FOXM1 overexpression is associated with cisplatin resistance in non-small cell lung cancer and mediates sensitivity to cisplatin in A549 cells via the JNK/mitochondrial pathway

Liu, Y; Chen, X; Gu, Yuchen; Zhu, Ling; Qian, Yamin; Pei, Dong‐Sheng; Zhang, W; Shu, Yin

doi:10.4149/neo_2015_008

Cited by 24 publications

(8 citation statements)

References 44 publications

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“…Reports indicate that numerous signaling pathways, such as the Wnt (23), p38 MAPK (40), PI3K/ Akt (41) and TGFβ/Smad2/STAT3/STAT5 pathways (42), are involved in the complex mechanism of DDP resistance. It is also worth mentioning that cell autophagy by hypoxia induced or exacerbated by FOXM1 (43) via the JNK/mitochondrial pathway (44), may decrease the susceptibility of lung cancer cells to cisplatin-induced apoptosis (45). Large numbers of surveys indicate the complexity of the mechanism underlying the regulation of cisplatin resistance.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of miR-203 increases the sensitivity of NSCLC A549/H460 cell lines to cisplatin by targeting Dickkopf-1

Cheng

Zhang

et al. 2017

Oncology Reports

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The number of new lung cancer cases diagnosed yearly is high, and the mortality rate has not substantially declined. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and adenocarcinoma accounts for the largest proportion of NSCLC. Currently, platinum-based combined chemotherapy, particularly cisplatin (DDP) is still the main form of treatment for advanced NSCLC. However, cisplatin resistance often occurs in patients who receive chemotherapy. Previous studies offer various explanations for how miRNAs affect cisplatin resistance, but the underlying mechanism remains largely unknown. The present study was designed to focus on miR-203 and Dickkopf-1 (DKK1), investigating the potential mechanisms involved in cisplatin resistance in tissues of lung adenocarcinoma and A549/H460 cell lines. In DDP-sensitive NSCLC samples, miR-203 was expressed at a higher level when compared with this level in DDP-insensitive samples, while DKK1 mRNA was expressed at a relatively low level as indicated by qRT-PCR. Dual luciferase reporter assay revealed that DKK1 is a target gene of miR-203 in A549 and H460 cells. Upregulation of miR-203 reduced the IC50 value of cisplatin in the A549 and H460 cells by inhibiting cell growth and promoting cell apoptosis. Similar effects of tumor inhibition and cisplatin sensitization were verified in vivo. Further research showed that both overexpression of miR-203 and knockdown of DKK1 increased the sensitization to DDP with a lower IC50 value. Upon DKK1 knockdown, overexpression of miR-203 had no added effects on the sensitivity of the cells. In addition, miR-203 was unable to sensitize cells with DKK1 that lacked the 3' untranslated region (3'UTR). We conclude that miR-203 targets the 3'UTR of DKK1, and increases cisplatin sensitivity in A549/H460 cell lines.

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Section: Discussionmentioning

confidence: 99%

Overexpression of miR-203 increases the sensitivity of NSCLC A549/H460 cell lines to cisplatin by targeting Dickkopf-1

Cheng

Zhang

et al. 2017

Oncology Reports

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“…However, the role of the MAPK pathway in regulating apoptosis of cancer cells, particularly in drug-resistant cancer cells is complex. A previous study showed p38 MAPK activation was associated with apoptosis induction in A549/DDP cells [20], and another report indicated that JNK activation may contribute to apoptosis in A549/DDP cells [21]. Therefore, further studies are required to elucidate the link between MAPK signaling and apoptosis during HVJ-E induced cytotoxicity.…”

Section: Discussionmentioning

confidence: 96%

Inactivated Sendai virus induces apoptosis and autophagy via the PI3K/Akt/mTOR/p70S6K pathway in human non-small cell lung cancer cells

Zhang

Zhu

et al. 2015

Biochemical and Biophysical Research Communications

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“…Through TEAD interaction YAP controls a set of genes such as CTGF, cyr61, survivin, amphiregulin and AXL [11,14,46], and some of them have been associated with drug resistance [47]. [12], and it has been related to the drug resistance in a variety of cancers [48][49][50].…”

Section: Discussionmentioning

confidence: 99%

Crosstalk between Nrf2 and YAP contributes to maintaining the antioxidant potential and chemoresistance in bladder cancer

Ciamporcero

Daga

Pizzimenti

et al. 2018

Free Radical Biology and Medicine

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Redox adaptation plays an important role in cancer cells drug resistance. The antioxidant response is principally mediated by the transcription factor Nrf2, that induces the transcriptional activation of several genes involved in GSH synthesis, chemoresistance, and cytoprotection. YAP is emerging as a key mediator of chemoresistance in a variety of cancers, but its role in controlling the antioxidant status of the cells is yet elusive. Here, we show that impairing YAP protein expression reduced GSH content and Nrf2 protein and mRNA expression in bladder cancer cells. Moreover, in YAP knocked down cells the expression of FOXM1, a transcription factor involved in Nrf2 transcription, was down-regulated and the silencing of FOXM1 reduced Nrf2 expression. On the other hand, the silencing of Nrf2, as well as the depletion of GSH by BSO treatment, inhibited YAP expression, suggesting that cross-talk exists between YAP and Nrf2 proteins. Importantly, we found that silencing either YAP or Nrf2 enhanced sensitivity of bladder cancer cells to cytotoxic agents and reduced their migration. Furthermore, the inhibition of both YAP and Nrf2 expressions significantly increased cytotoxic drug sensitivity and synergistically reduced the migration of chemoresistant bladder cancer cells. These findings provide a rationale for targeting these transcriptional regulators in patients with chemoresistant bladder cancer, expressing high YAP and bearing a proficient antioxidant system.

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FOXM1 overexpression is associated with cisplatin resistance in non-small cell lung cancer and mediates sensitivity to cisplatin in A549 cells via the JNK/mitochondrial pathway

Cited by 24 publications

References 44 publications

Overexpression of miR-203 increases the sensitivity of NSCLC A549/H460 cell lines to cisplatin by targeting Dickkopf-1

Overexpression of miR-203 increases the sensitivity of NSCLC A549/H460 cell lines to cisplatin by targeting Dickkopf-1

Inactivated Sendai virus induces apoptosis and autophagy via the PI3K/Akt/mTOR/p70S6K pathway in human non-small cell lung cancer cells

Crosstalk between Nrf2 and YAP contributes to maintaining the antioxidant potential and chemoresistance in bladder cancer

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