Fig 7.

SIRT1-Δ2/9 mRNA is overexpressed in cancer tissues. (A) SIRT1-Δ2/9, SIRT1-FL, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression in paired cancer versus adjacent normal control tissue samples, using 100 ng total RNA from each tissue with primer pairs 2-9F/10R for SIRT1-Δ2/9, SEx4/8Rvs for SIRT1-FL, and GAPDH (primer sequences are shown in Table S1 of the supplemental material). TP53 (exons 5 to 8) was sequenced (Materials and Methods), and details of individual mutations are indicated. wt, wild-type p53; nd, not determined; ∗, deletion from residues 188 to 224. (B) SIRT1-Δ2/9 regulates MMP2. The graph shows levels of MMP2 RNA following siRNA knockdown or overexpression of SIRT1-Δ2/9 in HCT116 cells. ∗, P < 0.05; ∗∗∗, P < 0.001. MMP2 RNA levels were determined by qRT-PCR. (C) Schematic model of SIRT1-Δ2/9 regulation. SIRT1-Δ2/9 mRNA splicing and translation of mRNA into protein are suppressed by p53 and CUGBP2, respectively, while SIRT1-Δ2/9 is required to maintain basal p53 protein levels, thus forming a feedback loop between SIRT1-Δ2/9 and p53.