MicroRNA-375 represses tumor angiogenesis and reverses resistance to sorafenib in hepatocarcinoma.

Sorafenib was originally identified as an inhibitor of multiple oncogenic kinases and remains the first-line systemic therapy for advanced hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) have been reported to play critical roles in the initiation, progression, and drug resistance of HCC. In this study, we aimed to identify sorafenib-induced miRNAs and demonstrate their regulatory roles. First, we identified that the expression of the tumor-suppressive miRNA miR-375 was significantly induced in hepatoma cells treated with sorafenib, and miR-375 could exert its antiangiogenic effect partially via platelet-derived growth factor C (PDGFC) inhibition. Then, we demonstrated that sorafenib inhibited PDGFC expression by inducing the expression of miR-375 and a transcription factor, achaete-scute homolog-1 (ASH1), mediated the induction of miR-375 by sorafeinb administration in hepatoma cells. Finally, we verified that the expression of miR-375 was reduced in sorafenib-resistant cells and that the restoration of miR-375 could resensitize sorafenib-resistant cells to sorafenib partially by the degradation of astrocyte elevated gene-1 (AEG-1). In conclusion, our data demonstrate that miR-375 is a critical determinant of HCC angiogenesis and sorafenib tolerance, revealing a novel miRNA-mediated mechanism underlying sorafenib treatment.

Top-Down Integration of Molybdenum Disulfide Transistors with Wafer-Scale Uniformity and Layer Controllability.

The lack of stable and efficient techniques to synthesize high-quality large-area thin films is one of the major bottlenecks for the real-world application of the 2D transition metal dichalcogenides. In this work, the growth of molybdenum disulfide (MoS2 ) on sapphire substrates by sulfurizing the MoO3 film deposited by atomic layer deposition (ALD) is reported. The advantages of the ALD method can be well inherited, and the synthesized MoS2 films exhibit excellent layer controllability, wafer-scale uniformity, and homogeneity. MoS2 films with desired thickness can be obtained by varying MoO3 ALD cycles. The atomic force microscope and Raman measurements demonstrate that the ALD-based MoS2 has good uniformity. Clear Raman shift as a function of the film thickness is observed. Field-effect transistor devices are fabricated through a transfer-free and top-down process. High On/Off current ratio (≈104 ) and medium-level electron mobilities (≈0.76 cm2 V-1 s-1 for monolayer, and 5.9 cm2 V-1 s-1 for four-layer) are obtained. The work opens up an attractive approach to realize the application of wafer-scale 2D materials in integrated circuits and systems.