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<p>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.</p>

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Low levels of tumor suppressor miR-3619 in plasma contribute to malignant outcomes and a target for nucleic acid therapy in esophageal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月27日

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  • Hiroshi Arakawa,
  • Shuhei Komatsu,
  • Takuma Kishimoto,
  • Hajime Kamiya,
  • Ryo Ishida,
  • Yusuke Takashima,
  • Keiji Nishibeppu,
  • Jun Kiuchi,
  • Taisuke Imamura,
  • Takuma Ohashi,
  • Hiroki Shimizu,
  • Tomohiro Arita,
  • Hirotaka Konishi,
  • Atsushi Shiozaki,
  • Takeshi Kubota,
  • Hitoshi Fujiwara,
  • Eigo Otsuji

摘要

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.