Related Experiment Video
Updated: Aug 31, 2025
Treatment of Liver Metastases Using an Internal Target Volume Method for Stereotactic Body Radiotherapy
Published on: May 8, 2018
Regulatory network of competitively interacting RNAs and effectiveness of rectal tumors radiotherapy
Background:
Currently, rectal tumors radiotherapy effectiveness reaches an acceptable level only in a small number of patients (they have a complete clinical response), which is associated with the formation of malignant cells radioresistance. A comprehensive study that integrates various epigenetic parameters would explain a number of molecular mechanisms of rectal tumor cells radioresistance and identify new bio-markers. In the last decade, using high-through-put sequencing, the competitively interacting RNAs regulatory network (long non-coding RNAs, miRNAs and mRNAs) has been shown.
Purpose:
The aim of the study was to analyze the features of competitively interacting RNAs regulatory network functioning in patients with rectal cancer who are radioresistant and sensitive to radiotherapy. The study was performed on 500 patients with dia-gnosed rectal cancer. Radiotherapy was performed on a Novalis TX linear particle accelerator according to the standard protocol (single focal dose 2.4 Gy, total focal dose 54.0 Gy). Total RNA preparations were isolated from paired bio-psy fragments of tumor and non-tumor tissues of the rectum (obtained by video-colonoscopy). The relative abundance of mRNA, miRNA and lncRNA transcripts was assessed by the RT-qPCR method. Using bio-informatic analysis, the probability of potential interactions between the investigated mRNA, miRNA and lncRNA was determined. It has been shown that the effectiveness of radiotherapy depends on the level of miRNA (miRNA-195-5p; miRNA-4257; miRNA-5187-5p; miRNA-149-5p; miRNA-138 -1-3p; miRNA-6798-5p; miRNA-6819-5p; miRNA-4728-5p; miRNA-1249-5p; miRNA-557; miRNA-1273h-5p; miRNA-6737-5p; miRNA-6808-5p; miRNA-3202; miRNA-5195-3p; miRNA-130b-3p) and lncRNA (XIST, HELLPAR, NEAT1, AC008124. 1, LINC01089, LINC01547, and VASH1-AS1) expression, which regulate the DNA repair system (H2AX, RBBP8) and apoptosis (BCL2).
Conclusion:
A comprehensive study of competitively interacting RNAs regulatory network and radiotherapy effectiveness of rectal tumors made it possible to establish the mechanisms of radioresistance formation and its bio-markers.
Insights
This study reveals key RNA interactions influencing rectal cancer radiotherapy resistance. Identifying specific microRNAs and long non-coding RNAs offers new biomarkers for treatment effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Radiotherapy effectiveness in rectal cancer is limited by tumor radioresistance in many patients.
- Understanding the molecular mechanisms of radioresistance is crucial for improving treatment outcomes.
- Epigenetic factors, particularly RNA regulatory networks, are increasingly recognized for their role in cancer biology.
Purpose of the Study:
- To investigate the features of competitively interacting RNA networks in radioresistant versus radiosensitive rectal cancer patients.
- To identify potential RNA biomarkers associated with radiotherapy response.
- To elucidate the role of RNA interactions in the DNA repair and apoptosis pathways.
Main Methods:
- Analysis of RNA regulatory networks in 500 rectal cancer patients undergoing standard radiotherapy.
- Isolation of total RNA from paired tumor and non-tumor rectal tissues.
- Quantitative real-time PCR (RT-qPCR) to assess mRNA, miRNA, and lncRNA transcript abundance.
- Bioinformatic analysis to predict potential RNA interactions.
Main Results:
- Specific microRNAs (e.g., miRNA-195-5p, miRNA-4257) and long non-coding RNAs (e.g., XIST, NEAT1) were found to be differentially expressed in relation to radiotherapy response.
- The expression levels of these RNAs correlate with the regulation of DNA repair genes (H2AX, RBBP8) and apoptosis-related gene (BCL2).
- A distinct RNA regulatory network profile was associated with radiosensitivity or radioresistance.
Conclusions:
- A comprehensive analysis of RNA regulatory networks provides insights into the mechanisms of rectal tumor radioresistance.
- Specific microRNAs and long non-coding RNAs identified in this study serve as potential biomarkers for predicting radiotherapy effectiveness.
- Targeting these RNA interactions may offer novel therapeutic strategies for overcoming radioresistance in rectal cancer.
