253P - The role of MiR-221 in regulating gastric cancer radiation sensitivity

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Gastric Cancer
Translational Research
Presenter Guichao Li
Citation Annals of Oncology (2016) 27 (suppl_9): ix68-ix85. 10.1093/annonc/mdw582
Authors G. Li, Y. Deng, L. Liang
  • Radiation Oncology, Fudan University Shanghai Cancer Center, 200032 - Shanghai/CN

Abstract

Background

The purpose of this study was to define the roles of miR-221 in determining sensitivity of gastric cancer to radiation therapy, to explore the underlying mechanism and to evaluate the potential of miR-221 as a biomarker for predicting radio-sensitivity.

Methods

Tumor specimens from 8 patients with a histological diagnosis of gastric adenocarcinoma (stage IIIB/IIIC) which was unrescectable under original evaluation were used in the micro-RNA profiling and comparison. And these specimens were from our phase II study (NCT02024217). These patients never received any chemotherapy before radiation therapy. Human gastric cancer cell lines, MGC-803 and MKN28, were used in vitro (cell culture) studies. Transfection of tumor cells with the mimic or inhibitor of miR-221, and reporter gene assay, were performed to investigate the role of miR-221 in determining radio-sensitivity and the target gene.

Results

Higher expression of miR-221 was observed in human gastric cancer specimens and cell lines that were insensitive to radiation therapy, as compared with sensitive cancer specimens and the cell lines. We also found that miR-221 negatively regulated the expression of PTEN. The role of miR-221 in conferring cellular resistance to radiation treatment was validated in cell culture models. The effect of miR-221 on radio-resistance was mediated through targeting the 3'-UTR of PTEN gene.

Conclusions

The expression level of miR-221 in gastric cancer may serve as a biomarker for sensitivity to radiation therapy, and targeting miR-221 may mean a new approach to sensitizing gastric cancer to radiation treatment.

Clinical trial indentification

Legal entity responsible for the study

N/A

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.