Lin28 is a conserved RNA-binding protein in higher eukaryotes that regulates several important cellular functions related to development, glucose metabolism, differentiation, and pluripotency. Conditional reactivation of the Lin28 gene in adult mice significantly accelerates the wound healing process of injured fingers. This study aimed to investigate the effects of Lin28 gene overexpression on the proliferation of human dental pulp cells (HDPCs) and its mechanisms. The results showed that Lin28 promoted cell proliferation and the S-G2/M transition of HDPCs and directly bound to a set of cell cycle regulatory mRNAs in HDPCs. Through bioinformatics analysis and luciferase assays, the researchers confirmed that let-7a targets IGF2BP2. Silencing IGF2BP2 showed similar cellular and molecular effects as let-7a. Similarly, restoring IGF2BP2 counteracted the effects of let-7a expression. In conclusion, Lin28 promotes cell proliferation by regulating mRNA translation (let-7-independent) and miRNA biogenesis (let-7-dependent). Lin28 can tightly control HDPC proliferation by promoting the expression of pro-proliferative genes by directly enhancing their translation.
Here, it was shown that the levels of Lin28 mRNA and protein in lentivirus-Lin28 (LV-Lin28)-infected HDPCs were significantly increased compared with uninfected HDPCs, while there was little difference between the lentivirus-control (LV-CN)-infected and control groups (Figure 1A). The absorbance data of the CCK-8 assay showed that the cell proliferation of LV-Lin28-infected HDPCs was significantly increased at 48 hours compared with the control cells (Figure 1B). The cell proliferation of LV-Lin28-infected HDPCs was further enhanced at 72 hours. Using EdU detection, it was found that the percentage of EdU-positive cells in LV-Lin28-infected cells was significantly increased compared with the control cells (Figure 1C), indicating that cell viability and cell growth in HDPCs with stable overexpression of Lin28 were significantly promoted. In summary, these results indicate that Lin28 promotes the cell proliferation of HDPCs.
Figure 1. Lin28 promotes the cell proliferation of HDPCs. (Liu Y, et al., 2019)