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MicroRNA-140 suppresses osteosarcoma tumor growth by enhancing anti-tumor immune response and blocking mTOR signaling.

Abstract：

:Immune checkpoint blockade is proved to be a promising therapeutic strategy against several human malignancies. MicroRNAs (miRNAs) are ∼22 nucleotide RNAs that play important roles in regulating gene expression, either suppressing its translation or speeding up its degradation. In this study, we demonstrated that miR-140 acts as a critical modulator of PD-L1 and is significantly reduced in osteosarcoma (OS). MiR-140 was inversely correlated with PD-L1 and luciferase reporter assay confirmed that miR-140 can direct regulate PD-L1 expression by binding to its 3'UTR. MiR-140 failed to influence tumor growth in nude mice, whereas markedly inhibited tumor growth in the immune-competent C57BL/6J mice. Mechanistically, the tumor-suppressive role of miR-140 was associated with the increased infiltrates of cytotoxic CD8+ T cells and the decreased infiltrates of myeloid-derived suppressive cells and regulatory T cells. Moreover, miR-140 significantly inhibited mTOR signaling and combined miR-140 overexpression with pharmacological inhibition of mTOR signaling showed remarkable synergistic anti-tumor effect. Collectively, our findings indicate that miR-140 exerts anti-OS efficacy by targeting immune checkpoint molecule PD-L1 and can be developed as a novel immunotherapeutic agent for the treatment of OS.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Ji X,Wang E,Tian F

doi

10.1016/j.bbrc.2017.11.120

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

1342-1348

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(17)32299-4

journal_volume

495

pub_type

杂志文章

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