Fig. 2

The roles of IGF2BP1 in promoting and suppressing tumor growth and invasion via regulating different mRNA targets, under the modulation of upstream non-coding RNAs. (1) Some miRNAs/lncRNAs upregulate or downregulate IGF2BP1 expression levels. (2) IGF2BP1 promotes the expression of c-MYC and MKI67 by stabilizing their transcripts and promotes tumor cell proliferation and growth (a, b). In addition, IGF2BP1 elevates CD44 and PTEN expression via preventing mRNA turnover. The enhancement of CD44 expression induces the formation of invadopodia and therefore may promote the tumor cell migration and invasiveness (f, j). Elevation of PTEN inhibits PIP3/PIP2 ratios and then interferes with the activation of RAC1, which enhances cell polarization and thus contributes to directed tumor cell migration as well as tumor invasion (e, j). IGF2BP1 suppresses the expression of MAPK4 and ACTB through interfering with mRNA translation (g, h). The inhibition of MAPK4 antagonizes MK5-directed phosphorylation of HSP27. PHSP27 at both residues induces the degradation of oligomers and increases the sequestering of actin monomers by the phosphorylated protein. The reduced ACTB also decreases G-actin levels. This shifts the cellular G-/F-actin equilibrium contributes to cell adhesion and actin dynamics and finally promotes cell migration velocity (I) [41, 84,85,86, 101, 102]. Furthermore, IGF2BP1 promotes RGS4 expression and thus indirectly depresses tumor cell invasion (d). IGF2BP1 inhibits PTGS2 expression (c). The reduction of PTGS2 indirectly promotes tumor cell invasion and releases the suppression for cell apoptosis (C1, C2) [17]. C-Myc and IGF2BP1 constitute a potential feedback mechanism to reciprocally regulate expression of each other (k) [68]. The hypermethylation of promoter in IGF2BP1 leads to its expression silencing (m) [81, 82].The gray dotted lines show that the interaction of the depicted pathways needs to be explored. The part of Fig. 2 including pathway from (e, f, h, and g to i and j is adapted from the Figure 3 of the paper by Stohr et al. [102]