SRPKs: a promising therapeutic target in cancer

Tufail, Muhammad; Wu, Changxin

doi:10.1007/s10238-023-01054-9

Cited by 4 publications

(2 citation statements)

References 87 publications

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“…It has been found that RNA interference (RNAi) is a revolutionary technique for modifying gene expressions. The small interfering RNA (siRNA) was loaded into the RNA-induced silencing complex (RISC) effector complex to unwind, where single-stranded RNA hybridizes with mRNA targets, resulting in gene silencing and protein down-regulation (Chen et al 2018;Tufail and Wu 2023;Cömez and Akbuğa 2023).…”

Section: Introductionmentioning

confidence: 99%

Functionalized siRNA-chitosan nanoformulations promote triple-negative breast cancer cell death via blocking the miRNA-21/AKT/ERK signaling axis: in-silico and in vitro studies

Abdulmalek,

Saleh,

Shahin

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Oncogenic microRNA (miRNA), especially miRNA-21 upregulation in triple-negative breast cancer (TNBC), suggests a new class of therapeutic targets. In this study, we aimed to create GE11 peptide-conjugated small interfering RNA-loaded chitosan nanoparticles (GE11-siRNA-CSNPs) for the targeting of EGFR overexpressed TNBC and selectively inhibit miRNA-21 expression. A variety of in-silico and in vitro cellular and molecular studies were conducted to investigate the binding affinities of specific targets used as well as the anticancer efficacies and mechanisms of GE11-siRNA-CSNPs in TNBC cells. An in-silico assessment reveals a distinct binding affinity of miRNA-21 with siRNA as well as between the extracellular domain of EGFR and synthesized peptides. Notably, the in vitro results showed that GE11-siRNA-CSNPs were revealed to have better cytotoxicity against TNBC cells. It significantly inhibits miRNA-21 expression, cell migration, and colony formation. The results also indicated that GE11-siRNA-CSNPs impeded cell cycle progression. It induces cell death by reducing the expression of the antiapoptotic gene Bcl-2 and increasing the expression of the proapoptotic genes Bax, Caspase 3, and Caspase 9. Additionally, the docking analysis and immunoblot investigations verified that GE1-siRNA-CSNPs, which specifically target TNBC cells and suppress miRNA-21, can prevent the effects of miRNA-21 on the proliferation of TNBC cells via controlling EGFR and subsequently inhibiting the PI3K/AKT and ERK1/2 signaling axis. The GE11-siRNA-CSNPs design, which specifically targets TNBC cells, offers a novel approach for the treatment of breast cancer with improved effectiveness. This study suggests that GE11-siRNA-CSNPs could be a promising candidate for further assessment as an additional strategy in the treatment of TNBC. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

Functionalized siRNA-chitosan nanoformulations promote triple-negative breast cancer cell death via blocking the miRNA-21/AKT/ERK signaling axis: in-silico and in vitro studies

Abdulmalek,

Saleh,

Shahin

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Given the pivotal roles of SRPKs in the regulation of SR splicing factors, their dysregulated expression can serve as predictive and prognostic indicators for various cancers 14 – 16 . High expression of SRPK1 or SRPK2 was observed in clinical samples of multiple carcinomas as well as nonepithelial cancers, such as glioblastomas and several forms of leukemia 15 , 17 – 19 .…”

Section: Introductionmentioning

confidence: 99%

Design of a covalent protein-protein interaction inhibitor of SRPKs to suppress angiogenesis and invasion of cancer cells

Cai,

Bao,

et al. 2024

Commun Chem

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Serine–arginine (SR) proteins are splicing factors that play essential roles in both constitutive and alternative pre-mRNA splicing. Phosphorylation of their C-terminal RS domains by SR protein kinases (SRPKs) regulates their localization and diverse cellular activities. Dysregulation of phosphorylation has been implicated in many human diseases, including cancers. Here, we report the development of a covalent protein–protein interaction inhibitor, C-DBS, that targets a lysine residue within the SRPK-specific docking groove to block the interaction and phosphorylation of the prototypic SR protein SRSF1. C-DBS exhibits high specificity and conjugation efficiency both in vitro and in cellulo. This self-cell-penetrating inhibitor attenuates the phosphorylation of endogenous SR proteins and subsequently inhibits the angiogenesis, migration, and invasion of cancer cells. These findings provide a new foundation for the development of covalent SRPK inhibitors for combatting diseases such as cancer and viral infections and overcoming the resistance encountered by ATP-competitive inhibitors.

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Microtubules and cardiovascular diseases: insights into pathology and therapeutic strategies

Wu,

Wang,

Liu

et al. 2024

The International Journal of Biochemistry & Cell Biology

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SRPKs: a promising therapeutic target in cancer

Cited by 4 publications

References 87 publications

Functionalized siRNA-chitosan nanoformulations promote triple-negative breast cancer cell death via blocking the miRNA-21/AKT/ERK signaling axis: in-silico and in vitro studies

Functionalized siRNA-chitosan nanoformulations promote triple-negative breast cancer cell death via blocking the miRNA-21/AKT/ERK signaling axis: in-silico and in vitro studies

Design of a covalent protein-protein interaction inhibitor of SRPKs to suppress angiogenesis and invasion of cancer cells

Microtubules and cardiovascular diseases: insights into pathology and therapeutic strategies

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