KIRAMS / 김은숙, 배인화*
Abstract
Although radiotherapy has been successfully applied to treat many cancer types, surviving cancer cells often acquire therapeutic resistance, leading to increased risk of local recurrence and distant metastases via modification of the tumor microenvironment. Previously, we reported that high expression of Bcl-w in cancer patients is significantly correlated with poor survival as well as malignant activity. However, the relationship between ionizing radiation (IR)-induced resistance and Bcl-w expression in cancer cells is currently unclear. We showed that IR-induced Bcl-w contributes to EMT (epithelial-mesenchymal transition), migration, angiogenesis, stemness maintenance, and metastasis by promoting the expression of factors related to these phenotypes, both in vitro and in vivo. Meanwhile, IR enhanced hypermethylation of miR-205-5p CpG islands through Src activation, leading to decreased miR-205-5p expression and, in turn, potentially stimulating Bcl-w-mediated malignant activity and metastasis. The clinical applicability of Bcl-w and miR-205-5p from cells or animal models was confirmed using tissues and plasma of breast carcinoma patients. Based on the collective findings, we propose that miR-205-5ps as important negative mediators of resistance in radiotherapy could serve as useful potential targets of concurrently applied genetic therapy aimed to inhibit tumor aggressiveness and enhance the efficiency of radiotherapy in cancer patients.
Author information
Kim ES1, Choi JY1, Hwang SJ1, Bae IH2.
1
Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea.
2
Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea. Electronic address: ihbae@kirams.re.kr
편집위원
방사선에 의해 암발생 및 억제, 전이 관련하여 microRNA가 관여할것이라는 추정은 되었으나, 그 중 주요 microRNA를 발굴했고, 이에 의해 암발생 및 전이에 direct하게 관여함을 증명한 논문이라고 사료됨
2019-04-17 16:08:18
김진수
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2019-04-25 19:28:44