並列タイトル等Impact of Oncogenic Targets Controlled by Tumor-Suppressive miR-30a-5p in Pancreatic Ductal Adenocarcinoma
学位博士(医学)
Doctor of Philosophy in Medical Science
一般注記博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨
Background/Aim: Our recent miRNA analyses revealed that miR-30a-5p has tumor-suppressive activity in pancreatic ductal adenocarcinoma (PDAC). Herein, we sought to identify tumor-suppressive genes controlled by miR-30a-5p, emphasizing on genes that are closely involved in the molecular pathogenesis of PDAC. We uncovered several novel findings regarding the pathogenesis of this disease. Materials and Methods: In silico analyses were used to identify the putative target genes of miR-30a-5p and assess their expression levels. Direct regulation of RRM2 by miR-30a-5p and its oncogenic functions were evaluated in PDAC cell lines. Overexpression of RRM2 was demonstrated in clinical samples. Results: A total of 24 putative targets were identified by in silico database analysis. High expression of 4 genes (CBFB, RRM2, AHNAK, and DCBLD1) was significantly associated with shorter survival of patients with PDAC. Functional assays demonstrated that knockdown of RRM2 attenuated the malignant phenotype of PDAC cells. Conclusion: The miR-30a-5p/RRM2 axis facilitated the malignant transformation of PDAC cells.PRAMOD NEPAL, YUTO HOZAKA, TAKAKO TANAKA, MASUMI WADA, SHUNICHI ASAI, CHIKASHI MINEMURA, TETSUYA IDICHI, TAKAAKI ARIGAMI, HIROSHI KURAHARA, NAOHIKO SEKI and TAKAO OHTSUKAImpact of Oncogenic Targets Controlled by Tumor-Suppressive miR-30a-5p in Pancreatic Ductal AdenocarcinomaANTICANCER RESEARCH 41: 4821-4836 (2021)https://doi.org/10.21873/anticanres.15297
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