MiR-124 Radiosensitizes human colorectal cancer cells by targeting PRRX1
Yuqin Zhang1, Lin Zheng2, Jing Huang3
1Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Abstract:
One of the challenges in the treatment of colorectal cancer patients is that these tumors show resistance to radiation. MicroRNAs (miRNAs) are involved in essential biological activities, including chemoresistance and radioresistance. Several research studies have indicated that miRNA played an important role in sensitizing cellular response to ionizing radiation (IR). In this study, we found that miR-124 was significantly down-regulated both in CRC-derived cell lines and clinical CRC samples compared with adjacent non-tumor colorectal tissues, MiR-124 could sensitize human colorectal cancer cells to IR in vitro and in vivo. We identified PRRX1, a new EMT inducer and stemness regulator as a novel direct target of miR-124 by using target prediction algorithms and luciferase assay. PRRX1 knockdown could sensitize CRC cells to IR similar to the effects caused by miR-124. Overexpression of PRRX1 in stably overexpressed-miR-124 cell lines could rescue the effects of radiosensitivity enhancement brought by miR-124. Taking these observations into consideration, we illustrated that miR-124 could increase the radiosensitivity of CRC cells by blocking the expression of PRRX1, which indicated miR-124 could act as a great therapeutic target for CRC patients.
Insights
MicroRNA-124 (miR-124) is down-regulated in colorectal cancer (CRC), contributing to radioresistance. Restoring miR-124 sensitizes CRC cells to ionizing radiation (IR) by targeting PRRX1.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancer (CRC) often exhibits resistance to radiation therapy.
- MicroRNAs (miRNAs) regulate cellular processes, including chemoresistance and radioresistance.
- miRNA dysregulation is implicated in cancer progression and treatment resistance.
Purpose of the Study:
- To investigate the role of miR-124 in colorectal cancer radiosensitivity.
- To identify the molecular targets of miR-124 involved in radioresistance.
- To explore miR-124 as a potential therapeutic target for enhancing CRC radiation treatment.
Main Methods:
- Quantitative real-time PCR to measure miR-124 levels in CRC cell lines and tissues.
- In vitro and in vivo assays to assess the effect of miR-124 on CRC cell radiosensitivity.
- Bioinformatic target prediction and luciferase reporter assays to identify miR-124 targets.
- Western blotting and knockdown/overexpression studies to validate PRRX1 as a miR-124 target.
Main Results:
- miR-124 was significantly downregulated in CRC cells and clinical samples.
- Overexpression of miR-124 sensitized CRC cells to ionizing radiation (IR) in vitro and in vivo.
- PRRX1 was identified as a direct target of miR-124, acting as an EMT inducer and stemness regulator.
- PRRX1 knockdown mimicked the radiosensitizing effects of miR-124, and PRRX1 overexpression rescued these effects.
Conclusions:
- miR-124 enhances colorectal cancer cell radiosensitivity by directly targeting and downregulating PRRX1 expression.
- The miR-124/PRRX1 axis represents a novel mechanism contributing to CRC radioresistance.
- miR-124 holds potential as a therapeutic agent to improve radiation therapy outcomes for CRC patients.
