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Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
Published on: August 21, 2019
Therapeutic Delivery of miR-29b Enhances Radiosensitivity in Cervical Cancer
Tingting Zhang1, Xiang Xue1, Huixia Peng2
1Department of Gynecology, The Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China; Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, China.
Abstract:
Radioresistant cervical cancer is likely to give rise to local recurrence, distant metastatic relapse, and decreased survival rates. Recent studies revealed microRNA mediated regulation of tumor aggressiveness and metastasis; however, whether specific microRNAs regulate tumor radioresistance and can be exploited as radiosensitizing agents remains unclear. Here, we find that miR-29b could promote radiosensitivity in radioresistant subpopulations of cervical cancer cells. Notably, therapeutic delivery of miR-29b mimics via R11-SSPEI nanoparticle, whose specificity has been proved by our previous studies, can sensitize the tumor to radiation in a xenograft model. Mechanistically, we reveal a novel function of miR-29b in regulating intracellular reactive oxygen species signaling and explore a potential application for its use in combination with therapies known to increase oxidative stress such as radiation. Moreover, miR-29b inhibits DNA damage repair by targeting phosphate and tension homology deleted on chromsome ten (PTEN), and overexpression of PTEN could partially rescue miR-29b-mediated homologous recombination (HR)-DNA damage repair and increase radiosensitivity. These findings identify miR-29b as a radiosensitizing microRNA and reveal a new therapeutic strategy for radioresistant tumors.
Insights
MicroRNA-29b (miR-29b) enhances radiosensitivity in cervical cancer by regulating reactive oxygen species and DNA repair. This discovery offers a new therapeutic strategy for radioresistant tumors.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Radioresistant cervical cancer leads to poor outcomes, including recurrence and metastasis.
- MicroRNAs (miRNAs) are implicated in tumor aggressiveness, but their role in radioresistance is not fully understood.
Purpose of the Study:
- To investigate the role of specific microRNAs in regulating cervical cancer radioresistance.
- To explore the potential of microRNAs as radiosensitizing agents.
Main Methods:
- Investigated miR-29b's effect on radioresistant cervical cancer cell lines.
- Utilized R11-SSPEI nanoparticles for therapeutic delivery of miR-29b mimics in a xenograft model.
- Examined miR-29b's mechanism involving reactive oxygen species (ROS) signaling and DNA damage repair pathways, including targeting PTEN and homologous recombination (HR).
Main Results:
- miR-29b promotes radiosensitivity in radioresistant cervical cancer cells.
- Therapeutic delivery of miR-29b mimics via nanoparticles sensitizes tumors to radiation in vivo.
- miR-29b regulates intracellular ROS and inhibits DNA damage repair by targeting PTEN, affecting HR-DNA repair.
- PTEN overexpression partially rescues miR-29b-mediated effects and increases radiosensitivity.
Conclusions:
- miR-29b acts as a radiosensitizing microRNA in cervical cancer.
- miR-29b's novel mechanism involves regulating ROS and inhibiting DNA repair via PTEN.
- miR-29b represents a promising therapeutic strategy for overcoming radioresistance in cervical cancer.
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