Carbon ion irradiation abrogates Lin28B-induced X-ray resistance in melanoma cells

Area of Science:

• Oncology
• Molecular Biology
• Radiation Biology

Background:

• The Lin28/let-7 axis is crucial in tumor initiation and development.
• Lin28B overexpression promotes cancer cell proliferation and radioresistance by suppressing let-7 microRNA.
• Cancer stem cells (CSCs) contribute to tumor progression and treatment resistance.

Purpose of the Study:

• To investigate the Lin28/let-7 axis as a radiosensitization target in melanoma.
• To compare the efficacy of X-ray and carbon ion irradiation in Lin28B-overexpressing melanoma cells.
• To assess the impact on cancer stem cell populations.

Main Methods:

• Melanoma cell lines were engineered to overexpress Lin28B.
• Cells were subjected to X-ray and carbon ion irradiation.
• let-7 microRNA levels, sphere-forming ability (CSC marker), and DNA damage (γH2A.X foci) were analyzed.

Main Results:

• Lin28B overexpression reduced let-7 levels and increased CSC-like properties in melanoma cells.
• Lin28B-overexpressing cells showed radioresistance to X-rays but not to carbon ions.
• Carbon ion irradiation did not increase γH2A.X foci in Lin28B-overexpressing cells, unlike X-rays.

Conclusions:

• Carbon ion irradiation may be more effective than X-ray irradiation for killing melanoma cells, potentially by eliminating CSC populations.
• The Lin28/let-7 axis plays a role in radioresistance, particularly against X-ray therapy.
• Targeting the Lin28/let-7 axis in conjunction with carbon ion therapy could be a promising strategy for melanoma treatment.