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http://ir.nhri.org.tw/handle/3990099045/12280
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| Title: | STAT3 represses miR-145-5p to exacerbate HER3 expression for surviving EGFR-TKIs in lung cancers |
| Authors: | Cheng, CC;Chiang, YW;Lim, KH;Chang, JS;Ho, AS;Chang, YF |
| Contributors: | Institute of Molecular and Genomic Medicine |
| Abstract: | HER3 exerts resistance against epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), resulting in tumor relapse in lung cancers. Previously, we have demonstrated that EGFR induces HER3 overexpression and that contributes to the formation of cancer stem-like tumorspheres. However, the cellular mechanism of EGFR in regulating HER3 expression was obscure. We hypothesized that EGFR-downstream STAT3 participates in HER3 expression since STAT3 contributes to cancer stemness and surviving EGFR-TKIs. First, RNAseq was used to uncover the potential genes involving in formation of lung cancer HCC827-derived stem-like tumorspheres. EGFR-positive lung cancer cell lines (HCC827, A549, H1975) were individually treated with a panel containing 172 compounds which targeting to stem cell-associated genes in order to searching potential agents against EGFR-positive lung cancers. In addition, gene knockdown and RNAseq were used for investigating the molecular mechanism of STAT3 on regulating tumor progression and survival of lung cancers. We found that BBI608, a STAT3 inhibitor, was a potential therapeutic agent specifically reducing the cell viability of EGFR-positive lung cancers. Interestingly, the inhibitory effects caused by BBI608 were similar with that derived from YM155, an ILF3 inhibitor, both compounds reduced G9a-mediated HER3 expression. We, furthermore, demonstrated that STAT3 upregulated G9a to silence miR-145-5p for exacerbating HER3 expression in this study. In conclusion, this study figured out the potential cellular function of STAT3 in EGFR-positive lung cancers. We also evaluated that BBI608 was potential to eradicate EGFR-positive lung cancers and demonstrated that STAT3 regulated expression of HER3, indicating that STAT3 was a reliable therapeutic target against EGFR-TKI-resistant lung cancers. |
| Date: | 2019-07 |
| Relation: | Cancer Research. 2019 Jul;79(13, Suppl.):Abstract number 3028. |
| Link to: | http://dx.doi.org/10.1158/1538-7445.Sabcs18-3028 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000488279401472 |
| Appears in Collections: | [其他] 會議論文/會議摘要
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