Park Seong-Joon, Heo Kyu, Choi Chulwon, Yang Kwangmo, Adachi Akiko, Okada Hiroko, Yoshida Yukari, Ohno Tatsuya, Nakano Takashi, Takahashi Akihisa
Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi 371-8511, Gunma, Japan.
Dongnam Institute of Radiological & Medical Sciences, Jwadong-gil 40, Gijang-gun, Busan 619-953, Republic of Korea.
J Radiat Res. 2017 Nov 1;58(6):765-771. doi: 10.1093/jrr/rrx022.
The Lin28/let-7 axis plays an important role in tumor initiation and developmental processes. Lin28B is upregulated in a variety of cancers, and its overexpression enhances cancer cell proliferation and radioresistance through the suppression of let-7 micro RNA expression. In this study, we investigated the role of the Lin28/let7 axis as a target for radiosensitization of melanoma cancer cells. The overexpression of Lin28B reduced mature let-7 microRNA expression in melanoma cell lines, and enhanced the sphere-forming ability of melanoma cell lines, which is a characteristic of cancer stem cell (CSC) populations. Interestingly, Lin28B-overexpressed melanoma cells were more resistant to X-ray irradiation than control cells, and Lin28B-induced radioresistance was abolished after carbon ion irradiation. Consistent with these results, Lin28B overexpression reduced the numbers of γH2A.X foci after X-ray irradiation, whereas carbon ion irradiation had no such effect. Our results suggest that a carbon ion beam is more effective than an X-ray beam in terms of killing cancer cells, possibly due to elimination of CSC populations.
Lin28/let-7轴在肿瘤起始和发展过程中发挥着重要作用。Lin28B在多种癌症中上调，其过表达通过抑制let-7微小RNA的表达增强癌细胞增殖和放射抗性。在本研究中，我们探究了Lin28/let7轴作为黑色素瘤癌细胞放射增敏靶点的作用。Lin28B的过表达降低了黑色素瘤细胞系中成熟let-7微小RNA的表达，并增强了黑色素瘤细胞系的成球能力，而成球能力是癌症干细胞（CSC）群体的一个特征。有趣的是，过表达Lin28B的黑色素瘤细胞比对照细胞对X射线照射更具抗性，且碳离子照射后Lin28B诱导的放射抗性被消除。与这些结果一致，Lin28B过表达减少了X射线照射后γH2A.X焦点的数量，而碳离子照射没有这种效果。我们的结果表明，碳离子束在杀死癌细胞方面比X射线束更有效，这可能是由于消除了CSC群体。
