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Long non-coding RNA BC087858 induces non-T790M mutation acquired resistance to EGFR-TKIs by activating PI3K/AKT and MEK/ERK pathways and EMT in non-small-cell lung cancer
| Content Provider | Semantic Scholar |
|---|---|
| Author | Pan, Hui Peng Jiang, Tao Cheng, Ningning Wang, Qi Ren, Shengxiang Li, Xuefei Zhao, Chao Zhang, Limin Cai, Weijing Zhou, Caicun |
| Copyright Year | 2016 |
| Abstract | Our previous study demonstrated that long non-coding RNA (lncRNA) BC087858 could stimulate acquired resistance to EGFR-TKIs in non-small cell lung (NSCLC) but the specific regulatory mechanism remained unknown. We aimed to explore the role and mechanism of lncRNA BC087858 on EGFR-TKIs acquired resistance. LncRNA BC087858 mRNA expression was detected by reverse transcription polymerase chain reaction in different NSCLC cell lines and tissues. The relationship between BC087858 expression and clinicopathological factors was performed by Cox multivariate regression analysis. Small-interfering RNA, flow cytometry and trans-well assay were conducted to explore the biological functions of BC087858. Western blotting was used to analyze the target proteins expression. Over-expression was observed in NSCLC cells and patients with acquired resistance to EGFR-TKIs and significantly associated with a shorter progression-free survival (PFS) (12.0 vs. 17.0 months, P = 0.0217) in tumors with respond to EGFR-TKIs. The significant relationship was not observed in patients with T790M mutation (median PFS 17.6 vs. 12.5 months, P = 0.522) but in patients with non-T790M (median PFS 8.0 vs. 18.25 months,P = 0.0427). Down-regulation of BC087858 could significantly promote PC9/R and PC9/G2 cells invasion (P < 0.05; respectively). BC087858 knockdown restored gefitinib sensitivity in acquired resistant cells with non-T790M and inhibited the activation of the PI3K/AKT and MEK/ERK pathways and epithelial-mesenchymal transition (EMT) via up- regulating ZEB1 and Snail. In conclusion, LncRNA BC087858 could promote cells invasion and induce non-T790M mutation acquired resistance to EGFR-TKIs by activating PI3K/AKT and MEK/ERK pathways and EMT via up- regulating ZEB1 and Snail in NSCLC. |
| Starting Page | 49948 |
| Ending Page | 49960 |
| Page Count | 13 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.oncotarget.com/index.php?journal=oncotarget&op=download&page=article&path%5B%5D=10521&path%5B%5D=33241 |
| PubMed reference number | 27409677v1 |
| Alternate Webpage(s) | https://doi.org/10.18632/oncotarget.10521 |
| DOI | 10.18632/oncotarget.10521 |
| Journal | Oncotarget |
| Volume Number | 7 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Body tissue Carcinoma of lung Flow Cytometry Mitogen-Activated Protein Kinase Kinases Mutation Neoplasms Non-Small Cell Lung Carcinoma Patients Progression-Free Survival Proto-Oncogene Proteins c-akt RNA, Long Untranslated Reverse Transcriptase Polymerase Chain Reaction Reverse Transcription Structure of parenchyma of lung Western Blotting ZEB1 gene epithelial to mesenchymal transition gefitinib long noncoding RNA Fas-AS1, human non-T, non-B childhood acute lymphoblastic leukemia non-T, non-B, cALLa positive childhood acute lymphoblastic leukemia |
| Content Type | Text |
| Resource Type | Article |
