Format

Send to

Choose Destination
Cancer Lett. 2016 Oct 10;381(1):41-8. doi: 10.1016/j.canlet.2016.07.024. Epub 2016 Jul 25.

ANRIL lncRNA triggers efficient therapeutic efficacy by reprogramming the aberrant INK4-hub in melanoma.

Author information

1
Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
2
Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. Electronic address: zhanghe@sjtu.edu.cn.
3
Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. Electronic address: drfanxianqun@126.com.

Abstract

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 INK4b 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.

KEYWORDS:

ANRIL; INK4A; INK4B; Melanoma; Therapeutic efficacy

PMID:
27461581
DOI:
10.1016/j.canlet.2016.07.024
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center