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- 저자 : Tatsuya Mikami (검색결과 2 건)
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Tatsuya Mikami,Yuta Saeki,Sayaka Hirai,Mayuko Shimokawa,Yukiko Umeyama,Yusaku Kuroda,Hiroaki Kodama 한국식물생명공학회 2018 Plant biotechnology reports Vol.12 No.6
RNA silencing is a sequence-specific form of epigenetic regulation that targets invasive nucleic acids. RNA-dependent RNA polymerase6 (RDR6) converts target RNA molecules, such as transgene transcripts, into double-stranded RNAs (dsRNAs) during posttranscriptional gene silencing (PTGS). Then, these dsRNAs are processed into small RNAs that guide sequencespecific RNA degradation. T-DNA-derived small RNAs are generated during the transfer of T-DNA from Agrobacterium to plant cells and compromise the function of the genes in the T-DNA. In the present study, we produced selection-markerfree transgenic tobacco plants using the MAT vector system, and expression of the tobacco RDR6 gene (NtRDR6) was suppressed using inverted-repeat-induced PTGS. Reduced expression of the NtRDR6 gene improved the transient expression of the transgene in the agroinfiltrated leaves and enhanced the production of hairy roots after infection with Agrobacterium containing a root-inducing T-DNA. The expression level of the sense transgene was determined in individual hairy roots, and knockdown of the NtRDR6 gene did not affect the distribution of the expression levels in individual transformants. These results indicate that NtRDR6 partially inhibited T-DNA function during T-DNA transfer but did not affect the expression of the transgene in stable transformants, except in transformants showing sense-transgene-induced PTGS.
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RUNX1–Survivin Axis Is a Novel Therapeutic Target for Malignant Rhabdoid Tumors
Masamitsu Mikami,Tatsuya Masuda,Takuya Kanatani,Katsutsugu Umeda,Hidefumi Hiramatsu,Hirohito Kubota,Tomoo Daifu,Atsushi Iwai,Etsuko Yamamoto Hattori,Kana Furuichi,Saho Takasaki,Sunao Tanaka,Yasuzumi M 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.12
Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development ofnovel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 (RUNX1) and RUNX1–Baculoviral IAP (inhibitor of apoptosis) Repeat-Containing 5 (BIRC5/survivin) axis in the proliferation of MRT cells, as it can be used as an ideal target for anti-tumor strategies. The mechanism of this reaction can be explained by the interaction of RUNX1 with the RUNX1-binding DNA sequence located in the survivin promoter and its positive regulation. Specific knockdown of RUNX1 led to decreased expression of survivin, which subsequently suppressed the proliferation of MRT cells in vitro and in vivo. We also found that our novel RUNX inhibitor, Chb-M, which switches off RUNX1 using alkylating agent-conjugated pyrrole-imidazole polyamides designed to specifically bind to consensus RUNX-binding sequences (5′-TGTGGT-3′), inhibited survivin expression in vivo. Taken together, we identified a novel interaction between RUNX1 and survivin in MRT. Therefore the negative regulation of RUNX1 activity may be a novel strategy for MRT treatment
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