Upregulation of KIN17 is associated with non-small cell lung cancer invasiveness

Zhang, Yuzhao; Huang, Suming; Gao, Hong-Yi; K, Wu; Ouyang, Xiaoming; Zhu, Zheng; Yu, Xiaofeng; Zeng, Tao

doi:10.3892/ol.2017.5707

Cited by 15 publications

(16 citation statements)

References 21 publications

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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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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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“…Although the KIN17 protein serves an important role in human cells, it is not a highly expressed protein in all human tissues. Normally, KIN17 expression in the majority of normal tissues is low, while KIN17 upregulation has been detected in various cancer tissues ( 27 ), such as breast cancer ( 16 ), cervical cancer ( 17 ), liver cancer ( 18 ) and lung cancer ( 19 ). Compared with the normal breast cell line HS578Bst, the expression levels of KIN17 are upregulated in MDA-MB-231, SKBr-3, BT474, and MCF-7 cell lines (breast carcinoma) ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

“…Migration of EOC cells is markedly related to the prognosis of patients ( 34 ). A previous study suggested that KIN17 might be a prognostic biomarker of non-small cell lung cancer (NSCLC), since it serves a key role in the invasion and metastasis of NSCLC cells ( 19 ). The effect of KIN17 on cell invasion has also been observed in cervical cancer ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

“…Proliferation, invasion and metastasis are inhibited by downregulation of the KIN17 protein, thereby inducing apoptosis and cell cycle arrest in cervical cancer cells ( 17 ). The KIN17 protein can induce the proliferation of liver cancer cells ( 18 ), and its upregulation is associated with the invasion and metastasis of non-small cell lung cancer ( 19 ). However, to the best of our knowledge, the effect of KIN17 in ovarian cancer remains unclear and requires further exploration.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of the association between KIN17 expression and the clinical features/prognosis of epithelial ovarian cancer, and the effects of KIN17 in SKOV3 cells

et al. 2021

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DNA double-strand breaks (DSBs) are an important mechanism of chemotherapy in epithelial ovarian cancer (EOC). Kin17 DNA and RNA binding protein (KIN17) serves a crucial role in DSB repair. In the present study, the association between KIN17 and EOC, and the effects of KIN17 on EOC cells in vitro were evaluated. A bioinformatics method was used to determine the mRNA expression levels of KIN17 in EOC and its association with EOC prognosis including overall survival (OS) and progression free survival (PFS) time. Western blotting and immunohistochemical staining were used to evaluate the expression levels of KIN17 in EOC samples. Kaplan-Meier and Cox regression analyses were utilized to analyze risk factors for the OS of patients with EOC. A Cell Counting Kit-8 assay was performed to explore the roles of KIN17 in SKOV3 cells. Both the transcription and expression of KIN17 were upregulated in EOC tissues. Furthermore, the OS of patients with EOC with high mRNA expression levels of KIN17 was shorter than that of patients with EOC with low expression levels. High KIN17 expression was an independent risk factor for EOC prognosis. Furthermore, KIN17 knockdown inhibited the proliferation of SKOV3 cells, enhanced the sensitivity of the cells to cisplatin and inhibited the migration ability of the cells. These results suggested that KIN17 may act as an ideal candidate for therapy and as a prognostic biomarker of EOC, although the underlying mechanisms require further exploration.

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“…Studies of KIN in human colorectal cancer cells, using siRNA to silence its expression, indicated reduced cell proliferation and an accumulation of cells in the beginning or middle of cell cycle S phase [5]. KIN is overexpressed in most cancer cells studied so far [1,6,7], except for the cell line derived from MeWo melanoma [8].…”

Section: Introductionmentioning

confidence: 99%

Interactome Analysis of KIN (Kin17) Shows New Functions of This Protein

Gaspar

Ramos

Cloutier

et al. 2021

CIMB

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KIN (Kin17) protein is overexpressed in a number of cancerous cell lines, and is therefore considered a possible cancer biomarker. It is a well-conserved protein across eukaryotes and is ubiquitously expressed in all cell types studied, suggesting an important role in the maintenance of basic cellular function which is yet to be well determined. Early studies on KIN suggested that this nuclear protein plays a role in cellular mechanisms such as DNA replication and/or repair; however, its association with chromatin depends on its methylation state. In order to provide a better understanding of the cellular role of this protein, we investigated its interactome by proximity-dependent biotin identification coupled to mass spectrometry (BioID-MS), used for identification of protein–protein interactions. Our analyses detected interaction with a novel set of proteins and reinforced previous observations linking KIN to factors involved in RNA processing, notably pre-mRNA splicing and ribosome biogenesis. However, little evidence supports that this protein is directly coupled to DNA replication and/or repair processes, as previously suggested. Furthermore, a novel interaction was observed with PRMT7 (protein arginine methyltransferase 7) and we demonstrated that KIN is modified by this enzyme. This interactome analysis indicates that KIN is associated with several cell metabolism functions, and shows for the first time an association with ribosome biogenesis, suggesting that KIN is likely a moonlight protein.

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Upregulation of KIN17 is associated with non-small cell lung cancer invasiveness

Cited by 15 publications

References 21 publications

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

Analysis of the association between KIN17 expression and the clinical features/prognosis of epithelial ovarian cancer, and the effects of KIN17 in SKOV3 cells

Interactome Analysis of KIN (Kin17) Shows New Functions of This Protein

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