期刊
CANCER LETTERS
卷 381, 期 1, 页码 41-48出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.07.024
关键词
Melanoma; Therapeutic efficacy; ANRIL; INK4A; INK4B
类别
资金
- Scientific Research Program of the National Health and Family Planning Commission of China [201402014]
- National Natural Science Foundation of China [31470757, U1432117, 81372469]
- Program for Professor of Special Appointment (Eastern Scholar) at the Shanghai Institutions of Higher Learning [1410000159]
- SMC-ChenXing Yong Scholar Program (Class B)
- Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant [2016-13]
- Science and Technology Commission of Shanghai [14JC1404100, 14JC1404200, 14430723100]
Melanoma is an extremely aggressive disease with rapid progression, high metastatic potential and recurrence. Simultaneous correction of multiple tumor-specific gene abnormalities has become an attractive approach for developing therapeutics to treat melanoma. To potentiate anti-melanoma activity, we tested a domino effect-like therapeutic approach by uniquely targeting one defect and automatically triggering the endogenous corrections of other defects. Using this strategy, in a suspicious INK4b-ARF-INK4a gene cluster at chromosome 9p21, aberrant INK4a and INIC4b defects were simultaneously endogenously auto-corrected after targeting the suppression of abnormal ANRIL lncRNA. In cell culture, this treatment significantly reduced the tumor metastatic capacity and tumor formation compared with absence of treatment. In animals harboring tumor xenografts, this therapeutic approach significantly inhibited tumor growth and reduced the tumor weight. Our results reveal a novel therapeutic strategy that significantly potentiates anti-melanoma efficiency by reprogramming the aberrant INK4-hub. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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