Integrated pan‐cancer of <i>AURKA</i> expression and drug sensitivity analysis reveals increased expression of <i>AURKA</i> is responsible for drug resistance

Miralaei, Noushin; Majd, Ahmad; Ghaedi, Kamran; Peymani, Maryam; Safaei, Masoomeh

doi:10.1002/cam4.4161

Cited by 21 publications

(21 citation statements)

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“…String interaction results indicated interplay of signaling molecules of AURKA pathway in SiHa/RR. AURKA was found to be strongly interacted with p53, Gadd45a, Akt and PCNA and NFκB [23][24][25]. Hyper-proliferative potential of SiHa/RR aided in increased migration and invasion capabilities as found from the result of wound healing assay where SiHa/RR lled the gap at a much faster rate compared to SiHa.…”

Section: Discussionmentioning

confidence: 86%

AURKA/NFκB Axis: A Key Determinant of Radioresistance in Cervical Squamous Carcinoma Cells

Das¹,

Ray²,

Mahapatra³

et al. 2022

Arch Clin Biomed Res

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Background: Cervical cancer being one of the leading gynaecological cancers, possess a major threat by its ever-increasing trend of global recurrence events. Radioresistance is one of the major challenges confronted during the treatment of cervical cancer. Radioresistance in cancer cells is manifested by increased rate of cellular proliferation, migration-invasion and cell cycle alterations. Aurora Kinase A (AURKA), a mitotic serine/threonine kinase was found to be overexpressed in cancers and is associated with development of acquired therapy resistance. The principal objective of this study revolved with exploring the mechanisms by which AURKA confers radioadaptive response in cervical cancer cells.Methods and Results: Parental cervical squamous carcinoma cell line SiHa was subjected to recurrent insult by fractionated dose of X-irradiation. Finally, a resistant subline (SiHa/RR) was isolated at 40Gy. SiHa/RR exhibited higher expression of AURKA/ pAURKA along with the signaling molecules that are favored by this kinase (HIF1α, pAkt, NFκB) vis-à-vis lower expressions of the molecules that are generally suppressed by AURKA (p53, Gadd45a). Surprisingly, inhibition of AURKA in SiHa/RR showed improved radiosensitivity by reducing the wound healing capacity, sphere forming ability and enhancing radiation induced apoptosis. Ectopic overexpression of AURKA gave rise to radioresistant phenotype in parental SiHa by stimulating nuclear translocation of NFκB. This pattern of increased nuclear localization of NFκB was also observed in resistant subline as a consequence of activation and overexpression of AURKA.Conclusion: These ndings strengthened the involvement of AURKA in radioresistance via activating NFκB mediated signaling pathway to deliver radioresistant associated adaptive complexities.

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Section: Discussionmentioning

confidence: 86%

AURKA/NFκB Axis: A Key Determinant of Radioresistance in Cervical Squamous Carcinoma Cells

Das¹,

Ray²,

Mahapatra³

et al. 2022

Arch Clin Biomed Res

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“…Sperm-associated antigen 5 ( SPAG5 , also known as asstrin) is involved in mitotic spindle formation and chromosome segregation, and has carcinogenic effects in tumorigenesis of various cancer types ( Huang & Li, 2020 ). AURKA is a serine/threonine kinase that is critical for the control of mitotic progression, centrosomal maturation/separation, and mitotic spindle function ( Miralaei et al, 2021 ). Studies have found that AURKA mRNA expression is an independent predictor of poor prognosis in patients with NSCLC ( Al-Khafaji et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes and biological pathways in Chinese lung cancer population using bioinformatics analysis

Liu

Liao

et al. 2022

PeerJ

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Background Identification of accurate prognostic biomarkers is still particularly urgent for improving the poor survival of lung cancer patients. In this study, we aimed to identity the potential biomarkers in Chinese lung cancer population via bioinformatics analysis. Methods In this study, the differentially expressed genes (DEGs) in lung cancer were identified using six datasets from Gene Expression Omnibus (GEO) database. Subsequently, enrichment analysis was conducted to evaluate the underlying molecular mechanisms involved in progression of lung cancer. Protein-protein interaction (PPI) and CytoHubba analysis were performed to determine the hub genes. The GEPIA, Human Protein Atlas (HPA), Kaplan-Meier plotter, and TIMER databases were used to explore the hub genes. The receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic value of hub genes. Reverse transcription quantitative PCR (qRT-PCR) was used to validate the expression levels of hub genes in 10 pairs of lung cancer paired tissues. Results A total of 499 overlapping DEGs (160 upregulated and 339 downregulated genes) were identified in the microarray datasets. DEGs were mainly associated with pathways in cancer, focal adhesion, and protein digestion and absorption. There were nine hub genes (CDKN3, MKI67, CEP55, SPAG5, AURKA, TOP2A, UBE2C, CHEK1 and BIRC5) identified by PPI and module analysis. In GEPIA database, the expression levels of these genes in lung cancer tissues were significantly upregulated compared with normal lung tissues. The results of prognostic analysis showed that relatively higher expression of hub genes was associated with poor prognosis of lung cancer. In HPA database, most hub genes were highly expressed in lung cancer tissues. The hub genes have good diagnostic efficiency in lung cancer and normal tissues. The expression of any hub gene was associated with the infiltration of at least two immune cells. qRT-PCR confirmed that the expression level of CDKN3, MKI67, CEP55, SPAG5, AURKA, TOP2A were highly expressed in lung cancer tissues. Conclusions The hub genes and functional pathways identified in this study may contribute to understand the molecular mechanisms of lung cancer. Our findings may provide new therapeutic targets for lung cancer patients.

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“… Confirmed to have Burkholderia pseudomallei infection according to colony cultures 6 using body fluid specimens (blood, pleural fluid, sputum, pus, urine, secretions, etc. ); Administered with antibiotics and necessary treatment by Haikou Hospital of Xiangya School of Medicine, Central South University following the susceptibility test; …”

Section: Methodsmentioning

confidence: 99%

“…Confirmed to have Burkholderia pseudomallei infection according to colony cultures 6 using body fluid specimens (blood, pleural fluid, sputum, pus, urine, secretions, etc. );…”

Section: Methodsmentioning

confidence: 99%

A clinical study on clinical features,manifestations and drug resistance of melioidosis

Huang¹,

Yan²,

Han³

et al. 2022

Pak J Med Sci

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Objectives: To explore the clinical features, manifestations and drug resistance of melioidosis. Methods: The clinical data of 45 melioidosis patients treated by Affiliated Haikou Hospital of Xiangya Medical College, Central South University during January 2015 and January 2020 were studied. Informaiton collected included age, birthplace, area of residence, sex, ethnic group, clinical symptoms or signs, colony culture results, degree of drug resistance, treatment regimens and outcomes, department of initial diagnosis, and specimen type, thereby giving an analysis of the clinical features, manifestations, and treatment outcomes of the disease. Body fluids were obtained from all patients to analyze the drug resistance of the bacterium Burkholderia pseudomallei based on colony culture and susceptibility test results. Results: In the 45 cases of melioidosis, the clinical manifestations predominantly included low fever (31.11%), pulmonary infection (22.22%); auxiliary examinations often suggested increases in C reactive protein (CRP) (73.33%), white blood cell count (#WBC) (68.89%) and procalcitonin (PCT) (66.67%); susceptibility test results showed that Burkholderia pseudomallei yielded high sensitive rate to antibacterials including trimethoprim–sulfamethoxazole (SXT) (88.89%),ceftazidime (CAZ)(93.33%), meropenem (MEM) (100.00%), imipenem (IPM)(100.00%); Of the 45 melioidosis patients, 23 were cured (51.11%), and 21 showed an improvement (33.33%) or remained stable (13.33%); A relatively high percentage of the patients experienced post-discharge recurrence/aggravation (recurrence within six months: 4.44%; recurrence within a year: 6.67%). Conclusions: Low fever, pulmonary infection, and increases in serum inflammatory markers are major clinical features of melioidosis. Burkholderia pseudomallei presents high resistance rates to antibacterials such as GEN, FEP, AMP, and IPM. doi: https://doi.org/10.12669/pjms.38.8.5506 How to cite this:Hui H, Sheng Y, Han X, Wang S, Zhang G, Wei X. A clinical study on clinical features, manifestations and drug resistance of melioidosis. Pak J Med Sci. 2022;38(8):---------. doi: https://doi.org/10.12669/pjms.38.8.5506 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Integrated pan‐cancer of AURKA expression and drug sensitivity analysis reveals increased expression of AURKA is responsible for drug resistance

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 21 publications

References 77 publications

AURKA/NFκB Axis: A Key Determinant of Radioresistance in Cervical Squamous Carcinoma Cells

AURKA/NFκB Axis: A Key Determinant of Radioresistance in Cervical Squamous Carcinoma Cells

Identification of key genes and biological pathways in Chinese lung cancer population using bioinformatics analysis

A clinical study on clinical features,manifestations and drug resistance of melioidosis

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