MicroRNA‑29‑3p regulates the β‑catenin pathway by targeting IGF1 to inhibit the proliferation of prolactinoma cells

Abstract

The present study aimed to analyze the effects and underlying mechanisms of microRNA (miR)-29-3p on the proliferation and secretory abilities of prolactinoma cells by targeting insulin-like growth factor (IGF)-1/β-catenin. The relationship between miR-29a-3p and the survival of prolactinoma cells was analyzed with the Kaplan-Meier method in reference to The Cancer Genome Atlas. The expression levels of miR-29a-3p and IGF-1 in MMQ and GH3 cells were detected. A dual-luciferase reporter gene assay was performed to verify the combination of miR-29a-3p and IGF-1. Cells were transfected with a miR-29a-3p mimic and/or IGF-1 pcDNA3.1 to analyze the effects on the proliferation, apoptosis and secretion of prolactin (PRL) and growth hormone (GH) of prolactinoma cells. The effects on β-catenin in the cytoplasm and nucleus were investigated by western blot analysis. The results showed that miR-29a-3p expression was low in MMQ and GH3 cells. Overexpression miR-29a-3p inhibited IGF-1 mRNA and protein expression. miR-29a-3p inhibited cell proliferation and PRL and GH expression, and promoted apoptosis by inhibiting IGF-1. Increasing the expression of miR-29a-3p increased β-catenin levels in the cytoplasm, whereas IGF-1 promoted β-catenin activation and entry into the nucleus, and reversed the inhibitory effects of miR-29a-3p on β-catenin. To conclude, miR-29a-3p inhibited the proliferation and secretory abilities of prolactinoma cells by inhibiting nuclear translocation of β-catenin via a molecular mechanism that is inseparable from IGF-1.

Circular RNA circUSP13 sponges miR‐29c to promote differentiation and inhibit apoptosis of goat myoblasts by targeting IGF1

“…Intriguingly, we found that miR‐29c dramatically reduced the expression level of IGF1 among five candidate mRNAs in goat myoblasts (Figure S5C, p < .01). Correspondingly, knockdown and overexpression of circUSP13 significantly decreased and increased the expression of IGF1 (Figure S5D,E, p < .01, respectively), a well‐established regulator of myoblasts proliferation and differentiation 26,27 . Based on these findings, IGF1 could be considered as a potential target gene for miR‐29c in goat myogenesis.…”

“…IGF1 is an insulin-related peptide that stimulates both proliferation and differentiation of myocytes during myogenesis. 26,27,45 IGF1 regulates myostatin transcription by activating the transcription of nuclear factor of activated T-cells (NFAT) in an IP3/calcium-dependent manner and IGF-1 signaling via the activation of the PI3K/Akt pathway has been well characterized. 46,47 Moreover, inhibiting the IGF1/PI3K/AKT signaling pathway during the differentiation phase of myoblasts impeded the muscle-specific gene expression, preventing satellite cell fusion into myotubes.…”

“…IGF1 is an insulin‐related peptide that stimulates both proliferation and differentiation of myocytes during myogenesis 26,27,45 . IGF1 regulates myostatin transcription by activating the transcription of nuclear factor of activated T‐cells (NFAT) in an IP3/calcium‐dependent manner and IGF‐1 signaling via the activation of the PI3K/Akt pathway has been well characterized 46,47 …”

“…Intriguingly, we found that miR-29c dramatically reduced the expression level of IGF1 among five candidate mRNAs in goat myoblasts (Figure S5C, p < .01). Correspondingly, knockdown and 26,27 Based on these findings, IGF1 could be considered as a potential target gene for miR-29c in goat myogenesis. We then constructed IGF1 3′ UTR wild (IGF1 W ) and mutant (IGF1 M ) luciferase reporter vectors that contain potential miR-29c binding sites (Figure 7A); these two plasmids were transfected separately into 293T/17 cells with miR-29c mimic or NC mimic.…”

Human Bone Marrow Mesenchymal Stem Cell (hBMSCs)-Derived miR-29a-3p-Containing Exosomes Impede Laryngocarcinoma Cell Malignant Phenotypes by Inhibiting PTEN

“…Downregulated miR-29a-3p might account for the tumor promotion of the lncRNA KCNQ1OT1 in hepatocellular carcinoma [30]. In addition, miR-29a-3p was also shown to inhibit the proliferative ability of prolactinoma cells via modulating the β-catenin signaling pathway [31]. Although the oncogenic role of this miRNA in laryngocarcinoma has been reported, its deliver from hBMSCs and the complex mechanisms remains unclear.…”