LncRNAs GIHCG and SPINT1-AS1 Are Crucial Factors for Pan-Cancer Cells Sensitivity to Lapatinib.

摘要: Lapatinib is a small molecule inhibitor of EGFR (HER1) and ERBB2 (HER2) receptors, which used for treatment advanced or metastatic breast cancer. To find the drug resistance mechanisms EGFR/ERBB2 positive tumors, we analyzed possible effects lncRNAs. In this study, using CCLE (Cancer Cell Line Encyclopedia) database, explored relationship between lncRNAs sensitivity/resistance, then validated those findings through in vitro experiments. We found that expression activation ERBB pathway was significantly related to sensitivity. GO (Gene Oncology) analysis top 10 pathways showed sensitivity positively correlated with cell keratin, epithelial differentiation, cell-cell junction, while negatively signatures extracellular matrix. Forty-four differentially expressed were sensitive resistant groups (fold-change > 1.5, P < 0.01). Gene set variation (GSVA) performed based on 44 genes pathways. Five identified as hub molecules. Co-expression network constructed by more than five 199 pathways, three (GIHCG, SPINT1-AS1, MAGI2-AS3) 47 close-related The epithelium-derived cancers groups, but no significance non-epithelium-derived cancer cells. Correlation SPINT1-AS1 (R = -0.715, 0.001) GIHCG 0.557, 0.013) IC50 further experiments, knockdown enhanced susceptibility Lapatinib, high level biomarker NCI-N87 MCF7 cells Lapatinib. conclusions, involved regulating Up-regulation drug-resistant biomarker, up-regulation indicator.