.
  • Yagüe E; Department of Infectious Disease, Faculty of Medicine, Imperial College London, Du Cane Rd, London, UK.
  • El-Bahrawy M; Department of Medicine, Faculty of Medicine, Imperial College London, Du Cane Rd, London, UK.
Cell Commun Signal ; 21(1): 295, 2023 10 20.
Article em En | MEDLINE | ID: mdl-37864183
ABSTRACT

BACKGROUND:

When ectopically overexpressed, anticancer genes, such as TRAIL, PAR4 and ORCTL3, specifically destroy tumour cells without harming untransformed cells. Anticancer genes can not only serve as powerful tumour specific therapy tools but studying their mode of action can reveal mechanisms underlying the neoplastic transformation, sustenance and spread.

METHODS:

Anticancer gene discovery is normally accidental. Here we describe a systematic, gain of function, forward genetic screen in mammalian cells to isolate novel anticancer genes of human origin. Continuing with over 30,000 transcripts from our previous study, 377 cell death inducing genes were subjected to screening. FBLN5 was chosen, as a proof of principle, for mechanistic gene expression profiling, comparison pathways analyses and functional studies.

RESULTS:

Sixteen novel anticancer genes were isolated; these included non-coding RNAs, protein-coding genes and novel transcripts, such as ZNF436-AS1, SMLR1, TMEFF2, LINC01529, HYAL2, NEIL2, FBLN5, YPEL4 and PHKA2-processed transcript. FBLN5 selectively caused inhibition of MYC in COS-7 (transformed) cells but not in CV-1 (normal) cells. MYC was identified as synthetic lethality partner of FBLN5 where MYC transformed CV-1 cells experienced cell death upon FBLN5 transfection, whereas FBLN5 lost cell death induction in MCF-7 cells upon MYC knockdown.

CONCLUSIONS:

Sixteen novel anticancer genes are present in human genome including FBLN5. MYC is a synthetic lethality partner of FBLN5. Video Abstract.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transformação Celular Neoplásica / Perfilação da Expressão Gênica Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transformação Celular Neoplásica / Perfilação da Expressão Gênica Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article