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Your search keyword '"Akihiro Hirao"' showing total 2 results
Start Over Author "Akihiro Hirao" Publisher mdpi ag
2 results on '"Akihiro Hirao"'

1. MiR-125b-5p Is Involved in Sorafenib Resistance through Ataxin-1-Mediated Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

Author

Misato Hirata, Tomoyuki Kawaguchi, Hironori Wada, Tetsuji Takayama, Akihiro Hirao, Hironori Tanaka, Tatsuya Taniguchi, Toshihito Tanahashi, Masahiro Bando, Hiroshi Miyamoto, Yoshifumi Kida, Kensei Nishida, Yasushi Sato, Tetsu Tomonari, Naoki Muguruma, Takahiro Tanaka, and Koichi Okamoto

Subjects
Sorafenib, Cancer Research, Population, Vimentin, Article, ataxin-1, Cancer stem cell, microRNA, medicine, Epithelial–mesenchymal transition, education, RC254-282, education.field_of_study, drug resistance, biology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, hepatocellular carcinoma, Transfection, miR-125b-5p, medicine.disease, digestive system diseases, Oncology, Hepatocellular carcinoma, Cancer research, biology.protein, sorafenib, medicine.drug
Abstract

The mechanism of resistance to sorafenib in hepatocellular carcinoma (HCC) remains unclear. We analyzed miRNA expression profiles in sorafenib-resistant HCC cell lines (PLC/PRF5-R1/R2) and parental cell lines (PLC/PRF5) to identify the miRNAs responsible for resistance. Drug sensitivity, migration/invasion capabilities, and epithelial-mesenchymal transition (EMT) properties were analyzed by biochemical methods. The clinical relevance of the target genes to survival in HCC patients were assessed using a public database. Four miRNAs were significantly upregulated in PLC/PRF5-R1/-R2 compared with PLC/PRF5. Among them, miR-125b-5p mimic-transfected PLC/PRF5 cells (PLC/PRF5-miR125b) and showed a significantly higher IC50 for sorafenib compared with controls, while the other miRNA mimics did not. PLC/PRF5-miR125b showed lower E-cadherin and higher Snail and vimentin expression—findings similar to those for PLC/PRF5-R2—which suggests the induction of EMT in those cells. PLC/PRF5-miR125b exhibited significantly higher migration and invasion capabilities and induced sorafenib resistance in an in vivo mouse model. Bioinformatic analysis revealed ataxin-1 as a target gene of miR-125b-5p. PLC/PRF5 cells transfected with ataxin-1 siRNA showed a significantly higher IC50, higher migration/invasion capability, higher cancer stem cell population, and an EMT phenotype. Median overall survival in the low-ataxin-1 patient group was significantly shorter than in the high-ataxin-1 group. In conclusion, miR-125b-5p suppressed ataxin-1 and consequently induced Snail-mediated EMT and stemness, leading to a poor prognosis in HCC patients., The mechanism of resistance to multikinase inhibitors in hepatocellular carcinoma (HCC) remains unclear. We analyzed miRNA expression profiles in sorafenib-resistant HCC cell lines (PLC/PRF5-R1/R2) and parental cell lines (PLC/PRF5) to identify the responsible miRNAs and target genes involved in the mechanism of resistance. Four miRNAs were significantly upregulated. Among them, we found that miR-125-5p induced sorafenib resistance in HCC cells and in a mouse model. We also revealed that miR-125-5p suppressed ataxin-1 as a target gene and consequently induced Snail-mediated epithelial-mesenchymal transition (EMT) and cancer stemness. Moreover, we demonstrated that ataxin-1 expression has an impact on the prognosis of patients with HCCs. In the future, by comparing the expression status of miR-125b-5p/ataxin-1 and the effect of sorafenib in the clinical setting, it is expected that miR-125b-5p will be established as an effective drug selection marker for treatment selection in patients with HCC.

Published
2021
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2. Giant Wrinkles on the Surface of Epitaxial BaTiO3 Thin Films with Drastic Shrinkage during Transfer from a MgO(100) Single-Crystal Substrate to a Flexible Polyethylene Terephthalate Sheet

Author

Hiroaki Nishikawa, Shinji Umatani, Tomofumi Mizuyama, Akihiro Hiraoka, and Katsuhiro Mikami

Subjects
giant wrinkle, shrinkage, transfer process, BaTiO3, flexible device, Chemical technology, TP1-1185
Abstract

The transfer of ferroelectric and piezoelectric BaTiO3 epitaxial thin films from an original MgO(100) single-crystal substrate to a polyethylene terephthalate (PET) sheet has been studied to fabricate flexible epitaxial functional oxides. The outline of our previous transfer process is as follows: the epitaxial BaTiO3 thin films were deposited on the MgO(100). Then, the surface of the BaTiO3 was adhered onto a PET sheet. Finally, only the MgO(100) substrate was dissolved in a phosphoric aqueous solution, which resulted in the transfer of the epitaxial BaTiO3 thin film from the MgO(100) to a PET sheet. To establish this transfer process, our aim was to prevent any damage, such as cracks and exfoliation, during the transfer of the epitaxial functional oxides. We found that a Pt buffer layer with a ductile nature was effective for improving the quality of transferred epitaxial BaTiO3 thin films. Moreover, the epitaxial BaTiO3 thin films showed a drastic shrinkage of ca. 10%. The surfaces of the shrunk, epitaxial BaTiO3 thin films showed giant wrinkles with a micrometer-order amplitude and a 10-μm-order periodicity without any damage. The epitaxial BaTiO3 thin films with giant wrinkles, accompanied by drastic shrinkage, are similar to the thin films that are coated on a pre-stretched elastomer, which is one of the fabrication processes of stretchable devices.

Published
2021
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