Skip to main content
. Author manuscript; available in PMC: 2022 Oct 15.
Published in final edited form as: Cancer Res. 2022 Apr 15;82(8):1534–1547. doi: 10.1158/0008-5472.CAN-20-0821

Figure 7: Modulation of LINC01510 or MET is partially responsible for the erlotinib response.

Figure 7:

A) (i) Representative western blot of MET in KMT5C mutant cells that were either untransfected (UT) or reverse transfected with siRNA control (sicont), siRNA to MET (siMET), or siRNA to LINC01510 (siLINC01510) for 96 hours. β-ACTIN serves as a loading control. Densitometry values normalized to β-ACTIN, and relative to UT are indicated. ii) Quantification of protein levels from three biological replicates as done in A(i). B) Expression of (i) MET and (ii) LINC01510 in KMT5C mutant cells that were either UT or reverse transfected with sicont, siMET or siLINC01510 for 96 hours. Data are normalized to GAPDH and are graphed relative to data from UT cells. C) Erlotinib dose response of KMT5C mutant cells following transfection with the indicted siRNAs. Twenty-four hours post transfection, cells were exposed to varying concentrations of erlotinib or DMSO for 72 hours. Post-normalization, the GI50 concentration of erlotinib was calculated. D) Proliferation of KMT5C mutant cells following transfection with the indicted siRNAs. Twenty-four hours post transfection, cells were exposed to erlotinib for 72 hours. Normalized data is represented relative to UT. One-way ANOVA followed by Dunnett’s Multiple Comparison test was used to evaluate significance. E) (i) Representative western blot of MET in KMT5C WT cells that were untransfected (UT), or transfected with pcDNA3.1 control plasmid or plasmids to overexpress to MET (MET OE) or LINC01510 (LINC01510 OE) for 96 hours. β-ACTIN was used as a loading control. Densitometry values for the representative blots are shown below. (ii) Quantification of MET from three biological replicates as in E(i). F) Expression of (i) MET and (ii) LINC01510 in KMT5C wildtype (WT) cells that were either UT or transfected with the indicated vectors. Data are normalized to GAPDH. G) Erlotinib dose response via SRB assay was evaluated in WT cells that were either UT or that were transfected with the indicated vectors, as described in C. H) Proliferation of WT cells transfected as in G, was evaluated as described in D. I) Model depicting loss of KMT5C in NSCLC results in development of erlotinib resistance via LINC01510-mediated upregulation of MET.