MiRNA-142-3p increases radiosensitivity in human umbilical cord blood mononuclear cells by inhibiting the expression of CD133

Abstract

This study is to explore the molecular regulation mechanism of CD133 which is associated with malignancy and poor prognosis of blood system diseases. CD133+HUCB-MNC (human umbilical cord blood mononuclear cells) and CD133−HUCB-MNC were isolated and amplificated from umbilical cord blood, and then were exposed to different doses of radiation and subjected to a clonogenic assay. CCK-8 kit was used to detect cell viability, Annexin V-FITC/PI cell apoptosis detection kit was used for the detection of apoptotic cells and the BrdU assay was performed by flow cytometry. The expression of protein was analyzed by western blots. The profile of miRNA expression in response to radiation was examined and validated by RT-PCR. miR-142-3p inhibited the expression of CD133 in umbilical cord blood mononuclear cells to increase radiosensitivity. CD133+HUCB-MNC cells were more radioresistant compared with CD133−HUCB-MNC cells. CD133+HUCB-MNC cells showed higher p-AKT and p-ERK levels after radiation. And miR-142-3p acted on 3′UTR of CD133 mRNA to inhibit CD133 expression. Moreover, miRNA-142-3p mimic increased radiosensitivity in CD133+HUCB-MNC cells. Our results elucidated a novel regulation pathway in hematopoietic stem cells and suggested a potential therapeutic approach for blood system diseases therapy.

The Emerging Role of miRNAs for the Radiation Treatment of Pancreatic Cancer

“…A current literature search reveals an association between the expression of these miRNAs, their targets (e.g., Chk1, c-Myc, ATM and Cyclins) and either radioresistance or radiosensitivity ( Table 2 ) [ 98 , 107 , 113 , 120 ]. Most of these miRNAs (miR-15b, miR-451, miR-186, miR-421, miR-98, miR-142, miR-26b, miR-16, let-7 family) mediate radiosensitivity [ 98 , 105 , 106 , 107 , 108 , 109 , 112 , 113 , 114 , 116 , 117 , 118 , 120 , 121 ] suggesting that the radiation-induced downregulation of these miRNAs might enhance radioresistance.…”

Viability and intracellular nitric oxide generation in the umbilical cord blood CD34+CD133– and CD34+CD133+ cell populations exposed to local anaesthetics

“…Our results indicate that CD34 + CD133 + phenotype present with less pronounced propensity to cell death and are consistent with the resistance to apoptosis of CD133 + phenotype [ 8 , 19 ]. In human UCB MNC subset, CD133 + phenotype showed better radioresistance compared with CD133 – cells with the low radiation induced apoptosis and distinct repair signalling [ 20 ]. Relative insensitivity to apoptosis of UCB progenitors was reported to depend on active upregulation of caspase 8 and NF-κB-related pathway [ 19 ], which in our study analysing UCB cells exposed to inflammatory conditions of natural labour might have been of importance.…”