RRC ID 85788
著者 Arakawa H, Komatsu S, Kishimoto T, Kamiya H, Ishida R, Takashima Y, Nishibeppu K, Kiuchi J, Imamura T, Ohashi T, Shimizu H, Arita T, Konishi H, Shiozaki A, Kubota T, Fujiwara H, Otsuji E.
タイトル Low levels of tumor suppressor miR-3619 in plasma contribute to malignant outcomes and a target for nucleic acid therapy in esophageal cancer.
ジャーナル Sci Rep
Abstract Recent studies indicate that reduced levels of certain tumor-suppressing microRNAs (miRNAs) circulating in the blood are linked to tumor progression and poor prognosis across various types of malignancies. Identified from a comprehensive analysis of the NCBI and miRNA databases, we tested tumor suppressor miR-3619-5p in esophageal squamous cell carcinoma (ESCC). Both test-scale and large-scale analyses demonstrated that plasma levels of miR-3619-5p were markedly lower in ESCC patients than in healthy volunteers. Lower plasma levels of miR-3619-5p showed a strong association with advanced pathological stages and were recognized as an independent prognostic marker. Overexpression of miR-3619-5p in ESCC cells inhibited cell proliferation, migration and invasion through the direct suppression of novel target protein, proviral insertion site in Moloney murine leukemia virus 1 (PIM1). PIM1 is overexpressed in various solid and hematological cancers including ESCC, and has proven to be a promising target of inhibitors in recent clinical trials. In vivo, increased plasma 3619-5p levels following subcutaneous injection in mice bearing ESCC tumors significantly inhibited tumor growth, with low expression of PIM1 in tumor. Until now, no study has demonstrated that the secretory-type miRNA such as miR- 3619-5p could contribute to nucleic acid therapy to PIM1. Reduced blood levels of miR-3619-5p are linked to ESCC progression and poor prognosis, suggesting that miR-3619-5p could act as a novel therapeutic focus for nucleic acid-based treatment targeting PIM1 in ESCC patients.
巻・号 15(1)
ページ 27358
公開日 2025-7-27
DOI 10.1038/s41598-025-12246-6
PII 10.1038/s41598-025-12246-6
PMID 40717138
PMC PMC12301473
MeSH Animals Biomarkers, Tumor / blood Carcinoma, Squamous Cell* / blood Carcinoma, Squamous Cell* / genetics Carcinoma, Squamous Cell* / pathology Carcinoma, Squamous Cell* / therapy Cell Line, Tumor Cell Movement / genetics Cell Proliferation / genetics Esophageal Neoplasms* / blood Esophageal Neoplasms* / genetics Esophageal Neoplasms* / mortality Esophageal Neoplasms* / pathology Esophageal Neoplasms* / therapy Esophageal Squamous Cell Carcinoma Female Gene Expression Regulation, Neoplastic Humans Male Mice MicroRNAs* / blood MicroRNAs* / genetics Middle Aged Prognosis
IF 3.998
リソース情報
ヒト・動物細胞 TE-5(RCB1949) TE-8(RCB2098) TE-9(RCB1988) TE-15(RCB1951)