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

Peixin Dong, Ying Xiong, Jiehai Yu, Lin Chen, Tang Tao, Song Yi, Sharon J.B. Hanley, Junming Yue, Hidemichi Watari, Noriaki Sakuragi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5257-5268
Number of pages12
JournalOncogene
Volume37
Issue number39
DOIs
StatePublished - Sep 27 2018

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Uterine Cervical Neoplasms
Catenins
Wnt Signaling Pathway
Immune Evasion
MAP Kinase Signaling System
Oncogene Proteins
Mitogen-Activated Protein Kinase Kinases
Phosphatidylinositol 3-Kinases
Small Interfering RNA
Neoplasms
Carcinogenesis
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

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.

In: Oncogene, Vol. 37, No. 39, 27.09.2018, p. 5257-5268.

Research output: Contribution to journalArticle

Dong, P, Xiong, Y, Yu, J, Chen, L, Tao, T, Yi, S, Hanley, SJB, Yue, J, Watari, H & Sakuragi, N 2018, 'Control of PD-L1 expression by miR-140/142/340/383 and oncogenic activation of the OCT4–miR-18a pathway in cervical cancer', Oncogene, vol. 37, no. 39, pp. 5257-5268. https://doi.org/10.1038/s41388-018-0347-4
Dong, Peixin ; Xiong, Ying ; Yu, Jiehai ; Chen, Lin ; Tao, Tang ; Yi, Song ; Hanley, Sharon J.B. ; Yue, Junming ; Watari, Hidemichi ; Sakuragi, Noriaki. / Control of PD-L1 expression by miR-140/142/340/383 and oncogenic activation of the OCT4–miR-18a pathway in cervical cancer. In: Oncogene. 2018 ; Vol. 37, No. 39. pp. 5257-5268.
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