PLK1 overexpression

In vitro studies were conducted using the PLK1 inhibitor volasertib and the PARP inhibitor olaparib, either alone or in combination, in PTC cell lines. Moreover, our findings indicate that inhibition of PLK1 can reinstate sensitivity in PARP inhibitor (PARPi) resistant TNBC cell lines. Our results shed light on the role of PLK1 in the pathogenesis and prognosis of Middle Eastern BC and support the potential clinical development of combined inhibition of PLK1 and PARP, a strategy that could potentially broaden the use of PLK1 and PARP inhibitors beyond BC cases lacking BRCA.

Bioinformatics analysis suggested that rs27770 A>G affects PLK1 mRNA secondary structure and alters the hsa-miR-100-5p/PLK1 interaction by forming an additional seedless binding site. This racial variation caused PLK1 to be more vulnerable to hsa-miR-100-5p inhibition, resulting in hsa-miR-100-5p being more favorable for HCC prognosis in the Asian population.

The expression levels and active phosphorylation levels of PLK1 were significantly increased in NK/T cell lymphoma, and patients with overexpression of PLK1 and p-PLK1 had a poorer prognosis.

The efficacy of Rigosertib (RGS), targeting RAS/PI3K, CDKs and PLKs, and Poloxin (Pol), specifically targeting the PLK1 polo-box domain, was tested in TP53-mutated NCI-H295R, MUC-1, and CU-ACC2 cells and in TP53-wild-type CU-ACC1...TP53-mutated ACC cell lines demonstrated better response to PLK1i than wild-type CU-ACC1. These data suggest PLK1i may be a promising targeted treatment of a subset of ACC patients, pre-selected according to tumour genetic signature.

We further show that high PLK1-expressing human breast tumors display gene expression patterns associated with SASP, NF-κβ signaling, and immune suppression. These findings underscore the need to understand the immune landscape in CIN tumors to identify more effective therapies, potentially combining immune checkpoint or NF-κβ inhibitors with current treatments.

Moreover, epidermal growth factor receptor (EGFR) activation induced the upregulation of acetyl-tubulin in docetaxel-resistant PCa cells. These findings demonstrated that the EGFR-mediated upregulated expression of acetyl-tubulin played an important role in docetaxel-resistant PCa.

Fingolimod can promote the arrest in G0/G1 of SCC9 cells, and PLK1 is a key targeted gene for the treatment of HNSC. Fingolimod can inhibit cell proliferation caused by PLK1 over-expression.

In conclusion, pharmacologic PLK1 inhibition by BI6727 and GSK461364A blocked survival of CCA cells by several mechanisms. Our study provides evidence that BI6727 and GSK461364A could be alternative drugs and have potential implications at the clinical level for CCA therapy.

The prognostic role of PLK1 in BC is molecular subtype-dependent. As PLK1 inhibitors are introduced to clinical trials for several cancer types, our study supports evaluation of the pharmacological inhibition of PLK1 as an attractive therapeutic target in TNBC. However, in luminal BC, PLK1 prognostic role remains controversial.

HDAC7 can be phosphorylated at SER155, once phosphorylated it can translocate from the cytoplasm to the nucleus...We have employed an original approach, a compound screening, to identify potential modulators of HDAC7. Our data suggest that PLK1 and AURORA B can play a pivotal role in modulate HDAC7 activity and localization, further experiments are needed to better characterized this exciting hypothesis

Tectoridin synergized with PLK1 inhibitor to suppress autophagy and ferroptosis but promoted caspase-3-mediated apoptosis in A549 cells. Our findings highlight a potential drug target and the combination therapy strategy of PLK1 inhibitor and tectoridin for LUAD patients.

To suppress the activation of PLK1, the PLK1 inhibitor BI2536 was administered...Furthermore, the in vivo model proved that cell mitochondrial function and chorionic villi development are both hampered by PLK1 suppression. Our findings revealed that the PLK1/TRAF2/NF-κB axis plays a crucial role in RPL-induced chorionic villi dysfunction by regulating mitochondrial dynamics and apoptosis and might be a potential therapeutic target in the clinic.

Our findings provide clinical and pre-clinical evidence to characterize the role of PLK1 in promoting PCa and novel insights into the regulatory mechanism of PLK1 in the TME. We also provide strong support for the clinical potential of targeting STAT6 for advanced PCa therapy.

The results of the molecular dynamic MD simulation diagram were obtained to reinforce the previous molecular docking results, which showed that both inhibitors remained stable in the active sites of the PLK1 protein (PDB code: 2RKU) for 50 ns. Finally, a check of the ADME-Tox properties of the two most active molecules showed that molecular N° 28 could represent a good drug candidate for the therapy of prostate cancer diseases.

In our study, we did not find RNA-seq PLK1 expression as a potential prognostic marker for prostate cancer. There was no survival difference between low PLK1 vs. high PLK1 expression.

Our analysis indicates that high PLK-1 expression is associated with aggressiveness and poor prognosis in malignant neoplasms. Therefore, PLK-1 may be a clinically valuable target for cancer treatment.

This study brings a new insight into the development of superior nonviral gene vectors for practical cancer treatment. Based on the results, the resulting nanoparticle-based gene drug formation is considered to have a highly successful chance in further translational nanomedicine applications.

Moreover, we revealed that MYCN directly regulated SMARCE1 transcription through binding to a non-canonical E-box of SMARCE1 promoter, thus enhancing SMARCE1-MYCN cooperativity. These findings establish SMARCE1 is a critical oncogenic factor in neuroblastoma and provide a new potential target for treatment of neuroblastoma with 17q21-ter gain and MYCN amplification.

The study showed that the substitution of electron-donating groups at the various position of the aromatic ring, which is bonded at the second position of the substituted 1,3,4-oxadiazole nucleus resulted in compounds with good binding energy and G score compared to the standard drugs, and hence, they can be further developed as potent PLK1 enzyme inhibitors.

A comparative bioinformatics analysis of 15 bone marrow and 10 peripheral blood samples from Hispanic B-ALL patients collected by the TARGET program, corroborated the genes observed, except for PIK3CG. We conclude the Mexican and the Hispanic B-ALL patients studied present common driver alterations and histotype-specific mutations that could facilitate risk stratification and diagnostic accuracy and serve as potential therapeutic targets.

We conclude that Plk1 regulates mutant IDH1 enzyme activity and mutant IDH2 ubiquitination in mitosis. Based on our results, we suggest that Plk1 can be a therapeutic target in mutant IDH-linked tumours.

Our study suggests that circPLK1 upregulation plays an important role in NSCLC progression by targeting miR-1294/HMGA1 axis. These data provide a theoretical basis for the development of therapeutic strategy targeting exosomal circPLK1 in NSCLC treatment.

PLK1, although a negative prognostic factor, but is a promising therapeutic target for treating TNBC patients.

Their expressions in LUAD were associated with tumor stages and relative abundance of tumor infiltrating immune cells, such as B cells, CD4+ T cells, and macrophages. Moreover, cell cycle, DNA replication, homologous recombination, mismatch repair, P53 signaling pathway, and small cell lung cancer signaling were significantly enriched in CDK1 and PLK1 high expression phenotype.CDK1 and PLK1 may be used as potential biomarkers and therapeutic targets for LUAD.

The H-score is a meaningful measure of PLK1 expression in lung tumour tissue. Using the optimal cut point of 5.99 we identified a group of patients with early-stage NSCLC at high risk of relapse. This translated across to OS whereby those with a score of 9.29 and above were at increased risk of death.

However, the inhibition of FUNDC1 abolished the positive effect of PLK1 on H9c2 cells mentioned above. In conclusion, PLK1 alleviated the ischemia reperfusion induced myocardial damage by inducing the mitophagy in a p-AMPK/FUNDC1 signaling dependent pathway.

Global methylation survival analysis showed that prognostic value of PLK1/2/4 methylation remained the same significant trend between two lung cancer subtypes, whereas prognostic value of PLK3 methylation lacked consistency. Taken together, these results provided instructive insights into a comprehensive evaluation for advanced therapeutic strategy based on epigenetic evidences.

High Plk1 expression conferred a resistant phenotype of ccRCC to targeted therapeutics such as sunitinib, in vitro, in vivo, and in metastatic ccRCC patients. Importantly, high Plk1 expression was defined in a subpopulation of ccRCC patients that are refractory to current therapies. Hence, we propose a therapeutic paradigm for improving outcomes of ccRCC patients.

Here, we provided sufficient evidence of PLK1 overexpression in cervical cancer. The overexpression of PLK1 in cervical cancer and the contributory effect of it on clinical progression indicated the hopeful prospect of PLK1 as a biomarker for cervical cancer.

On the other hand, we discuss recent evidence that unveils synthetic lethality induction by PLK1 inhibition in BRCA1-deficient cancers cells. This previously unforeseen therapeutic link between PLK1 and BRCA1 is promising because it defines novel therapeutic opportunities for PLK1i not only for breast cancer (i.e. TNBCs with BRCA1 deficiencies), but also for other types of cancers with BRCA1-deficiencies, such as pancreatic and prostate cancers.