Possible prognostic impact of PKCι genetic variants in prostate cancer

被引：0

作者：

Hafeez, Amna ^{[1
]}

Shabbir, Maria ^{[1
]}

Khan, Khushbukhat ^{[1
]}

Trembley, Janeen H. ^{[2
,3
,4
]}

Badshah, Yasmin ^{[1
]}

Zafar, Sameen ^{[1
]}

Shahid, Kanza ^{[1
]}

Shah, Hania ^{[1
]}

Ashraf, Naeem Mahmood ^{[5
]}

Hamid, Arslan ^{[6
]}

Afsar, Tayyaba ^{[7
]}

Almajwal, Ali ^{[7
]}

Marium, Afifa ^{[1
]}

Razak, Suhail ^{[7
]}

机构：

[1] Natl Univ Sci & Technol, Rahman Sch Appl Biosci, Dept Healthcare Biotechnol, Islamabad, Pakistan

[2] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN USA

[3] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA

[4] Minneapolis VA Hlth Care Syst Res Serv, Minneapolis, MN USA

[5] Univ Gujrat, Dept Biochem & Biotechnol, Hafiz Hayat Campus, Gujrat 50700, Punjab, Pakistan

[6] Univ Bonn, LIMES Inst AG Netea, Carl Troll Str 31, D-53115 Bonn, Germany

[7] King Saud Univ, Coll Appl Med Sci, Dept Community Hlth Sci, Riyadh, Saudi Arabia

来源：

CANCER CELL INTERNATIONAL | 2024年 / 24卷 / 01期

关键词：

PKC iota; Prostate cancer; Pathways; Molecular dynamic simulations; PROTEIN-KINASE-C; MESSENGER-RNA STRUCTURE; CRYSTAL-STRUCTURE; ATYPICAL PKCS; CELL; DYNAMICS; DOMAIN; FLEXIBILITY; ADAPTATION;

D O I：

10.1186/s12935-023-03182-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Single nucleotide polymorphisms (SNPs) have been linked with prostate cancer (PCa) and have shown potential as prognostic markers for advanced stages. Loss of function mutations in PKC iota have been linked with increased risk of malignancy by enhancing tumor cell motility and invasion. We have evaluated the impact of two coding region SNPs on the PKC iota gene (PRKCI) and their prognostic potential.Methods Genotypic association of non-synonymous PKC iota SNPs rs1197750201 and rs1199520604 with PCa was determined through tetra-ARMS PCR. PKC iota was docked with interacting partner Par-6 to determine the effect of these variants on PKC iota binding capabilities. Molecular dynamic simulations of PKC iota docked with Par-6 were performed to determine variant effects on PKC iota protein interactions. The possible impact of changes in PKC iota protein interactions on epithelial cell polarity was hypothesized.Results PKC iota rs1199520604 mutant genotype TT showed association with PCa (p = 0.0055), while rs1197750201 mutant genotype AA also showed significant association with PCa (P = 0.0006). The binding interaction of PKC iota with Par-6 was altered for both variants, with changes in Van der Waals energy and electrostatic energy of docked structures.Conclusion Genotypic analysis of two non-synonymous PKC iota variants in association with PCa prognosis was performed. Both variants in the PB1 domain showed potential as a prognostic marker for PCa. In silico analysis of the effect of the variants on PKC iota protein interactions indicated they may be involved in PCa progression through aberration of epithelial cell polarity pathways.

引用

页数：12

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