Knockdown of DNA/RNA‑binding protein KIN17 promotes apoptosis of triple‑negative breast cancer cells

Gao, Xiang; Liu, Zhenping; Zhong, Meifeng; K, Wu; Zhang, Yuzhao; Wang, Hongmei; Zeng, Tao

doi:10.3892/ol.2018.9597

Cited by 14 publications

(18 citation statements)

References 25 publications

(26 reference statements)

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“…In breast cancer, KIN17 is associated with apoptosis. Depletion of KIN17 was associated with reduced cell proliferation and increased activity of Caspase 3/7, which promotes apoptosis [ 163 ]. The RBM family member, RBM10, is associated with apoptosis through its ability to regulate the levels of p53 and cleaved PARP [ 164 ].…”

Section: Implications Of Rbps In Cancer Phenotypesmentioning

confidence: 99%

RNA-Binding Proteins in Cancer: Functional and Therapeutic Perspectives

Kang

Lee

2020

Cancers

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RNA-binding proteins (RBPs) crucially regulate gene expression through post-transcriptional regulation, such as by modulating microRNA (miRNA) processing and the alternative splicing, alternative polyadenylation, subcellular localization, stability, and translation of RNAs. More than 1500 RBPs have been identified to date, and many of them are known to be deregulated in cancer. Alterations in the expression and localization of RBPs can influence the expression levels of oncogenes, tumor-suppressor genes, and genome stability-related genes. RBP-mediated gene regulation can lead to diverse cancer-related cellular phenotypes, such as proliferation, apoptosis, angiogenesis, senescence, and epithelial-mesenchymal transition (EMT)/invasion/metastasis. This regulation can also be associated with cancer prognosis. Thus, RBPs can be potential targets for the development of therapeutics for the cancer treatment. In this review, we describe the molecular functions of RBPs, their roles in cancer-related cellular phenotypes, and various approaches that may be used to target RBPs for cancer treatment.

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Section: Implications Of Rbps In Cancer Phenotypesmentioning

confidence: 99%

RNA-Binding Proteins in Cancer: Functional and Therapeutic Perspectives

Kang

Lee

2020

Cancers

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“…Conditional grayscale shading highlights patterns in numerical data. KIN17 was first identified in a search for mammalian homologs of the bacterial DNA repair protein RecA, and has since been studied primarily for roles in DNA damage repair and transcription in eukaryotic cells [27][28][29][30][31][32][33][34][35][36][37] or cancer [38,39] . In S. cerevisiae , there is a named gene, RTS2, that shares homology with the N-terminal portion of KIN17 [40] .…”

Section: Resultsmentioning

confidence: 99%

A Genetic Screen for Suppressors of Cryptic 5’ Splicing inC. elegansReveals Roles for KIN17 and PRCC in Maintaining Both 5’ and 3’ Splice Site Identity

Jm¹,

Osterhoudt²,

Ch³

et al. 2021

Preprint

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Pre-mRNA splicing is an essential step of eukaryotic gene expression carried out by a series of dynamic macromolecular protein/RNA complexes, known collectively and individually as the spliceosome. This series of spliceosomal complexes define, assemble on, and catalyze the removal of introns. Molecular model snapshots of intermediates in the process have been created from cryo-EM data, however, many aspects of the dynamic changes that occur in the spliceosome are not fully understood. Caenorhabditis elegans follow the GU-AG rule of splicing, with almost all introns beginning with 5′ GU and ending with 3′ AG. These splice sites are identified early in the splicing cycle, but as the cycle progresses and ″custody″ of the pre-mRNA splice sites is passed from factor to factor as the catalytic site is built, the mechanism by which splice site identity is maintained or re-established through these dynamic changes is unclear. We performed a genetic screen in C. elegans for factors that are capable of changing 5′ splice site choice. We report that KIN17 and PRCC are involved in splice site choice, the first functional splicing role proposed for either of these proteins. Previously identified suppressors of cryptic 5′ splicing promote distal cryptic GU splice sites, however, mutations in KIN17 and PRCC instead promote usage of an unusual proximal 5′ splice site which defines an intron beginning with UU, separated by 1nt from a GU donor. We performed high-throughput mRNA sequencing analysis and found that mutations in PRCC but not KIN17 changed 5′ splice sites genome-wide, promoting usage of nearby non-consensus sites. We further found that mutations in KIN17 and PRCC changed dozens of 3′ splice sites, promoting non-consensus sites upstream of canonical splice sites. Our work has uncovered both fine and coarse mechanisms by which the spliceosome maintains splice site identity during the complex assembly process.

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“…There are mutations in key spliceosomal proteins such as SF3b1 and SR proteins, that are associated with cancer progression [70][71][72]. KIN17 upregulation has been shown to increase proliferation of lung and breast cancers [38,73] and knockdown of KIN17 reduces cell growth and increases cancer apoptosis [37]. Given the categorization of KIN17 as a DNA damage repair protein, these effects of KIN17 on cancer have been taken as evidence that KIN17 promotes genome stability.…”

Section: Discussionmentioning

confidence: 99%

“…KIN17 was first identified in a search for mammalian homologs of the bacterial DNA repair protein RecA and has since been studied primarily for roles in DNA damage repair and transcription in eukaryotic cells [26][27][28][29][30][31][32][33][34][35][36] or cancer [37,38]. In S. cerevisiae, there is a named gene, RTS2, that shares homology with the N-terminal portion of KIN17 [39].…”

Section: The Four New Type III Suppressor Alleles Are In the C Elegan...mentioning

confidence: 99%

A genetic screen in C. elegans reveals roles for KIN17 and PRCC in maintaining 5’ splice site identity

et al. 2022

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Pre-mRNA splicing is an essential step of eukaryotic gene expression carried out by a series of dynamic macromolecular protein/RNA complexes, known collectively and individually as the spliceosome. This series of spliceosomal complexes define, assemble on, and catalyze the removal of introns. Molecular model snapshots of intermediates in the process have been created from cryo-EM data, however, many aspects of the dynamic changes that occur in the spliceosome are not fully understood. Caenorhabditis elegans follow the GU-AG rule of splicing, with almost all introns beginning with 5’ GU and ending with 3’ AG. These splice sites are identified early in the splicing cycle, but as the cycle progresses and “custody” of the pre-mRNA splice sites is passed from factor to factor as the catalytic site is built, the mechanism by which splice site identity is maintained or re-established through these dynamic changes is unclear. We performed a genetic screen in C. elegans for factors that are capable of changing 5’ splice site choice. We report that KIN17 and PRCC are involved in splice site choice, the first functional splicing role proposed for either of these proteins. Previously identified suppressors of cryptic 5’ splicing promote distal cryptic GU splice sites, however, mutations in KIN17 and PRCC instead promote usage of an unusual proximal 5’ splice site which defines an intron beginning with UU, separated by 1nt from a GU donor. We performed high-throughput mRNA sequencing analysis and found that mutations in PRCC, and to a lesser extent KIN17, changed alternative 5’ splice site usage at native sites genome-wide, often promoting usage of nearby non-consensus sites. Our work has uncovered both fine and coarse mechanisms by which the spliceosome maintains splice site identity during the complex assembly process.

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Knockdown of DNA/RNA‑binding protein KIN17 promotes apoptosis of triple‑negative breast cancer cells

Cited by 14 publications

References 25 publications

RNA-Binding Proteins in Cancer: Functional and Therapeutic Perspectives

RNA-Binding Proteins in Cancer: Functional and Therapeutic Perspectives

A Genetic Screen for Suppressors of Cryptic 5’ Splicing inC. elegansReveals Roles for KIN17 and PRCC in Maintaining Both 5’ and 3’ Splice Site Identity

A genetic screen in C. elegans reveals roles for KIN17 and PRCC in maintaining 5’ splice site identity

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