| RRC ID |
85788
|
| Author |
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.
|
| Title |
Low levels of tumor suppressor miR-3619 in plasma contribute to malignant outcomes and a target for nucleic acid therapy in esophageal cancer.
|
| Journal |
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.
|
| Volume |
15(1)
|
| Pages |
27358
|
| Published |
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
|
| Resource |
| Human and Animal Cells |
TE-5(RCB1949)
TE-8(RCB2098)
TE-9(RCB1988)
TE-15(RCB1951) |
