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Poster Display session

429 - PIG-C and SOCS3: Potential immunotargets regulated by non-coding RNAs in TNBC

Date

14 Dec 2018

Session

Poster Display session

Presenters

Monica Armanios

Citation

Annals of Oncology (2018) 29 (suppl_10): x24-x38. 10.1093/annonc/mdy487

Authors

M.M. Armanios1, R. Abdel Tawab2, H.M. El Tayebi1

Author affiliations

  • 1 Genetic Pharmacology Research Group, Department Of Pharmacology And Toxicology, German University in Cairo, 11835 - Cairo/EG
  • 2 Surgical Oncology, Ain Shams University, 123 - Cairo/EG
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Resources

Abstract 429

Background

Among the crucial proteins having dual role in cancer and immunity is suppressor of cytokine-signaling3 (SOCS3) protein regulating JAK/STAT and IL 6/STAT3/NF-κB pathways, respectively. Another pivotal membrane anchoring protein; PIG-C, that anchors several proteins involved in carcinogenesis. Previous studies proved that miR-34a regulates PDL1. Also, our previous work proved that lncRNAs XIST and TSIX were able to manipulate PDL1 expression in triple negative breast cancer (TNBC). Therefore, this study aims at studying the impact of miR-34a, XIST/TSIX on SOCS3 and PIGC as novel targets to be added to the picture of molecular targeted immunotherapy.

Methods

Twenty pairs of BC tissues and adjacent non-BC tissues were collected from patients undergoing tumor resection surgery. MDA-MB-231 cell line was cultured, transfected for manipulation of gene expression purposes. Total RNA was extracted using Biozol followed by reverse transcription cDNA synthesis, amplification and quantification using quantitative-real-time PCR.

Results

PIG-C was up-regulated in BC compared to controls (p = 0.0017). MiR-34a decreased PIG-C expression in BC cells lines (p < 0.0001) while anti-miR-34a increased PIG-C (p = 0.0259). MiR-34a increased SOCS3 (p = 0.0192) while anti-miR-34a decreased SOCS-3 (p = 0.0003). Upon XIST knockdown, PIG-C was up-regulated (p = 0.0243) and surprisingly SOCS3 was also up-regulated (p = 0.0092). Oppositely, siTSIX decreased PIG-C (p = 0.0320) and it significantly decreased SOCS3 (p = 0.0005) ensuring the previous results with siXIST. Co-transfection of miR-34a and siXIST decreased PIGC (p < 0.0001). Similarly, PIG-C decreased upon co-transfection of miR-34a and siTSIX (p < 0.0001). SOCS3 increased upon co-transfection of miR-34a with siTSIX (p = 0.0017). Synergistically, SOCS3 increased in the cells co-transfected with miR-34a and siXIST (p = 0.0201).

Conclusions

Here, PIG-C and SOCS3 are introduced as new immunotargets in TNBC. In the context of epigenetic regulation, the cross-talk between non-coding RNAs revealed miR-34a to have the lead over XIST and TSIX in regulating PIG-C and SOCS3. These data pave the road for establishing new proteins for molecular targeted immunotherapy along with their key upstream non-coding RNA regulators.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

German University in Cairo, Egypt.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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