Knockdown of <i>KLF5</i> promotes cisplatin‐induced cell apoptosis via regulating DNA damage checkpoint proteins in non‐small cell lung cancer

Zhang, Hao; Shao, Fei; Guo, Wei; Gao, Yibo

doi:10.1111/1759-7714.13046

Cited by 14 publications

(18 citation statements)

References 27 publications

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“…A previous study has revealed, in a small number of PTC tumor samples, an association between KLF5 and lymphnode metastasis, but not other clinical parameters, which could be due to the small number of patient samples in their cohort [ 10 ]. The prognostic significance of KLF5 upregulation seen in our cohort is similar to previously reported studies in other organ sites, like pancreatic [ 6 ], gastric [ 18 ] and lung cancers [ 19 ]. However, KLF5 upregulation is not an independent prognostic factor in multivariant analysis.…”

Section: Discussionsupporting

confidence: 91%

Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer

Pratheeshkumar

Siraj

Divya

et al. 2021

Cancers

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The Krüppel-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in several solid tumors, but its role in PTC remains unclear. We investigated the expression of KLF5 protein in a large cohort of PTC patient samples and explored its functional role and mechanism in PTC cell lines in vitro and in vivo. KLF5 overexpression was observed in 65.1% of all PTC cases and it was significantly associated with aggressive clinico-pathological parameters and poor outcome. Given the significant association between KLF5 and HIF-1α overexpression in PTC patients, we investigated the functional correlation between KLF5 and HIF-1α in PTC cells. Indeed, the analysis revealed the co-immunoprecipitation of KLF5 with HIF-1α in PTC cells. We also identified KLF5-binding sites in the HIF-1α promoter that specifically bound to KLF5 protein. Mechanistically, KLF5 promoted PTC cell growth, invasion, migration, and angiogenesis, while KLF5 downregulation via specific inhibitor or siRNA reverses its action in vitro. Importantly, the silencing of KLF5 decreases the self-renewal ability of spheroids generated from PTC cells. In addition, the depletion of KLF5 reduces PTC xenograft growth in vivo. These findings suggest KLF5 can be a possible new molecular therapeutic target for a subset of PTC.

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Section: Discussionsupporting

confidence: 91%

Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer

Pratheeshkumar

Siraj

Divya

et al. 2021

Cancers

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“…In vitro, chemotherapy combined with Chk1 inhibitor can significantly reduce the survival rate of NSCLC stem cell [54]. Targeting Chk2 reduced phosphorylation and increased the efficacy of cisplatin [55]. Researches showed that genomic changes of IRS1 could lead to development of lung cancer [56].…”

Section: Discussionmentioning

confidence: 99%

Construction and Validation of a Protein Prognostic Model for Lung Squamous Cell Carcinoma

Fang¹,

Liu²,

Weng³

et al. 2020

Int. J. Med. Sci.

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Lung squamous cell carcinoma (LUSCC), as the major type of lung cancer, has high morbidity and mortality rates. The prognostic markers for LUSCC are much fewer than lung adenocarcinoma. Besides, protein biomarkers have advantages of economy, accuracy and stability. The aim of this study was to construct a protein prognostic model for LUSCC. The protein expression data of LUSCC were downloaded from The Cancer Protein Atlas (TCPA) database. Clinical data of LUSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 237 proteins were identified from 325 cases of LUSCC patients based on the TCPA and TCGA database. According to Kaplan-Meier survival analysis, univariate and multivariate Cox analysis, a prognostic prediction model was established which was consisted of 6 proteins (CHK1_pS345, CHK2, IRS1, PAXILLIN, BRCA2 and BRAF_pS445). After calculating the risk values of each patient according to the coefficient of each protein in the risk model, the LUSCC patients were divided into high risk group and low risk group. The survival analysis demonstrated that there was significant difference between these two groups (p= 4.877e−05). The area under the curve (AUC) value of the receiver operating characteristic (ROC) curve was 0.699, which suggesting that the prognostic risk model could effectively predict the survival of LUSCC patients. Univariate and multivariate analysis indicated that this prognostic model could be used as independent prognosis factors for LUSCC patients. Proteins co-expression analysis showed that there were 21 proteins co-expressed with the proteins in the risk model. In conclusion, our study constructed a protein prognostic model, which could effectively predict the prognosis of LUSCC patients.

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“…Compared with the LRSI group, KLF5 was the most significant gene for CNV in the HRSI group. KLF5 plays an important role in the DNA damage response by regulating DNA damage checkpoint proteins and is associated with cisplatin DDP resistance [ 33 – 35 ]. The relationship between KLF5 and radiotherapy sensitivity needs to be discovered.…”

Section: Discussionmentioning

confidence: 99%

Multiomics Differences in Lung Squamous Cell Carcinoma Patients with High Radiosensitivity Index Compared with Those with Low Radiosensitivity Index

Yuan

Zhuang

et al. 2021

Disease Markers

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Objectives. Radiosensitivity Index (RSI) can predict intrinsic radiotherapy sensitivity. We analyzed multiomics characteristics in lung squamous cell carcinoma between high and low RSI groups, which may help understand the underlying molecular mechanism of radiosensitivity and guide optional treatment for patients in the future. Methods. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data were used to download clinical data, mRNA, microRNA, and lncRNA expression. Differential analyses, including mRNA, miRNA, lncRNA, and G.O. and KEGG, and GSVA analyses, were performed with R. Gene set enrichment analysis was done by GSEA. miRNA-differentially expressed gene network and ceRNA network were analyzed and graphed by the Cytoscape software. Results. In TCGA data, 542 patients were obtained, including 171 in the low RSI group (LRSI) and 371 in the high RSI group (HRSI). In RNAseq, 558 significantly differentially expressed genes (DEGs) were obtained. KRT6A was the most significantly upregulated gene and IDO1 was the most significantly downregulated gene. In miRNAseq, miR-1269a was the most significantly upregulated. In lncRNAseq, LINC01871 was the most upregulated. A 66-pair interaction between differentially expressed genes and miRNAs and an 11-pair interaction between differential lncRNAs and miRNAs consisted of a ceRNA network, of which miR-184 and miR-490-3p were located in the center. In the GEO data, there were 40 DEGs. A total of 17 genes were founded in both databases, such as ADAM23, AHNAK2, BST2, COL11A1, CXCL13, FBN2, IFI27, IFI44L, MAGEA6, and PTGR1. GSVA analysis revealed 31 significant pathways. GSEA found 87 gene sets enriched in HRSI and 91 gene sets in LRSI. G.O. and KEGG of RNA expression levels revealed that these genes were most enriched in T cell activation and cytokine−cytokine receptor interaction. Conclusions. Patients with lung squamous cell carcinoma have different multiomics characteristics between two groups. These differences may have an essential significance with radiotherapy effect.

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Knockdown of KLF5 promotes cisplatin‐induced cell apoptosis via regulating DNA damage checkpoint proteins in non‐small cell lung cancer

Cited by 14 publications

References 27 publications

Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer

Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer

Construction and Validation of a Protein Prognostic Model for Lung Squamous Cell Carcinoma

Multiomics Differences in Lung Squamous Cell Carcinoma Patients with High Radiosensitivity Index Compared with Those with Low Radiosensitivity Index

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