Dysregulation of microRNAs has been demonstrated to contribute to malignant progression of cancers, including hepatocellular carcinoma (HCC). MiR-24-3p was previously reported to be significantly upregulated in HCC. However, the potential role and mechanism of action of miR-24-3p in the initiation and progression of HCC remain largely unknown. Quantitative reverse transcription polymerase chain reaction demonstrated that miR-24-3p was significantly upregulated in HCC tumor tissues compared with nontumor tissues. The cell viability, colony formation assay, and tumorigenicity assays in nude mice showed that miR-24-3p could enhance HCC cell growth in vitro and in vivo. Metallothionein 1M was verified as an miR-24-3p target gene by using dual-luciferase reporter assays, quantitative reverse transcription polymerase chain reaction, and Western blotting, which was involved in miR-24-3p regulated HCC cell growth. These results indicated that miR-24-3p plays an important role in the initiation and progression of HCC by targeting metallothionein 1M, and the miR-24-3p/metallothionein 1M pathway may contribute to the development of novel therapeutic strategies for HCC in the future.

Abstract. MicroRNAs serve a critical role in human hepatocellular carcinoma (HCC) progression. However, the exact role of microRNA-143 (miR-143) in HCC remains unclear. The current study investigates the molecular mechanism of miR-143 in HCC. In cultured HepG2 and Bel7402 cell lines, miR-143 levels were raised by lentivirus transduction. This significantly inhibited HCC progression in terms of cell invasion and proliferation in both HepG2 and Bel7402 cell lines (P<0.05). MiR-143 also significantly decreased tumor implantation in vivo (P<0.05). Regulation of miR-143 on its direct target, GATA-binding factor 6 (GATA6), was investigated by multiple strategies, including dual-luciferase assay, quantitative polymerase chain reaction and western blot analysis. The results indicated that miR-143 was downregulated in both HCC cell lines and human tumors. GATA6 was identified as the downstream target of miR-143 in HCC, and overexpressing GATA6 was able to counter the tumor-suppressive effect of miR-143 on HCC in HepG2 and Bel7402 cells by significantly increasing proliferation and invasion rates (P<0.05). Therefore, a novel epigenetic pathway was identified in which miR-143 may suppress the malignancy of HCC by targeting GATA6.

Affibody‐conjugated RALA (affi‐RA) are designed for delivering oligomeric 5‐fluorodeoxyuridine (FUdR, metabolite of 5‐FU) strand to raise the selectivity of 5‐fluorouracil (5‐FU), decrease its toxicity and improve its suboptimal therapeutic efficacy. The nanodrugs, FUdR@affi‐RA, are spontaneously assembled by electrostatic interaction between positively charged affi‐RA and negatively charged FUdR15‐strands (15 consecutive FUdR). FUdR@affi‐RA exhibits excellent stability under simulated physiological conditions. Compared with free FUdR, FUdR@affi‐RA shows excellent targeting and higher cytotoxicity in human epidermal growth factor receptor 2 (HER2) overexpressing gastric cancer N87 cells. Moreover, the anticancer mechanism studies reveal that FUdR@affi‐RA enhances the expression and activity of apoptosis‐associated proteins in the Bcl‐2/Bax‐caspase 8,9‐caspase 3 apoptotic pathway induced by FUdR. This study indicates that the fusion vector, affi‐RA, presents a promising delivery system platform for nucleoside analogue drugs and provides a new strategy for the development of therapeutics of cancer treatment.

Reagents, materials and instrumentation Reagents were purchased from Shanghai Aladdin Biochemical Technology Co., Ltd. All reagents were AR. H2O was deionized water. NMR (600 MHz) spectra were obtained on Bruker AVANCE III. HRMS were carried out on Bruker, Apex Ultra 7.0T. UV-vis spectra were got at Agilent Cary 60. Fluorescence spectra were gained at Agilent Cary Eclipse. IR was obtained at Thermo Nicolet iS10. Synthesis of the probe Synthesis of compound 2. The synthetic routes of the probe and the control compounds are shown in Scheme 1. Dissolve compound 1 (450 mg), o-phthalic anhydride (296 mg) and

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