FLNA is a Predictor of Chemoresistance and Poor Survival in Cervical Cancer

Jin, Yan-Ze; Pei, Chang-Zhu; Lu, Wen

doi:10.2217/bmm-2016-0056

Cited by 21 publications

(16 citation statements)

References 29 publications

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“…FLNA, coding for filamin A, a non-muscle actin filament cross-linking protein, is a downstream target of the nuclear transcription factor Sp1 [52], which is also regulated by ERK1/2 [53]. Reduced FLNA levels were observed in PEA-15AA-transfected cells in this study, and also correlated with increased cisplatin sensitivity in a mouse xenograft model [54] and with improved overall survival in patients [55] according to previous reports. Filamin a was also found to promote cancer growth [56] and to play an important role in repair of DNA damage [57].…”

Section: Discussionsupporting

confidence: 86%

Non-Phosphorylatable PEA-15 Sensitises SKOV-3 Ovarian Cancer Cells to Cisplatin

Dilruba

Grondana

Schiedel

et al. 2020

Cells

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The efficacy of cisplatin-based chemotherapy in ovarian cancer is often limited by the development of drug resistance. In most ovarian cancer cells, cisplatin activates extracellular signal-regulated kinase1/2 (ERK1/2) signalling. Phosphoprotein enriched in astrocytes (PEA-15) is a ubiquitously expressed protein, capable of sequestering ERK1/2 in the cytoplasm and inhibiting cell proliferation. This and other functions of PEA-15 are regulated by its phosphorylation status. In this study, the relevance of PEA-15 phosphorylation state for cisplatin sensitivity of ovarian carcinoma cells was examined. The results of MTT-assays indicated that overexpression of PEA-15AA (a non-phosphorylatable variant) sensitised SKOV-3 cells to cisplatin. Phosphomimetic PEA-15DD did not affect cell sensitivity to the drug. While PEA-15DD facilitates nuclear translocation of activated ERK1/2, PEA-15AA acts to sequester the kinase in the cytoplasm as shown by Western blot. Microarray data indicated deregulation of thirteen genes in PEA-15AA-transfected cells compared to non-transfected or PEA-15DD-transfected variants. Data derived from The Cancer Genome Atlas (TCGA) showed that the expression of seven of these genes including EGR1 (early growth response protein 1) and FLNA (filamin A) significantly correlated with the therapy outcome in cisplatin-treated cancer patients. Further analysis indicated the relevance of nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signalling for the favourable effect of PEA-15AA on cisplatin sensitivity. The results warrant further evaluation of the PEA-15 phosphorylation status as a potential candidate biomarker of response to cisplatin-based chemotherapy.

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Section: Discussionsupporting

confidence: 86%

Non-Phosphorylatable PEA-15 Sensitises SKOV-3 Ovarian Cancer Cells to Cisplatin

Dilruba

Grondana

Schiedel

et al. 2020

Cells

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“…Hence, high-risk predictors must be identified to enable stratified management. Filamin A (FLNa) can be used as a predictor of chemotherapy sensitivity and as a biomarker of prognosis ( 11 ), and uncoupling protein 2 (UCP2) can be used as an indicator of chemotherapy sensitivity in patients with advanced CC ( 12 ). The present study focused on FLNa and UCP2 and investigated their expression levels in CC, their roles in the development and progression of CC, and their value for early diagnosis and prognosis prediction of CC.…”

Section: Introductionmentioning

confidence: 99%

Role and mechanism of FLNa and UCP2 in the development of cervical cancer

et al. 2020

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Recent studies have reported that filamin A (FLNa) and uncoupling protein 2 (UCP2) are highly expressed in various types of cancer, but little is currently known about their roles in cervical cancer (CC). In the present study, immunohistochemical staining of paraffin sections of cervical tissues was performed in order to compare the differential expression of FLNa, UCP2, p16 and Ki67 between CC and high-grade intraepithelial neoplasia (HSIL). UCP2 and FLNa were knocked down in CC cell lines to investigate the effects on cell proliferation, cell cycle arrest, apoptosis, migration and invasion. In addition, the present study investigated the expression of cell-associated proteins [extracellular signal-regulated kinase (ERK), phosphorylated (p) ERK, protein kinase B (AKT), p-AKT and B-cell lymphoma-2 (Bcl-2)] and the mRNA levels of cellular proteins such as Ras, matrix metalloproteinase (MMP)-2 and MMP-9. FLNa and UCP2 expression levels were significantly higher in CC tissues than in HSIL tissues, with no significant differential expression of p16 or Ki67. UCP2 expression was significantly different in patients with clinical stage II or higher or lymph node metastasis compared with in other patients with cervical cancer. FLNa or UCP2 knockdown slowed or decreased SiHa and HeLa cell proliferation, migration and invasion, with no significant change in apoptosis, and downregulated the protein levels of p-ERK1/2, and the mRNA levels of Ras, MMP-2 and MMP-9. UCP2 knockdown arrested the cell cycle at the G 2 phase in SiHa and HeLa cells, while FLNa knockdown arrested the cell cycle at the G 2 phase in HeLa cells. The results of the present study revealed that FLNa and UCP2 play roles in the development and progression of CC via the Ras/MAPK/ERK signalling pathway. FLNa and UCP2 are superior to p16 and Ki67 for early prediction of CC, indicating that FLNa and UCP2 may be used for the early diagnosis of CC. UCP2 may be used to predict the prognosis of CC.

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“…Down regulation of the gene has been observed in a wide range of human malignant tumors, including gastric and renal cancer. However, some studies have reported that FLNA was significantly up-regulated in cervical cancer and has a good predictive effect, which can be used as a prognostic signature of cervical cancer (22). VCL encodes focal adhesion protein, participates in the formation of cytoskeleton and focal adhesion, and the gene also connects cells with extracellular matrix.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Key Genes for Pathogenesis and Prognosis in Prostate Cancer by Integrated Analysis of Gene Expression Profiles and the Cancer Genome Atlas

et al. 2020

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Background: Prostate cancer (PCa)is a malignancy of the urinary system with a high incidence, which is the second most common male cancer in the world. There are still huge challenges in the treatment of prostate cancer. It is urgent to screen out potential key biomarkers for the pathogenesis and prognosis of PCa. Methods: Multiple gene differential expression profile datasets of PCa tissues and normal prostate tissues were integrated analysis by R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the overlapping Differentially Expressed Genes (DEG) were performed. The STRING online database was used in conjunction with Cytospace software for protein-protein interaction (PPI) network analysis to define hub genes. The relative mRNA expression of hub genes was detected in Gene Expression Profiling Interactive Analysis (GEPIA) database. A prognostic gene signature was identified by Univariate and multivariate Cox regression analysis. Results: Three hundred twelve up-regulated genes and 85 down-regulated genes were identified from three gene expression profiles (GSE69223, GSE3325, GSE55945) and The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset. Seven hub genes (FGF2, FLNA, FLNC, VCL, CAV1, ACTC1, and MYLK) further were detected, which related to the pathogenesis of PCa. Seven prognostic genes (BCO1, BAIAP2L2, C7, AP000844.2, ASB9, MKI67P1, and TMEM272) were screened to construct a prognostic gene signature, which shows good predictive power for survival by the ROC curve analysis. Conclusions: We identified a robust set of new potential key genes in PCa, which would provide reliable biomarkers for early diagnosis and prognosis and would promote molecular targeting therapy for PCa.

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FLNA is a Predictor of Chemoresistance and Poor Survival in Cervical Cancer

Cited by 21 publications

References 29 publications

Non-Phosphorylatable PEA-15 Sensitises SKOV-3 Ovarian Cancer Cells to Cisplatin

Non-Phosphorylatable PEA-15 Sensitises SKOV-3 Ovarian Cancer Cells to Cisplatin

Role and mechanism of FLNa and UCP2 in the development of cervical cancer

Identification of Potential Key Genes for Pathogenesis and Prognosis in Prostate Cancer by Integrated Analysis of Gene Expression Profiles and the Cancer Genome Atlas

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