Abstract 2167
Background
Continuous effort unraveled GPI pathway that anchors cell surface proteins mediating tumor microenvironment interactions. GPI axis is initiated in breast cancer upon PIG-C elevation which induces MSLN surface expession. MSLN is anti-apoptotic GPI-AP, whose immune therapies yielded tremendous results. CD80 is a unique immunomodulator that binds to CD28, CTLA4 and PDL1. Recombinant GPI-CD80 is evaluated as tumor vaccine. RNAi is a promising tool for immuno-targeted therapy as crucial immuno modulators are blocked. Our aim is to investigate impact of nc-RNAs on MSLN, PIG-C and CD80 for the first time.
Methods
miR-2355, miR-455 and NEAT-1 targeted MSLN, PIG-C and CD80 by bioinformatic analysis. MSLN/CD80 plasmids were transfected in MDA-MB-231 cells, then treated with synthetic nc-RNAs. Surface CD80 and MSLN were assessed by flow cytometry.Gene mRNA level was tested by q-PCR.
Results
PIG-C Silencing, NEAT-1 and miR-2355 elevation, plus NEAT-1/miR-2355 combination droped PIG-C mRNA level signtificantly (p < 0.0001 each) compared to untreated cells and miR-2355 inhibitor (P < 0.0001) miR-2355 elevation significantly droped MSLN mRNA level compared to untreated cells (P < 0.0001) Conversely, miR-2355 inhibitor, NEAT-1 mimic and NEAT-1/miR-2355 combination significantly increased MSLN expression level (P < 0.0001 each). PIG-C siRNA did not have significant effect on MSLN mRNA level PIG-C siRNA and miR-2355 mimic significantly droped MSLN surface level MFI compared to mock (P < 0.0001 each) but miR-2355 inhibitor significantly increased MSLN MFI (P < 0.0001) NEAT-1 mimic and NEAT-1/miR-2355 combination did not have significant effect on MSLN MFI. miR-455 mimic signifincantly droped both surface CD80 MFI and CD80 mRNA level compared to mock (P < 0.0001) Contrastingly, miR-455 inhibitor significantly increased both CD80 MFI and CD80 mRNA level compare to mock (P < 0.0001) NEAT-1 mimic and NEAT-1/miR-455 combination did not show significant effect on CD80 MFI or CD80 mRNA level.
Conclusions
To sum up, our study sheds light on new targets for breast cancer immunotherapy. NEAT-1 is dominant promising sponge for several mi-RNAs which potientiates its role in governing many immunomoduolatory pathways. Our study paves the way for future investigations on the role of NEAT-1 in immuno-targeted therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3524 - Cabazitaxel For Octogenarian Patients With Metastatic Castration-Resistant Prostate Cancer (MCRPC).
Presenter: Paolo Tralongo
Session: Poster Display session 3
Resources:
Abstract
5637 - External Validation of a Prognostic Score in First-Line Metastastic Castration-Resistant Prostate Cancer (mCRPC)
Presenter: David Lorente
Session: Poster Display session 3
Resources:
Abstract
3228 - Treatment outcomes of 3rd treatment in a real-world metastatic castration resistant prostate cancer (mCRPC) population: results from the Dutch CAPRI-registry
Presenter: Jessica Notohardjo
Session: Poster Display session 3
Resources:
Abstract
4695 - Pelvic lymph node dissection and its extent on survival benefit in prostate cancer patients with a risk of lymph node invasion>5%: a propensity score matching analysis from SEER database
Presenter: Junru Chen
Session: Poster Display session 3
Resources:
Abstract
4438 - Multi-institutional evaluation of therapeutic management for oligometastatic cancer prostate recurrence with choline-PET/CT
Presenter: Morgane Guibert-broudic
Session: Poster Display session 3
Resources:
Abstract
4574 - Safety of new androgen receptor inhibitors (ARi) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC): a network meta-analysis of randomized controlled trials (RCT)
Presenter: Amelia Altavilla
Session: Poster Display session 3
Resources:
Abstract
3816 - Real-world use of radium-223 for treatment of metastatic castration resistant-prostate cancer (mCRPC): results from the Dutch CAPRI registry
Presenter: Malou Kuppen
Session: Poster Display session 3
Resources:
Abstract
5180 - A phase 2a study of radium-223 dichloride (Ra-223) alone or in combination with abiraterone acetate or enzalutamide in metastatic castration-resistant prostate cancer (mCRPC)
Presenter: Daniel Petrylak
Session: Poster Display session 3
Resources:
Abstract
1067 - Adding ADT to PSMA-PET/CT-guided SBRT for oligometastatic prostate cancer improves distant progression-free survival
Presenter: Carole Mercier
Session: Poster Display session 3
Resources:
Abstract
5529 - Safety and efficacy of Ac-225-PSMA-617 in metastatic castration resistant prostate cancer (mCRPC) after failure of Lu-177-PSMA
Presenter: Robert Tauber
Session: Poster Display session 3
Resources:
Abstract