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Purpose We investigated whether a 99m Tc radiolabeled anti-miRNA-155 oligonucleotide (AMO-155) could visualize the expression of miR-155 in multiple kinds of tumors in vivo . Methods AMO-155 was chemically synthesized and modified with 2′- O -methyl (2′-OMe) and phosphorothioate (PS). It was radiolabeled with 99m Tc via the conjugation with NHS-MAG3 at 5′ end. The characterization of radiolabeling and serum stability was evaluated using high performance liquid chromatography (HPLC) and agarose gel electrophoresis. The expression of C/EBPβ, one of the miR-155 target proteins, was assessed using Western blot. The cellular uptake and delivery of AMO-155 was further evaluated in tumor cells. 99m Tc-AMO-155 was tested in vivo in multiple tumor models, including miR-155 over-expressed and low-expressed tumor models. Finally, biodistribution of 99m Tc-AMO-155 was evaluated. Results 99m Tc-AMO-155 was prepared with high yield and radiochemical purity. It showed high stability in fresh human serum for 10 h. 99m Tc-AMO-155 displayed comparable capacity as unlabeled AMO-155 to increase the expression of C/EBPβ protein in MCF-7 cells. 99m Tc-AMO-155 showed an increased radioactive uptake in MCF-7 cells after 8 h of incubation, whereas no change of 99m Tc-pertechnetate uptake was observed. Carboxyfluorescein (FAM) labeled AMO-155 had higher fluorescent delivery than Control in HeLa and HepG2 cells by confocal microscopy. In miR-155 over-expressed tumor models, 99m Tc-AMO-155 showed significantly higher tumor accumulation than 99m Tc-Control. Furthermore, 99m Tc-AMO-155 was capable of discriminating between MCF-7 and MDA-MB-231 tumors based on their expression of miR-155. Conclusions Our study successfully prepared and proved 99m Tc-AMO-155 as a prospective imaging agent for the noninvasive visualization of miR-155 expression in vivo . [ABSTRACT FROM AUTHOR]

Highlights: [•] miR-30a represses Eya2 expression by binding to the 3′-untranslated region of Eya2. [•] The miR-30a/EYA2 axis regulates breast cancer cell proliferation and migration. [•] The miR-30a/EYA2 axis modulates G1/S cell cycle progression. [•] The miR-30a/EYA2 axis is dysregulated in breast cancer patients. [ABSTRACT FROM AUTHOR]

Summary Aerobic glycolysis (the Warburg effect) facilitates tumor growth, and drugs targeting aerobic glycolysis are being developed. However, how the Warburg effect is directly regulated is largely unknown. Here we show that transcription factor SIX1 directly increases the expression of many glycolytic genes, promoting the Warburg effect and tumor growth in vitro and in vivo . SIX1 regulates glycolysis through HBO1 and AIB1 histone acetyltransferases. Cancer-related SIX1 mutation increases its ability to promote aerobic glycolysis and tumor growth. SIX1 glycolytic function is directly repressed by microRNA-548a-3p, which is downregulated, inversely correlates with SIX1, and is a good predictor of prognosis in breast cancer patients. Thus, the microRNA-548a-3p/SIX1 axis strongly links aerobic glycolysis to carcinogenesis and may become a promising cancer therapeutic target. [ABSTRACT FROM AUTHOR]