Knockdown of Snail, a novel zinc finger transcription factor, via RNA interference increases A549 cell sensitivity to cisplatin via JNK/mitochondrial pathway

Wu, Zhuo; Wang, Yan; Zhuo, Xianlu; Zhang, Yunsong; Xu-jun, AO; Chen, Zhengtang

doi:10.1016/j.lungcan.2008.02.007

Cited by 87 publications

(58 citation statements)

References 36 publications

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“…Liu et al [29] observed that SET (SET nuclear proto-oncogene)-mediated NDRG1 inhibition is involved in acquisition of an EMT phenotype and cisplatin resistance in human lung cancer. Suppression of Snail, a key gene inducing EMT, could significantly reverse A549 NSCLC cell resistance to DDP [30]. The above-mentioned studies suggest a correlation between EMT and DDP resistance.…”

Section: Zeb2 Directly Suppresses Mir-203 Expression By Binding To Itmentioning

confidence: 88%

Direct interaction between miR-203 and ZEB2 suppresses epithelial–mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance

Duan¹,

Fu²,

Gao³

et al. 2016

ABBS

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miR-203 is a tumor suppressor which participates in the pathogenesis of many tumors including lung adenocarcinoma. However, the role of miR-203 in suppressing chemotherapy resistance to cisplatin (cis-diamminedichloroplatinum; DDP) as well as its molecular mechanism is still to be determined in lung adenocarcinoma. In this study, we found that miR-203 decreased lung cancer cell migration and invasion, and that increased miR-203 expression sensitized lung adenocarcinoma cells to DDP in vitro. Furthermore, ZEB2 was found to be a direct target of miR-203, which induces epithelial-mesenchymal transition (EMT) signal. Knock-down of ZEB2 significantly increased DDP chemosensitivity in lung adenocarcinoma. More interestingly, we also demonstrated that ZEB2 could directly bind to E-box of the miR-203 promoter and suppress its expression in lung adenocarcinoma. Our data reveal that miR-203 serves as a negative feedback by directly suppressing the upstream ZEB2 gene, which inhibits EMT signaling and reduces chemoresistance of DDP. Together, these results highlight a feedback loop between miR-203 and ZEB2, which participates in the pathogenesis of lung adenocarcinoma.

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Section: Zeb2 Directly Suppresses Mir-203 Expression By Binding To Itmentioning

confidence: 88%

Direct interaction between miR-203 and ZEB2 suppresses epithelial–mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance

Duan¹,

Fu²,

Gao³

et al. 2016

ABBS

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show abstract

“…Snail has been reported to regulate components of the early to late G 1 transition and the G 1 -S checkpoint and to promote cell survival after genotoxic stress in breast, lung, and pancreatic adenocarcinomas via regulation of several gene products and pathways (47)(48)(49)(50)(51)(52). In all cases, depletion of endogenous Snail by RNA interference led to increased sensitivity to DNA damage accompanied by increased expression of the proapoptotic factors identified as targets of Snail.…”

Section: Discussionmentioning

confidence: 99%

Pivotal Roles of Snail Inhibition and RKIP Induction by the Proteasome Inhibitor NPI-0052 in Tumor Cell Chemoimmunosensitization

et al. 2009

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The novel proteasome inhibitor NPI-0052 has been shown to sensitize tumor cells to apoptosis by various chemotherapeutic drugs and tumor necrosis factor-related apoptosisinducing ligand (TRAIL), although the mechanisms involved are not clear. We hypothesized that NPI-0052-mediated sensitization may result from NF-κB inhibition and downstream modulation of the metastasis inducer Snail and the metastasis suppressor/immunosurveillance cancer gene product Raf-1 kinase inhibitory protein (RKIP). Human prostate cancer cell lines were used as models, as they express different levels of these proteins. We show that NPI-0052 inhibits both NF-κB and Snail and induces RKIP expression, thus resulting in cell sensitization to CDDP and TRAIL. The direct role of NF-κB inhibition in sensitization was corroborated with the NF-κB inhibitor DHMEQ, which mimicked NPI-0052 in sensitization and inhibition of Snail and induction of RKIP. The direct role of Snail inhibition by NPI-0052 in sensitization was shown with Snail small interfering RNA, which reversed resistance and induced RKIP. Likewise, the direct role of RKIP induction in sensitization was revealed by both overexpression of RKIP (mimicking NPI-0052) and RKIP small interfering RNA that inhibited NPI-0052-mediated sensitization. These findings show that NPI-0052 modifies the NF-κB-Snail-RKIP circuitry in tumor cells and results in downstream inhibition of antiapoptotic gene products and chemoimmunosensitization. The findings also identified Snail and RKIP as targets for reversal of resistance. [Cancer Res 2009;69(21):8376-85]

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“…32 Frequent multidrug resistance to chemotherapeutic agents is a main barrier to possibly curative treatments for advanced NSCLC. 33 It is therefore required new therapeutic agents that selectively target altered signaling pathways.…”

Section: Downregulation Of Pc4 Inhibits Tumorigenicity Of A549 Cells mentioning

confidence: 99%

Human positive coactivator 4 is a potential novel therapeutic target in non-small cell lung cancer

et al. 2012

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Transcriptional positive coactivator 4 (PC4) is a multifunctional nuclear protein that has important roles in DNA transcription, replication, repair and heterochromatinization. However, the role of PC4 in cancer remains to be clarified. Several studies propose that PC4 may act as a putative tumor suppressor. Here, we demonstrate for the first time that PC4 may represent a potential therapeutic target in non-small cell lung cancer (NSCLC). PC4 protein expression is significantly upregulated in NSCLC carcinoma tissues compared with their adjacent noncancerous counterparts as shown by immunohistochemical staining and western blotting in 104 pairs of formalin-fixed human NSCLC specimens and 6 fresh NSCLC samples. Knockdown of PC4 expression by sequence-specific small interfering RNA (siRNA) in human NSCLC cells (A549, H460 and H358) significantly inhibits the growth of cancer cells by the induction of cell cycle arrest and the increase of cell apoptosis in vitro. Interrupting the PC4 signaling pathway by injection of the PC4 siRNA liposome complex produced an effective regression of pre-established A549 cell xenografts in mice through growth inhibition and increased apoptosis. These results indicated that PC4 could be an attractive new therapeutic target for the treatment of NSCLC.

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Knockdown of Snail, a novel zinc finger transcription factor, via RNA interference increases A549 cell sensitivity to cisplatin via JNK/mitochondrial pathway

Cited by 87 publications

References 36 publications

Direct interaction between miR-203 and ZEB2 suppresses epithelial–mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance

Direct interaction between miR-203 and ZEB2 suppresses epithelial–mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance

Pivotal Roles of Snail Inhibition and RKIP Induction by the Proteasome Inhibitor NPI-0052 in Tumor Cell Chemoimmunosensitization

Human positive coactivator 4 is a potential novel therapeutic target in non-small cell lung cancer

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Knockdown of Snail, a novel zinc finger transcription factor, via RNA interference increases A549 cell sensitivity to cisplatin via JNK/mitochondrial pathway

Cited by 87 publications

References 36 publications

Direct interaction between miR-203 and ZEB2 suppresses epithelial&ndash;mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance

Direct interaction between miR-203 and ZEB2 suppresses epithelial&ndash;mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance

Pivotal Roles of Snail Inhibition and RKIP Induction by the Proteasome Inhibitor NPI-0052 in Tumor Cell Chemoimmunosensitization

Human positive coactivator 4 is a potential novel therapeutic target in non-small cell lung cancer

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Direct interaction between miR-203 and ZEB2 suppresses epithelial–mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance

Direct interaction between miR-203 and ZEB2 suppresses epithelial–mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance