Screening of MicroRNA Related to Irradiation Response and the Regulation Mechanism of miRNA-96-5p in Rectal Cancer Cells.

Fengpeng Wu,Shuguang Ren,Yafan Yang,Congrong Yang,Xiaoxiao Zhang,Guiying Wang,Jun Wang,Chaoxi Zhou,Bingyue Wu

doi:10.3389/fonc.2021.699475

Abstract

Neoadjuvant chemoradiotherapy has been widely used in the treatment of locally advanced rectal cancer due to the excellent advantages of irradiation in cancer therapy. Unfortunately, not every patient can benefit from this treatment, therefore, it is of great significance to explore biomarkers that can predict irradiation sensitivity. In this study, we screened microRNAs (miRNAs) which were positively correlated with irradiation resistance and found that miRNA-552 and miRNA-183 families were positively correlated with the irradiation resistance of rectal cancer, and found that high expression of miRNA-96-5p enhanced the irradiation resistance of rectal cancer cells through direct regulation of the GPC3 gene and abnormal activation of the canonical Wnt signal transduction pathway. Based on the radioreactivity results of patient-derived xenograft models, this is the first screening report for radio-resistant biomarkers in rectal cancer. Our results suggest that miRNA-96-5p expression is an important factor affecting the radiation response of colorectal cancer cells.

Highlights

In the past decade, the application of radiotherapy-based preoperative neoadjuvant chemoradiotherapy has played a major role in improving surgical resection rates and rectal sphincter retention while reducing the rate of local recurrence in patients with locally advanced rectal cancer (LARC)
For patients with locally advanced rectal cancer, neoadjuvant chemoradiotherapy (nCRT) combined with total mesorectal excision (TME) is the most conventional treatment according to current guidelines and clinical practice
It is of great clinical significance to determine an efficient method or effective indicators that can be used to identify patients who are resistant to radiotherapy prior to initial treatment

Summary

Introduction

The application of radiotherapy-based preoperative neoadjuvant chemoradiotherapy (nCRT) has played a major role in improving surgical resection rates and rectal sphincter retention while reducing the rate of local recurrence in patients with locally advanced rectal cancer (LARC). Only 40-80% of patients can benefit from this treatment, and with such a large variance, no less than 20% of patients will be resistant to nCRT [1,2,3,4]. The screening out of patients with high resistance to radiotherapy before treatment will be conducive to the implementation of individualized precision therapy for LARC patients. Patient-derived xenograft (PDX) model is a xenograft model constructed by implanting newly excised tumor tissue from patients into immunodeficient mice.

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Conclusion