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解析PRKCI及关键癌症相关基因在乳腺癌发生和转移中的作用。

Unravelling the role of PRKCI and key-cancer related genes in breast cancer development and metastasis.

作者信息

Shah Hania, Khan Khushbukhat, Badshah Yasmin, Trembley Janeen H, Ashraf Naeem Mahmood, Shabbir Maria, Afsar Tayyaba, Aldisi Dara, Khan Dilawer, Razak Suhail

机构信息

Department of Healthcare Biotechnology, Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.

Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.

出版信息

Discov Oncol. 2025 Mar 18;16(1):350. doi: 10.1007/s12672-025-02133-x.

DOI:10.1007/s12672-025-02133-x
PMID:40100546
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11920535/
Abstract

BACKGROUND

Breast cancer is one of the most common causes of fatalities in females globally. Rising cases of drug resistance against existing chemotherapeutics are great problem. To address this issue, there is a need to find appropriate biomarker that could be used to detect cancer at early stages, so drug resistance development can be avoided. Protein Kinase C iota (PKCɩ), an AGC kinase, has an oncogenic role in cancers and its expression and Single nucleotide polymorphisms (SNPs) have been reported to be associated with the cancer development. So, the study aims were to examine the expression of PKCɩ, Protein Kinase B (AKT), Suppressor of cytokine signaling 3 (SOCS3), Vascular endothelial growth factor (VEGF), Krupple like factor 3 (KLF3), Tumor protein D52 (TPD52), Hypoxia inducible factor (HIF1α) and microRNA-124 (miR-124) in breast cancer and association of PKCɩ variants (G34W & F66Y) with breast cancer.

METHODS

Genetic expression assay was performed through real time Polymerase Chain reaction (PCR), whereas the genotypic association of PKCɩ SNPs with breast cancer was accomplished through Tetra-ARMS PCR.

RESULTS

The expression levels of PKCɩ, AKT, SOC3, VEGF, HIF1α and TPD52 were elevated in patients as compared to control whereas the expression levels of miR-124 and KLF3 were lowered in patients. Positive association of variant G34W (TT) of PKCɩ with breast cancer has been explored through ARM's PCR, while no association of variant F66Y with breast cancer was found.

CONCLUSION

Hence, the results suggest that PKCɩ and related genes can have a role in breast cancer and after further verification can serve as the potential biomarkers for the early-diagnosis and prognosis of breast cancer.

摘要

背景

乳腺癌是全球女性死亡的最常见原因之一。对现有化疗药物耐药性病例的增加是一个重大问题。为解决这一问题,需要找到合适的生物标志物,用于在早期检测癌症,从而避免耐药性的发展。蛋白激酶Cι(PKCι)是一种AGC激酶,在癌症中具有致癌作用,其表达和单核苷酸多态性(SNP)据报道与癌症发展相关。因此,本研究旨在检测蛋白激酶Cι(PKCι)、蛋白激酶B(AKT)、细胞因子信号转导抑制因子3(SOCS3)、血管内皮生长因子(VEGF)、类 Krupple 因子3(KLF3)、肿瘤蛋白D52(TPD52)、缺氧诱导因子(HIF1α)和微小RNA-124(miR-124)在乳腺癌中的表达情况,以及PKCι变体(G34W和F66Y)与乳腺癌的关联。

方法

通过实时聚合酶链反应(PCR)进行基因表达检测,而PKCι单核苷酸多态性与乳腺癌的基因型关联则通过四引物扩增受阻突变体系PCR完成。

结果

与对照组相比,患者中PKCι、AKT、SOC3、VEGF、HIF1α和TPD52的表达水平升高,而miR-124和KLF(3)的表达水平降低。通过扩增受阻突变体系PCR研究发现PKCι变体G34W(TT)与乳腺癌呈正相关,而未发现变体F66Y与乳腺癌有关联。

结论

因此,结果表明PKCι和相关基因可能在乳腺癌中起作用,经进一步验证后可作为乳腺癌早期诊断和预后的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/e827e8ce61ca/12672_2025_2133_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/676676264f7b/12672_2025_2133_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/1d761962f694/12672_2025_2133_Fig5_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/2c4bca8e3488/12672_2025_2133_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/e827e8ce61ca/12672_2025_2133_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/676676264f7b/12672_2025_2133_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/f08ad903b939/12672_2025_2133_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/e991a0cd1209/12672_2025_2133_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/b6f6ead5c03c/12672_2025_2133_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/1d761962f694/12672_2025_2133_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/36e6e630b1f0/12672_2025_2133_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/d1cbe053051b/12672_2025_2133_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/2c4bca8e3488/12672_2025_2133_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a95/11920535/e827e8ce61ca/12672_2025_2133_Fig9_HTML.jpg

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