FKBP3 Promotes Proliferation of Non-Small Cell Lung Cancer Cells through Regulating Sp1/HDAC2/p27

Zhu, Wenzhuo; Zhao, Li; Xiong, Liwen; Yu, Xiuchong; Chen, Xi; Lin, Qiang

doi:10.7150/thno.18067

Cited by 49 publications

(51 citation statements)

References 27 publications

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“…Cohort 2 contains 100 patients with TNBC who had gone through radiotherapy between 2016 and 2017. The paraffin‐embedded specimens from cohort 1 and 2 were available for immunohistochemical (IHC) staining using anti‐CPNE1 antibody (Abcam; ab66898; 1:100) as previously described 16 . Protein expression was quantified using a visual grading system based on the intensity of staining (graded on a scale of 0‐4: 0,<5%; 1, 5%‐25%; 2, 25%‐50%; 3, 50%‐75%; 4, >75%).…”

Section: Methodsmentioning

confidence: 99%

“…The paraffin-embedded specimens from cohort 1 and 2 were available for immunohistochemical (IHC) staining using anti-CPNE1 antibody (Abcam; ab66898; 1:100) as previously described. 16 Protein expression was quantified using a visual grading system based on the intensity of staining (graded on a scale of 0-4: 0,<5%; 1, 5%-25%; 2, 25%-50%; 3, 50%-75%; 4, >75%). Score more than equal to 2 was defined as CPNE1 high-expression group otherwise defined as CPNE1 low-expression group.…”

Section: Patients and Tissue Samplesmentioning

confidence: 99%

“…C, CPNE1 expression levels were measured in the tumor cells isolated from primary patients with TNBC (n = 16) from cohort 1. D, After primary isolated TNBC cells (n = 16) with different CPNE1 expression levels (high: case 2, 4, 5, 8, 10, 12, 13, 15 and low: case 1,3,6,7,9,11,14,16) were irradiated with 4 Gy X-ray, the cell viability was measured at 0 and 24 hours. ***P < .001 compared with low + IR group (TNBC cells with lower CPNE1 expression levels were irradiated with 4 Gy X-ray).IHC, immunohistochemical; IR, irradiation; TNBC, triple-negative breast cancer [Color figure can be viewed at wileyonlinelibrary.com] F I G U R E 6 CPNE1 inhibited the radiosensitivity in TNBC cells.…”

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confidence: 99%

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CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple‐negative breast cancer

Shao

Zhang³

et al. 2020

Molecular Carcinogenesis

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Elevated expression of Copine 1 (CPNE1) has been observed in multiple cancers; however, the underlying mechanisms by which it affects cancer cells are unclear. We aimed to study the effect of CPNE1 on the tumorigenesis and radioresistance of triple‐negative breast cancer (TNBC). Quantitative real‐time polymerase chain reaction was used to detect the expression of CPNE1 in TNBC tissues and cell lines. Western blot, immunohistochemistry, and immunofluorescence were used to investigate the levels of CPNE1, p‐AKT, AKT, cleaved caspase‐3, cleaved PARP1, and γ‐H2AX. Cell viability and apoptosis were measured by CCK‐8 and flow cytometry, respectively. CPNE1 was overexpressed in TNBC tissues and cell lines and was associated with tumor size, distant metastases, and survival rates of patients with TNBC. Moreover, function study shows that CPNE1 promoted cell viability and inhibited cell apoptosis in vitro and inhibited the radiosensitivity of TNBC. Importantly, inactivation of AKT signaling inhibited the tumorigenesis and radioresistance mediated by CPNE1 in TNBC cells. In vivo xenograft study also shows that CPNE1 knockdown inhibited tumor growth and promoted cell apoptosis. Overall, our findings suggest that CPNE1 promotes tumorigenesis and radioresistance in TNBC by regulating AKT activation and targeted CPNE1 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

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Section: Methodsmentioning

confidence: 99%

Section: Patients and Tissue Samplesmentioning

confidence: 99%

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confidence: 99%

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CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple‐negative breast cancer

Shao

Zhang³

et al. 2020

Molecular Carcinogenesis

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“…FKBPs have long been regarded as important regulators of the response to immunosuppressants FK506 and as molecular chaperones binding to different cellular receptors or targets [19]. More lately, various evidence has suggested that this complicated protein family might also play their roles in carcinogenesis, progression and chemoresistance of cancers [20][21][22].…”

Section: Discussionmentioning

confidence: 99%

FKBP-related ncRNA-mRNA axis in breast cancer

Xiong

Chen²,

Zheng

et al. 2020

Preprint

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KEYWORDSbreast cancer; microRNA; long noncoding RNA; FK506-binding protein; bioinformatic analysis.3 Abstract Background Breast cancer (BC) is a disease with morbidity ranking the first of women worldwidely.FK506-binding protein (FKBP) family has been demonstrated to possess various functions by interacting with different molecular targets in BC. However, a comprehensive ncRNA-mRNA regulatory axis of FKBP has not yet been reported. Methods FKBP related miRNAs were obtained from miRWalk database. Then, potential lncRNAs, transcription factors as well as mRNAs of screened differentially expressed miRNAs (DE-miRNAs) were analysed by using LncBase v.2, miRGen v3 and miRWalk database. Additionally, differential expression and prognostic analysis of lncRNAs were evaluated using TANRIC database. Next, GO annotation and KEGG pathway analysis were processed using DAVID database. Protein-Protein Interaction (PPI) network was established and hub genes were identified using STRING database. Finally, differential expression and prognostic analysis of hub genes were further conducted using UALCAN and bc-GenExMiner v4.2 database, respectively. Results Eleven DE-miRNAs, consisting of four FKBP4 related DE-miRNAs and seven FKBP5 related DE-miRNAs, were screened. 482 predicted lncRNAs were found for DE-miRNAs. Then, expression and prognostic results of nine of top twenty lncRNAs of BC were significantly identified. LINC00662 and LINC00963 expression were significantly associated with patients' overall survival (OS). Then, nine potential upstream transcription factors were identified in motifs of DE-miRNAs. 320 target genes were identified for GO annotation and KEGG pathway analysis, which were mainly enriched in cysteine-type endopeptidase activity involved in apoptotic process. Construction and analysis in PPI network showed that RAB7A was selected as a hub gene with the toppest connectivity scores. Differential expression analysis of nine in top ten hub genes of BC were significantly identified. RAB7A and ARRB1 expression were significantly related with BC patients' OS. Conclusions In current study, we firstly established a predicted FKBP-related ncRNA-mRNA regulatory network, thus exploring a comprehensive interpretation of molecular mechanisms and providing potential clues in seeking novel therapeutics for BC. In the future, much more experiments should be conducted to verify our findings. Background Breast cancer (BC) is the most widespread and deadly non-cutaneous tumor in worldwide women[1]. 4 Early detection and comprehensive treatments, which consist of surgery, radiation, chemotherapy, endocrine therapy and targeted therapy, have significantly improved the prognosis in BC patients. However, BC is a heterogeneous disease of various different genetical, pathological, and clinical subtypes[2]. Even though intensive efforts have been made in both basic researches and clinical studies, it's still necessary to find more reliable markers to further improve therapeutics for BC patients.FK506-binding protein (FKBP) family in Homo...

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“…Following the observation that the combination of Pem and 125 I was more effective in the NSCLC cell models compared with the single treatment groups, the underlying mechanisms involved in the anti-tumor effects were subsequently investigated. Based on the striking ADAM17 phenotype, the protein and mRNA expression levels of key proteins associated with apoptosis and proliferation, such as Bcl-2, Bax, p21 and p27 (20,21), in H460 cells treated with the aforementioned reagents were detected using western blot analysis and RT-qPCR. As presented in Fig.…”

Section: Adam17 Is Downregulated By the Combination Treatmentmentioning

confidence: 99%

Combination of pembrolizumab and 125I attenuates the aggressiveness of non‑small cell lung cancer

et al. 2020

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Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated mortality. Therapies targeting programmed cell death 1 ligand 1 (PD1L1) have promising effects on NSCLC. However, resistance to targeted therapy has become the main problem and the underling molecular mechanism remains unclear. In the present study, the expression of PD1L1 in NSCLC was determined and the association with clinicopathological characteristics was analyzed. A combination therapy was also constructed, including pembrolizumab (Pem) and iodine-125 ( 125 I), which represented an efficient strategy for the treatment of NSCLC. The expression of PD1L1 was upregulated in NSCLC tissues and positively correlated with the Ki-67 index, pathological subtypes and risk stages. A higher level of PD1L1 expression was associated with poorer survival in patients with NSCLC, which could be used as a prognostic indicator. When NSCLC cells were cultured in the presence of Pem and 125 I seeds, the combination treatment significantly abrogated the tumor proliferation and aggressiveness through the inhibition of matrix metalloproteinase-2 and -9 secretion. Flow cytometry analysis revealed pembrolizumab combined with 125 I contributed to a higher rate of apoptosis and cell cycle arrest, indicating that the combination treatment improved the resistance to immunotherapy. Furthermore, the associated molecular mechanism was the dysregulation of ADAM metallopeptidase domain 17. The findings from the present study revealed that PD1L1 could be used as a predictive biomarker, and the application of combination treatment of pembrolizumab and 125 I showed promising effects on NSCLC.Abbreviations: PD1L1, programmed cell death 1 ligand 1; ADAM17, ADAM metallopeptidase domain 17; RT-qPCR, reverse transcriptase-quantitative polymerase chain reaction; PI, propidium iodide; MMP, matrix metalloproteinase; FCM, flow cytometry Key words: non-small cell lung cancer, programmed cell death 1 ligand 1, iodine-125, targeted therapy

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FKBP3 Promotes Proliferation of Non-Small Cell Lung Cancer Cells through Regulating Sp1/HDAC2/p27

Cited by 49 publications

References 27 publications

CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple‐negative breast cancer

CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple‐negative breast cancer

FKBP-related ncRNA-mRNA axis in breast cancer

Combination of pembrolizumab and 125I attenuates the aggressiveness of non‑small cell lung cancer

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