Zinc finger protein ZBTB20 promotes cell proliferation in non-small cell lung cancer through repression of FoxO1

FEBS Letters ◽  
2014 ◽  
Vol 588 (24) ◽  
pp. 4536-4542 ◽  
Author(s):  
Jun-gang Zhao ◽  
Kai-ming Ren ◽  
Jun Tang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Zinc Finger ◽  
Cell Lung Cancer ◽  
Zinc Finger Protein ◽  
Small Cell ◽  
Small Cell Lung ◽  
Finger Protein

scholarly journals Molecular Analysis of ZNF71 KRAB in Non-Small-Cell Lung Cancer

2021 ◽  
Vol 22 (7) ◽  
pp. 3752
Author(s):  
Qing Ye ◽  
Rehab Mohamed ◽  
Duaa Dukhlallah ◽  
Marieta Gencheva ◽  
Gangqing Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Zinc Finger ◽  
Cell Lung Cancer ◽  
Zinc Finger Protein ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Our previous study found that zinc finger protein 71 (ZNF71) mRNA expression was associated with chemosensitivity and its protein expression was prognostic of non-small-cell lung cancer (NSCLC). The Krüppel associated box (KRAB) transcriptional repression domain is commonly present in human zinc finger proteins, which are linked to imprinting, silencing of repetitive elements, proliferation, apoptosis, and cancer. This study revealed that ZNF71 KRAB had a significantly higher expression than the ZNF71 KRAB-less isoform in NSCLC tumors (n = 197) and cell lines (n = 117). Patients with higher ZNF71 KRAB expression had a significantly worse survival outcome than patients with lower ZNF71 KRAB expression (log-rank p = 0.04; hazard ratio (HR): 1.686 [1.026, 2.771]), whereas ZNF71 overall and KRAB-less expression levels were not prognostic in the same patient cohort. ZNF71 KRAB expression was associated with epithelial-to-mesenchymal transition (EMT) in both patient tumors and cell lines. ZNF71 KRAB was overexpressed in NSCLC cell lines resistant to docetaxel and paclitaxel treatment compared to chemo-sensitive cell lines, consistent with its association with poor prognosis in patients. Therefore, ZNF71 KRAB isoform is a more effective prognostic factor than ZNF71 overall and KRAB-less expression for NSCLC. Functional analysis using CRISPR-Cas9 and RNA interference (RNAi) screening data indicated that a knockdown/knockout of ZNF71 did not significantly affect NSCLC cell proliferation in vitro.

scholarly journals Ring Finger Protein 180 Suppresses Cell Proliferation and Energy Metabolism of Non-Small Cell Lung Cancer Through Down-Regulating C-myc

2020 ◽  
Author(s):  
Yi Ding ◽  
Yi Lu ◽  
Xinjie Xie ◽  
Lei Cao ◽  
Shiying Zheng
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Energy Metabolism ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Ring Finger ◽  
Small Cell ◽  
Ring Finger Protein ◽  
Small Cell Lung ◽  
Finger Protein

Abstract BackgroundNon-small cell lung cancer (NSCLC) causes a great number of cancer-related mortality worldwide, but the biomarkers for prognosis of NSCLC are scarce because of their inconsistent efficiency. Proteins containing RING finger domain are the key mediator for ubiquitination, which controls cell cycle and regulates tumor progression. Ring Finger Protein 180 (RNF180) has been reported to suppress gastric cancer, whereas its function in NSCLC is still unclear. In this study, the association between RNF180 expression and NSCLC as well as the effect of RNF180 in cellular proliferation and metabolism of NSCLC were investigated. MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining were performed to analyse RNF180 levels. Moreover, RNA interference (RNAi) and lentiviral-mediated vector transfections were performed to silence and overexpress RNF180. Further, Cell Counting Kit-8 (CCK-8) was used to assess its biological function in cell proliferation. A xenograft model was used to examine RNF180 function in vivo. ResultsWe found that the expression of RNF180 was decreased in NSCLC tissues, and its expression was positively correlated with the survival rate of NSCLC patients. Furthermore, the overexpression of RNF180 in NSCLC cells suppressed their proliferation, glycolytic activities, and mitochondrial respiration in vitro, and it restricted the tumorigenicity in mice. In addition, RNF180 knockdown promoted NSCLC cell proliferation and energy metabolism, whereas these promotive effects were counteracted by C-myc inhibitor. The underlying anti-NSCLC mechanism of RNF180 involved in the down-regulation of C-myc through ubiquitin-dependent degradation, and subsequently reduced C-myc downstream: lactate dehydrogenase-A (LDHA) and hexokinase-2 (HK2). ConclusionsThese results firstly indicated the anti-tumor properties of RNF180 and its significant correlation with NSCLC, which endorses RNF180 with the potential as efficient prognostic biomarker for tumor recurrence in NSCLC.

scholarly journals Midazolam increases cisplatin-sensitivity in non-small cell lung cancer (NSCLC) via the miR-194-5p/HOOK3 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tingting Sun ◽  
Jing Chen ◽  
Xuechao Sun ◽  
Guonian Wang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
Cisplatin Resistance ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Cisplatin Sensitivity

Abstract Backgrounds As previously reported, midazolam anesthesia exerts tumor-suppressing effects in non-small cell lung cancer (NSCLC), but the regulating effects of this drug on cisplatin-resistance in NSCLC have not been studied. Thus, we designed this study to investigate this issue and preliminarily delineate the potential molecular mechanisms. Methods We performed MTT assay and trypan blue staining assay to measure cell proliferation and viability. Cell apoptosis was examined by FCM. qRT-PCR and immunoblotting were performed to determine the expression levels of genes. The targeting sites between genes were predicted by bioinformatics analysis and were validated by dual-luciferase reporter gene system assay. Mice tumor-bearing models were established and the tumorigenesis was evaluated by measuring tumor weight and volume. Immunohistochemistry (IHC) was used to examine the pro-proliferative Ki67 protein expressions in mice tumor tissues. Results The cisplatin-resistant NSCLC (CR-NSCLC) cells were treated with high-dose cisplatin (50 μg/ml) and low-dose midazolam (10 μg/ml), and the results showed that midazolam suppressed cell proliferation and viability, and promoted cell apoptosis in cisplatin-treated CR-NSCLC cells. In addition, midazolam enhanced cisplatin-sensitivity in CR-NSCLC cell via modulating the miR-194-5p/hook microtubule-tethering protein 3 (HOOK3) axis. Specifically, midazolam upregulated miR-194-5p, but downregulated HOOK3 in the CR-NSCLC cells, and further results validated that miR-194-5p bound to the 3’ untranslated region (3’UTR) of HOOK3 mRNA for its inhibition. Also, midazolam downregulated HOOK3 in CR-NSCLC cells by upregulating miR-194-5p. Functional experiments validated that both miR-194-5p downregulation and HOOK3 upregulation abrogated the promoting effects of midazolam on cisplatin-sensitivity in CR-NSCLC cells. Conclusions Taken together, this study found that midazolam anesthesia reduced cisplatin-resistance in CR-NSCLC cells by regulating the miR-194-5p/HOOK3 axis, implying that midazolam could be used as adjuvant drug for NSCLC treatment in clinical practices.

scholarly journals Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

2018 ◽  
Vol 45 (6) ◽  
pp. 2213-2224 ◽  
Author(s):  
Meng Zhao ◽  
Yahui Liu ◽  
Ran Liu ◽  
Jin Qi ◽  
Yongwang Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11’s role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial–mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial–mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.

scholarly journals Long Noncoding RNA FAL1 Promotes Cell Proliferation, Invasion and Epithelial-Mesenchymal Transition Through the PTEN/AKT Signaling Axis in Non-Small Cell Lung Cancer

2017 ◽  
Vol 43 (1) ◽  
pp. 339-352 ◽  
Author(s):  
Chunfeng Pan ◽  
Guoliang Yao ◽  
Bin Liu ◽  
Teng Ma ◽  
Yang Xia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Noncoding Rna ◽  
Biological Effects ◽  
Small Cell ◽  
Chromosome 1 ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Background/Aims: Recently, long non-coding RNAs (lncRNAs) have been found to have many biological effects in different cancer stages. Several studies have revealed that focally amplified lncRNA on chromosome 1 (FAL1) regulates cancer progression via p21. However, the expression and mechanism of FAL1 in non-small cell lung cancer (NSCLC) still remain unclear. Methods: We detected the FAL1 level in NSCLC tissues and in established cell lines using quantitative real-time PCR and evaluated the clinical significance. FAL1 was silenced or overexpressed using siRNA or lentivirus to study whether FAL1 affected cell proliferation, invasion and migration. Xenograft growth and pulmonary metastasis were observed using nude mouse models. The mechanisms were explored with western blotting and immunohistochemistry. Results: FAL1 was significantly overexpressed in NSCLC compared with adjacent normal tissues, and a high level of FAL1 correlated with poor histological grade, increased lymph node metastasis and advanced TNM stage. Loss- and gain-of-function experiments in vitro verified that knockdown of FAL1 inhibited cell proliferation, invasion, migration and EMT via the PTEN/AKT pathway. Furthermore, an in vivo assay confirmed that overexpression of FAL1 facilitated tumor growth and metastasis. Conclusion: FAL1 may promote tumorigenesis and progression of NSCLC through the PTEN/AKT axis, which could lead to lncRNA-related diagnostics and therapeutics in NSCLC.

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