Sepantronium Bromide (YM155) induces disruption of the ILF3/p54nrb complex, which is required for survivin expression

Yamauchi, Tomohiro; Nakamura, Naoto; Hiramoto, Masashi; Yuri, Masatoshi; Yokota, Hiroyuki; Naitou, Masanori; Takeuchi, Masahiro; Yamanaka, Kazuhiro; Kita, Aya; Nakahara, Takahito; Kinoyama, Isao; Matsuhisa, Akira; Kaneko, Naoki; Koutoku, Hiroshi; Sasamata, Masao; Kobori, Masato; Katou, Masao; Tawara, Shuichi; Kawabata, Sueo; Furuichi, Kiyoshi

doi:10.1016/j.bbrc.2012.07.103

Cited by 61 publications

(51 citation statements)

References 31 publications

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“…It also induces dissociation of the ILF3-p54nrb complex which positively regulates survivin expression [20]. However, there is mounting evidence that YM155-induced effects are not solely due to the inhibition of survivin [21].…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative, DNA intercalation and redox cycling activities of dioxonaphtho[2,3-d]imidazolium analogs of YM155: A structure–activity relationship study

Sim

Yee

et al. 2015

European Journal of Medicinal Chemistry

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Section: Introductionmentioning

confidence: 99%

Antiproliferative, DNA intercalation and redox cycling activities of dioxonaphtho[2,3-d]imidazolium analogs of YM155: A structure–activity relationship study

Sim

Yee

et al. 2015

European Journal of Medicinal Chemistry

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“…It competes the binding sites of Sp1 on survivin promoter [16] and thereby disrupts the ILF3 transcriptional complex [17; 18]. Clinical trials of YM155 used as a single agent or in combination with other drugs, have been carried out in various solid tumors, including non-small cell lung cancer [19; 20], prostate cancer [21] and melanoma [22].…”

Section: Introductionmentioning

confidence: 99%

Influence of survivin-targeted therapy on chemosensitivity in the treatment of acute myeloid leukemia

Huang¹,

Lyu

Wang

2015

Cancer Letters

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Overexpression of survivin is observed in various hematological malignancies, including acute myeloid leukemia (AML). Studies show that elevated expression of survivin correlates with a worse clinic outcome in AML patients. It remains unclear whether inhibition of survivin may alter the efficacy of chemotherapy against AML. Here, we evaluate the effects of specific knockdown of survivin on AML cells’ sensitivity to chemotherapy, and investigate the therapeutic potential of the transcription inhibitor of survivin YM155 either alone or in combination with chemotherapeutic agents. We found Kasumi-1 and HL-60 cells had relatively higher expression levels of survivin among all AML cell lines tested. Specific knockdown of survivin in Kasumi-1 and HL-60 cells resulted in: inhibition of cell proliferation; cell cycle G2/M arrest; induction of DNA damage response and apoptosis. Downregulation of survivin enhanced etoposide- or doxorubicin-induced anti-proliferative/anti-survival activity in AML cells. The small molecule inhibitor YM155 reduced survivin in a dose- and time-dependent manner and trigged apoptosis in Kasumi-1 and HL-60 cells. The combinatorial effects of YM155 and chemotherapeutics were either synergetic or antagonistic, depending upon the drugs used for combination and the type of AML cells being treated. Collectively, our data demonstrate that survivin plays an important role in the maintenance and proliferation of AML cells. While specific knockdown of survivin enhances chemosensitivity, the combinations of YM155 and chemotherapeutic agents exhibit synergetic or antagonistic effects on AML cells. Our findings provide a rationale for further assessment of survivin-targeted therapy in the treatment of patients with AML.

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“…NONO regulates the transcription of rhodopsin [28] and survivin [29], and functions as a coactivator of transcription factors androgen receptor [30], estrogen receptor alpha [31], progesterone receptor [32], thyroid hormone receptor [33], retinoid X receptor [33], and SPI1 [34] to regulate the expression of their respective target genes. Previous studies show that NONO is elevated in many human cancers, including prostate cancer [35], melanoma [36], and neuroblastoma [37].…”

Section: Discussionmentioning

confidence: 99%

Ets-1 promoter-associated noncoding RNA regulates the NONO/ERG/Ets-1 axis to drive gastric cancer progression

Chen

Hong

et al. 2018

Oncogene

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Emerging studies have indicated the essential functions of long noncoding RNAs (lncRNAs) during cancer progression. However, whether lncRNAs contribute to the upregulation of v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1), an established oncogenic protein facilitating tumor invasion and metastasis, in gastric cancer remains elusive. Herein, we identified Ets-1 promoter-associated noncoding RNA (pancEts-1) as a novel lncRNA associated with the gastric cancer progression via mining of publicly available datasets and rapid amplification of cDNA ends. RNA pull-down, RNA immunoprecipitation, in vitro binding, and RNA electrophoretic mobility shift assays indicated the binding of pancEts-1 to non-POU domain containing octamer binding (NONO) protein. Mechanistically, pancEts-1 facilitated the physical interaction between NONO and Ets related gene (ERG), resulting in increased ERG transactivation and transcription of Ets-1 associated with gastric cancer progression. In addition, pancEts-1 facilitated the growth and aggressiveness of gastric cancer cells via interacting with NONO. In gastric cancer tissues, pancEts-1, NONO, and ERG were upregulated and significantly correlated with Ets-1 levels. High levels of pancEts-1, NONO, ERG, or Ets-1 were respectively associated with poor survival of gastric cancer patients, whereas simultaneous expression of all of them (HR = 3.012, P = 0.105) was not an independent prognostic factor for predicting clinical outcome. Overall, these results demonstrate that lncRNA pancEts-1 exhibits oncogenic properties that drive the progression of gastric cancer via regulating the NONO/ERG/Ets-1 axis.

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Sepantronium Bromide (YM155) induces disruption of the ILF3/p54nrb complex, which is required for survivin expression

Cited by 61 publications

References 31 publications

Antiproliferative, DNA intercalation and redox cycling activities of dioxonaphtho[2,3-d]imidazolium analogs of YM155: A structure–activity relationship study

Antiproliferative, DNA intercalation and redox cycling activities of dioxonaphtho[2,3-d]imidazolium analogs of YM155: A structure–activity relationship study

Influence of survivin-targeted therapy on chemosensitivity in the treatment of acute myeloid leukemia

Ets-1 promoter-associated noncoding RNA regulates the NONO/ERG/Ets-1 axis to drive gastric cancer progression

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