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
Hydrazine is an important raw material in medicine and chemical industry. However, N2H4 is very harmful to the environment and human body. Therefore, the detection of hydrazine is particularly important. In this report, a new type of fluorescence probe based on synergistic effect was developed for the detection of N2H4. The fluorescence of the probe was doubly inhibited by the PET (photo‐induced electron transfer) process and the bridled ESIPT (excited‐state intramolecular proton transfer) process. Upon addition of hydrazine, the interrupted PET process and restored ESIPT worked together leading to the fluorescence enhancement. The probe has good specificity for hydrazine. The LOD (limit of detection) was calculated to be 1.45 ppb (0.045 μM) and the linear range was 0.2‐40.0 μM. The contrast experiment showed that the synergistic effect could improve the sensitivity of the probe to hydrazine. In addition, the probe could be used for the quantitative determination of hydrazine in tap water.
Hepatocellular carcinoma (HCC) metastases in the mediastinum are rare, particularly under the arch of the aorta. The present study describes the case of a 30-year-old male patient who presented with back pain and hoarseness for 2 months due to lymph node metastasis of HCC. The patient had undergone right hepatic lobectomy for HCC 2 years prior and received transarterial chemoembolization 4 times following resection. A computed tomography scan revealed enlarged lymph nodes under the arch of the aorta that appeared to have invaded the left recurrent laryngeal nerve, causing the hoarseness. Percutaneous aspiration biopsy of the enlarged, right supraclavicular lymph node identified malignant cells consistent with HCC. Radiation administered as a therapy to treat for the metastatic lymph nodes did not diminish the tumor but relieved the symptoms.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.