Control of PD-L1 expression by miR-140/142/340/383 and oncogenic activation of the OCT4–miR-18a pathway in cervical cancer

• Dong, Peixin

• Xiong, Ying

• Yu, Jiehai

• Chen, Lin

• Tao, Tang

• Yi, Song

• Hanley, Sharon J.B.

• Yue, Junming

• Watari, Hidemichi

• Sakuragi, Noriaki

抄録

PD-L1, a key inhibitory immune receptor, has crucial functions in cancer immune evasion, but whether PD-L1 promotes the malignant properties of cervical cancer (CC) cells and the mechanism by which PD-L1 is regulated in CC remains unclear. We report that PD-L1 is overexpressed in CC, and shRNA-mediated PD-L1 depletion suppresses the proliferation, invasion, and tumorigenesis of CC cells. Loss of miR-140/142/340/383 contributes to PD-L1 upregulation. miR-18a enhances PD-L1 levels by targeting PTEN, WNK2 (ERK1/2 pathway inhibitor), and SOX6 (Wnt/β-catenin pathway inhibitor and p53 pathway activator) to activate the PI3K/AKT, MEK/ERK, and Wnt/β-catenin pathways and inhibit the p53 pathway, and miR-18a also directly suppresses the expression of the tumor suppressors BTG3 and RBSP3 (CTDSPL). miR-18a overexpression in CC cells is triggered by OCT4 overexpression. Our data implicate PD-L1 as a novel oncoprotein and indicate that miR-140/142/340/383 and miR-18a are key upstream regulators of PD-L1 and potential targets for CC treatment.

収録刊行物

• Oncogene

  Oncogene 37 (39), 5257-5268, 2018-09-27

  Nature Publishing Group

キーワード

• Cancer Research
• Genetics
• Molecular Biology

詳細情報

• CRID: 1050001202674764672
• NII論文ID: 120006523747
• DOI: 10.1038/s41388-018-0347-4
• ISSN: 14765594
• ISSN: 09509232
• HANDLE: 2115/71539
• Web Site: http://www.nature.com/articles/s41388-018-0347-4
• Web Site: http://www.nature.com/articles/s41388-018-0347-4.pdf
• 本文言語コード: en
• 資料種別: journal article
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