miR-100 inhibits cell proliferation in mantle cell lymphoma by targeting mTOR

Abstract

Background miR-100 is reported to be associated with cell proliferation and apoptosis. However, the function of miR-100 in mantle cell lymphoma (MCL) is unknown. The purpose of this study is to analyze the abnormal expression of miR-100 and mTOR in MCL together with their potential biological function and pathogenesis. Method Eighteen MCL tissue samples and 3 cell lines (Jeko-1, Mino, Granta-519) were investigated in this research study, while eighteen samples of proliferative lymphadenitis from patients and peripheral lymphocyte cells from healthy volunteers served as controls. The expression and alteration of miR-100 and mTOR mRNA were detected by RT-PCR. The expression and alteration of mTOR protein were explored by Western blot. LV-miR-100-up and LV-mTOR-RNAi were constructed and transfected by lentivirus transfection. Cell proliferation, cell apoptosis and the cell cycle were detected using CCK-8 and flow cytometry. Bioinformatics prediction software was used to predict the miR-100 target gene of mTOR. A double luciferase experiment was used to verify miR-100 targeting at the mTOR-3′-UTR. The interaction between miR-100 and mTOR was further studied using recovery experiments. GraphPad Prism 7 software (version 7.2) was used for statistical analysis, and a P value < 0.05 was considered statistically significant. Results We found that the expression of miR-100 mRNA in MCL tissues and cell lines was lower, while that of the mTOR protein was higher. There was a negative correlation between miR-100 and mTOR in both MCL tissues and cell lines. Promoting miR-100 and inhibiting mTOR could inhibit cell proliferation, induce cell apoptosis and block the cell cycle in the G1 phase. A double luciferase reporter assay showed that mTOR was one of the target genes of miR-100. The recovery experiment demonstrated that PV-mTOR-up partially set off the effect of LV-miR-100-up on decreasing mTOR expression, inhibiting proliferation, inducing apoptosis and blocking the cell cycle in G1 phase in both Jeko-1 and Mino cells. Conclusions Abnormal expression of miR-100 and mTOR was found in MCL, which included downregulation of miR-100 and upregulation of mTOR. The expression of mTOR is negatively correlated with miR-100. It may play an important role in MCL pathogenesis. miR-100 up-regulation can inhibit cell proliferation, promote cell apoptosis, and inhibit cell cycle in G1 phase by targeting the mTOR gene. miR-100 may potentially be an anti-mantle cell lymphoma gene.

YTHDF1 promotes hepatocellular carcinoma progression via activating PI3K/AKT/mTOR signaling pathway and inducing epithelial-mesenchymal transition

“…Interestingly, our study also demonstrated that YTHDF1 facilitated HCC cell cycle progression, which was predicted and indicated by previous studies [28,29,36]. The PI3K/AKT/mTOR signaling pathway plays a broad spectrum role in physiology, and its dysregulation often leads to multiple diseases, including cancer [37][38][39][40]. There is evidence that the PI3K/AKT/mTOR pathway mediates the function of m 6 A "writers" METTL3 and METTL14 in the progression of gastric cancer and retinoblastoma [41,42].…”

The diagnostic and prognostic significance of small nuclear ribonucleoprotein Sm D1 aberrantly high expression in hepatocellular carcinoma

“…Yu et al demonstrated that miR-100 up-regulation enhanced cell autophagy and apoptosis induced by cisplatin in osteosarcoma by targeting mTOR [50]. In addition, Lin et al reported that miR-100 inhibits cell proliferation in mantle cell lymphoma by targeting mTOR [51]. Another study revealed that miR-100 promotes the autophagy of hepatocellular carcinoma cells by inhibiting the expression of the mTOR pathway [52].…”

Role of microRNAs in B-Cell Compartment: Development, Proliferation and Hematological Diseases

“…The cluster miR-106a~363, which is composed of microRNAs -18b, -19b-2, -20b, -92a-2, -106a, and -363, appears to function in cell proliferation in the same way as paralogous miR-17-92 cluster, but this remains to be elucidated [ 126 ]. Moreover, miR-100 inhibits cell proliferation by targeting mTOR [ 127 ], miR-15a/16-1 cluster is downregulated in MCL patients and interferes in cell cycle regulation by CCND1, which is a direct target of these two microRNAs [ 128 ] and the miR-29 family also have participation in regulating MCL cell proliferation, regulating cyclins expression [ 129 , 130 , 131 ].…”