Fig. 2: BMAL1 promotes growth and survival in ccRCC cells.

Dependency (CHRONOS) scores (A) and correlations thereof (B) for bHLH-PAS members in n = 37 RCC cell lines from DepMap^30,31. Boxplots depict the median and interquartile range (IQR), whiskers extend either to the minimum or maximum data point or 1.5 × IQR beyond the box, whichever is shorter. In (A), p values calculated from multiple paired t tests with HPRT1 as the reference group, adjusted for multiple comparisons using the Holm method, were: BMAL1: 0.001, BMAL2: 0.007, EPAS1: 0.006, HIF1A: 1.47e⁻⁶. Representative images (C) and quantification (D,E) of colonies stained with crystal violet 10–16 days after plating 250 cells expressing the indicated plasmids per well. Data represent the mean ± s.d. for four (D) or three (E) independent experiments, each of which used three wells per condition. *P < 0.05, **P < 0.01, ***P < 0.001 by two-way ANOVA with Tukey’s correction for multiple hypothesis testing. F Volume of xenograft tumors grown in flanks of male or female NIH-III Nude mice from implanted 786O or A498 cells expressing indicated shRNAs. n = 10 xenografts were initiated for each group; up to two xenografts that failed to establish were excluded from analysis for each group. Weekly measurements of individual tumor volumes are shown. ****P < 0.0001 for shBMAL1 vs shControl by linear regression. Details of linear regression statistics: 786 O male: F = 30.13, DFn = 1, DFd = 75; 786O female: F = 41.58, DFn = 1, DFd = 78; A498 male: F = 26.01, DFn = 1, DFd = 96; A498 female: F = 27.02, DFn = 1, DFd = 96. Source data are provided as a Source Data file.