PLK1 as a potential prognostic marker of gastric cancer through MEK-ERK pathway on PDTX models

Dang, Sheng-Chun; Fan, Yi-Yi; Cui, Lei; Chen, Jixiang; Qu, Junle; Gu, Min

doi:10.2147/ott.s169880

Cited by 17 publications

(15 citation statements)

References 39 publications

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“…PLK1 was reported to promote the abnormalities of early cervical columnar epithelial cells ( Oh et al, 2014 ; Yang et al, 2017 ). The overexpression of PLK1 was found in various types of cancers and was associated with poor prognosis of cancer patients ( Weng Ng et al, 2016 ; Lin et al, 2017 ; Li et al, 2017 ; Dang et al, 2018 ). Although several researches involved PLK1 in cervical cancer ( Yang et al, 2017 ; Li et al, 2011 ; Zhang et al, 2009 ; Gao et al, 2006 ; Zuco et al, 2015 ; Chhavi et al, 2010 ), PLK1 expression in cervical cancer was detected with single methods and small samples by those studies.…”

Section: Introductionmentioning

confidence: 99%

Polo like kinase 1 expression in cervical cancer tissues generated from multiple detection methods

Pang

Guo

et al. 2020

PeerJ

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Background Existing studies of PLK1 in cervical cancer had several flaws. The methods adopted by those studies of detecting PLK1 expression in cervical cancer were single and there lacks comprehensive evaluation of the clinico-pathological significance of PLK1 in cervical cancer. Methods A total of 303 cervical tissue samples were collected for in-house tissue microarrays. Immunohistochemistry was performed for evaluating PLK1 expression between cervical cancer (including cervical squamous cell carcinoma (CESC) and cervical adenocarcinoma) and non-cancer samples. The Expression Atlas database was searched for querying PLK1 expression in different cervical cancer cell lines and different tissues in the context of pan-cancer. Standard mean difference (SMD) was calculated and the summarized receiver’s operating characteristics (SROC) curves were plotted for integrated tissue microarrays, exterior high-throughput microarrays and RNA sequencing data as further verification. The effect of PLK1 expression on the overall survival, disease-free survival and event-free survival of cervical cancer patients was analyzed through Kaplan Meier survival curves for cervical cancer patients from RNA-seq and GSE44001 datasets. The gene mutation and alteration status of PLK1 in cervical cancer was inspected in COSMIC and cBioPortal databases. Functional enrichment analysis was performed for genes correlated with PLK1 from aggregated RNA-seq and microarrays. Results A total of 963 cervical cancer samples and 178 non-cancer samples were collected from in-house tissue microarrays and exterior microarrays and RNA-seq datasets. The combined expression analysis supported overexpression of PLK1 in CESC, cervical adenocarcinoma and all types of cervical cancer (SMD = 1.59, 95%CI [0.56–2.63]; SMD = 2.99, 95%CI [0.75–5.24]; SMD = 1.57, 95% CI [0.85–2.29]) and the significant power of PLK1 expression in distinguishing CESC or all types of cervical cancer samples from non-cancer samples (AUC = 0.94, AUC = 0.92). Kaplan-Meier survival curves showed that the event-free survival rate of cervical cancer patients with higher expression of PLK1 was shorter than that of patients with lower PLK1 (HR = 2.020, P = 0.0197). Genetic alteration of PLK1 including missense mutation and mRNA low occurred in 6% of cervical cancer samples profiled in mRNA expression. Genes positively or negatively correlated with PLK1 were mainly assembled in pathways such as DNA replication, cell cycle, mismatch repair, Ras signaling pathway, melanoma, EGFR tyrosine kinase inhibitor resistance and homologous recombination (P < 0.05). Conclusions 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.

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Section: Introductionmentioning

confidence: 99%

Polo like kinase 1 expression in cervical cancer tissues generated from multiple detection methods

Pang

Guo

et al. 2020

PeerJ

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“…PLK1 overexpression is regarded as a marker for poor prognosis in a number of types of cancer, and PLK1 has become an attractive target for anticancer therapy over the past several years ( 19 ). Studies have demonstrated that PLK1 is overexpressed in a variety of cancers, and that it regulates proliferation, migration and apoptosis on various cancer types, such as gastric cancer ( 35 ), non-small cell lung cancer ( 36 ) and pancreatic cancer ( 37 ). Moreover, it has been suggested that PLK1 silencing may lead to cell cycle arrest and apoptosis in AML ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA ZEB2‑AS1 affects cell proliferation and apoptosis via the�miR‑122‑5p/PLK1�axis in acute myeloid leukemia

Guan

Liu

Wang³

et al. 2020

Int J Mol Med

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Acute myeloid leukemia (AML) is a highly heterogeneous disease featured by the clonal accumulation of immature myeloid cells. Zinc finger E-box binding homeobox 2 (ZEB2)-antisense RNA 1 (AS1) has been verified to participate in the progression of several types of cancer, including AML. However, the potential mechanisms of ZEB2-AS1 in AML have not yet been fully elucidated. The present study aimed to elucidate the role and regulatory mechanisms of ZEB2-AS1 in AML. The expression of ZEB2-AS1, microRNA-122-5p (miRNA/miR-122-5p) and polo-like kinase 1 (PLK1) was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in AML tissues or cells. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) assay and apoptosis assay, respectively. The protein levels were examined by western blot analysis. The targeted sequence between miR-122-5p and ZEB2-AS1 or PLK1 was predicted using an online database and verified by dual-luciferase reporter assay. A mouse tumor xenograft model was established to confirm the effects of ZEB2-AS1 on tumor growth in vivo. The results revealed that the expression levels of ZEB2-AS1 and PLK1 were upregulated, while those of miR-122-5p were downregulated in AML tissues and cells. The knockdown of ZEB2-AS1 inhibited proliferation and induced apoptosis in vitro , and inhibited tumor growth in vivo . By experimental verification, ZEB2-AS1 was found to negatively regulate miR-122-5p expression and PLK1 was found to be a target gene of miR-122-5p. Furthermore, ZEB2-AS1 was verified to regulate the expression of PLK1 by sponging miR-122-5p in AML cells. On the whole, the findings of the present study demonstrate that ZEB2-AS1 promotes cell proliferation and inhibits apoptosis, at least partly by targeting PLK1 mediated by miR-122-5p in AML cells.

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“…6,7 Preceding studies have illustrated that overexpressed PLK1 is correlated with poor survival rate in numerous types of cancers as breast, melanoma, and non-small cell lung cancer. 8 Indeed, PLK1 inhibition makes cells unable to complete mitosis, finally resulting in cell death, 9,10 suggesting that PLK1 may be a powerful therapeutic target for cancer control. [11][12][13] Volasertib (Vola) is a selective and powerful cell cycle kinase inhibitor that prompts mitotic arrest and apoptosis by targeting PLK1.…”

Section: Introductionmentioning

confidence: 99%

Polo-like kinase 1 as a promising diagnostic biomarker and potential therapeutic target for hepatocellular carcinoma

et al. 2020

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Hepatocellular carcinoma is a major cause of cancer mortality worldwide. The outcome of hepatocellular carcinoma depends mainly on its early diagnosis. To date, the performance of traditional biomarkers is unsatisfactory. Polo-like kinase 1 is a serine/threonine kinase that plays essential roles in cell cycle progression and deoxyribonucleic acid damage. Moreover, polo-like kinase 1 knockdown decreases the survival of hepatocellular carcinoma cells; therefore, polo-like kinase 1 is an attractive target for anticancer treatments. Nobiletin, a natural polymethoxy flavonoid, exhibits a potential antiproliferative effect against a wide variety of cancers. This study targets to identify a reliable diagnostic biomarker for hepatocellular carcinoma and provide a potential therapeutic target for its treatment. Polo-like kinase 1 levels were analyzed in 44 hepatocellular carcinoma patients, 33 non-hepatocellular carcinoma liver cirrhosis patients and 15 healthy controls using the enzyme-linked immunosorbent assay method. Receiver operating characteristics curve analysis was used to establish a predictive model for polo-like kinase 1 relative to α-fetoprotein in hepatocellular carcinoma diagnosis. Furthermore, in the in vitro study, gene expressions were assessed by quantitative polymerase chain reaction in two human hepatocellular carcinoma cell lines after treatment with doxorubicin and polo-like kinase 1 inhibitor volasertib (Vola) either alone or in combination with nobiletin. Cell viability was also determined using the crystal violet assay.: Serum polo-like kinase 1 levels in hepatocellular carcinoma patients were significantly higher than liver cirrhosis and control groups (p < 0.0001). Polo-like kinase 1 showed a reasonable sensitivity, specificity, positive predictive value, and negative predictive value in hepatocellular carcinoma diagnosis. Moreover, nobiletin improved inhibition of cell growth induced by Vola and doxorubicin. Regarding reverse transcription polymerase chain reaction results, nobiletin suppressed expressions of polo-like kinase 1 and proliferating cell nuclear antigen and elevated expressions of P53, poly (ADPribose) polymerase 1, and caspase-3. Nobiletin/doxorubicin and nobiletin/Vola showed a significant increase in caspase-3 activity indicating cell apoptosis. Polo-like kinase 1 may be a potential biomarker for hepatocellular carcinoma diagnosis and follow-up during treatment with chemotherapies. In addition, nobiletin synergistically potentiates the doxorubicin and Vola-mediated anticancer effect that may be attributed partly to suppression of polo-like kinase 1 and proliferating cell nuclear antigen expression and enhancement of chemotherapy-induced apoptosis.

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PLK1 as a potential prognostic marker of gastric cancer through MEK-ERK pathway on PDTX models

Cited by 17 publications

References 39 publications

Polo like kinase 1 expression in cervical cancer tissues generated from multiple detection methods

Polo like kinase 1 expression in cervical cancer tissues generated from multiple detection methods

Long non‑coding RNA ZEB2‑AS1 affects cell proliferation and apoptosis via the�miR‑122‑5p/PLK1�axis in acute myeloid leukemia

Polo-like kinase 1 as a promising diagnostic biomarker and potential therapeutic target for hepatocellular carcinoma

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