pgen.1009094.g009.tif (399.7 kB)

In vitro and in vivo functional validation of chromatin remodelers in cuSCC.

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posted on 2021-08-16, 17:39 authored by Aziz Aiderus, Justin Y. Newberg, Liliana Guzman-Rojas, Ana M. Contreras-Sandoval, Amanda L. Meshey, Devin J. Jones, Felipe Amaya-Manzanares, Roberto Rangel, Jerrold M. Ward, Song-Choon Lee, Kenneth Hon-Kim Ban, Keith Rogers, Susan M. Rogers, Luxmanan Selvanesan, Leslie A. McNoe, Neal G. Copeland, Nancy A. Jenkins, Kenneth Y. Tsai, Michael A. Black, Karen M. Mann, Michael B. Mann

Levels of shRNA-mediated knockdown of KMT2C or NCOA2 in human cuSCC cell lines (A) A431 (B) COLO16 or (C) SCC13 cells confirmed by qPCR compared to a non-targeting (NTC) shRNA. Target gene knockdown significantly increases proliferation rates of (D) A431 (shNTC vs. shKMT2C q-value<0.0001; shNTC vs. shNCOA2 q-value = 0.0019; shKMT2C vs. shNCOA2 q = 0.017), (E) COLO16 (shNTC vs. shKMT2C q-value = 0.01; shNTC vs. shNCOA2 q-value = 0.4; shKMT2C vs. shNCOA2 q = 0.06) or (F) SCC13 cells (shNTC vs. shKMT2C q-value = 0.06; shNTC vs. shNCOA2 q-value<0.0001; shKMT2C vs. shNCOA2 q = 0.01); 3 replicates per group; error bars, SEM; statistical significance measured by two-factor ANOVA followed by FDR-corrected q-values for multiple comparisons. KMT2C and NCOA2 knockdown significantly accelerates cuSCC xenograft progression in vivo. (G) A431, corrected P = 0.0488 (shNTC vs. shKMT2C P_FDR = 0.0214; shNTC vs. shNCOA2 P_FDR = 0.0321), (H) COLO16, corrected P<0.0001 (shNTC vs. shKMT2C P_FDR<0.0001; shNTC vs. shNCOA2 P_FDR<0.0001) and (i) SCC13, corrected P = 0.0198 (shNTC vs. shKMT2C P_FDR<0.0275; shNTC vs. shNCOA2 P_FDR = 0.0184). Statistical significance measured by one-way ANOVA followed by multiple pairwise comparisons and FDR-adjusted P-values.