PD-L1 Inhibitor Regulates the miR-33a-5p/PTEN Signaling Pathway and Can Be Targeted to Sensitize Glioblastomas to Radiation

Frontiers in Oncology
Wenzheng XiaShiting Li

Abstract

Glioblastoma (GBM) is the most common and lethal brain tumor in adults. Ionizing radiation (IR) is a standard treatment for GBM patients and results in DNA damage. However, the clinical efficacy of IR is limited due to therapeutic resistance. The programmed death ligand 1 (PD-L1) blockade has a shown the potential to increase the efficacy of radiotherapy by inhibiting DNA damage and repair responses. The miR-33a-5p is an essential microRNA that promotes GBM growth and self-renewal. In this study, we investigated whether a PD-L1 inhibitor (a small molecule inhibitor) exerted radio-sensitive effects to impart an anti-tumor function in GBM cells by modulating miR-33a-5p. U87 MG cells and U251 cells were pretreated with PD-L1 inhibitor. The PD-L1 inhibitor-induced radio-sensitivity in these cells was assessed by assaying cellular apoptosis, clonogenic survival assays, and migration. TargetScan and luciferase assay showed that miR-33a-5p targeted the phosphatase and tensin homolog (PTEN) 3' untranslated region. The expression level of PTEN was measured by western blotting, and was also silenced using small interfering RNAs. The levels of DNA damage following radiation was measured by the presence of γ-H2AX foci, cell cycle, and the ...Continue Reading

References

Nov 6, 2001·Journal of Neuroimmunology·B BadieJ Vorpahl
May 18, 2007·Annual Review of Cell and Developmental Biology·Natascha Bushati, Stephen M Cohen
Nov 3, 2007·Genes & Development·Frank B FurnariWebster K Cavenee
May 3, 2008·The Lancet Oncology·Dieta BrandsmaMartin J van den Bent
Aug 1, 2008·Nature·Daehyun BaekDavid P Bartel
Apr 14, 2010·Cancer Cell·Ruihuan ChenHeidi S Phillips
May 7, 2010·CA: a Cancer Journal for Clinicians·Erwin G Van MeirJeffrey J Olson
Dec 3, 2010·The Journal of Pathology·Thalia A FaraziThomas Tuschl
Apr 3, 2012·Cell·Chi V Dang
Oct 23, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniel S ChenF Stephen Hodi
Apr 27, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Laura Biddlestone-ThorpeKristoffer Valerie
Sep 10, 2014·The Journal of Clinical Investigation·Hui WangXiao-Fan Wang
Aug 19, 2015·Cancer Research·Jasmine LauAnders I Persson
Sep 2, 2015·The Journal of Clinical Investigation·Lieping Chen, Xue Han
Oct 31, 2015·Neuro-oncology·Edjah K NduomAmy B Heimberger
Dec 30, 2016·Nature Reviews. Clinical Oncology·Guido ReifenbergerMichael Weller
Feb 14, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Karolina WoronieckaPeter E Fecci
Mar 30, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Karolina I WoronieckaPeter E Fecci
Jul 20, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yanting GuZhou Zhang
Dec 1, 2018·Cancer Research·Meredith A Morgan, Christine E Canman
Jun 21, 2019·Journal of Immunotherapy·Jizhuang WangWeibin Zhang

❮ Previous
Next ❯

Citations

Mar 5, 2021·Frontiers in Oncology·Thamiris Becker ScheffelFernanda Bueno Morrone
Dec 1, 2021·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Michael ZhangHeike E Daldrup-Link

❮ Previous
Next ❯

Datasets Mentioned

BETA
E-MTAB-9007

Methods Mentioned

BETA
flow cytometry
Reverse-Transcription
Assay
transfection
fluorescence microscopy
Fluorescence
PCR

Software Mentioned

Cell Quest
SPSS
TargetScan
Quantity One

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Related Papers

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Xin Yao QiuXiao Qian Chen
Cancer Immunology Research
Elizabeth A MittendorfGheath Alatrash
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Yawei LiuShohreh Issazadeh-Navikas
© 2022 Meta ULC. All rights reserved