Long noncoding RNA DANCR promotes colorectal cancer proliferation and metastasis via miR-577 sponging

• Published in: Experimental & molecular medicine 2018, 50(0), , pp.1-17
• Main Authors: Wang, Yong, Lu, Zhi, Wang, Ningnin, Feng, Jianzhou, Zhang, Junjie, Luan, Lan, Zhao, Wei, Zeng, Xiandong
• Format: Article
• Language: English
• Subjects: 42/41; 631/337/384/2568; 631/67/395; Animals; Base Sequence; Binding sites; Biomedical and Life Sciences; Biomedicine; Cell Line, Tumor; Cell Proliferation - genetics; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Female; Gene Expression Regulation, Neoplastic; Heat shock proteins; HSP27 Heat-Shock Proteins - metabolism; Hsp27 protein; Humans; Liver; Male; Medical Biochemistry; Metastases; Metastasis; Mice, Inbred NOD; Mice, SCID; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Models, Biological; Molecular Chaperones; Molecular Medicine; Neoplasm Metastasis; Non-coding RNA; Prognosis; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Stem Cells; Tumors; Up-Regulation - genetics; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-018-0082-5

Long non-coding RNAs (lncRNAs) play key roles in various malignant tumors, including colorectal cancer (CRC). Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) is overexpressed in CRC patients, but whether it affects CRC proliferation and metastasis via regulation of heat shock protein 27 (HSP27) remains unclear. In the present study, we found that DANCR was highly expressed and correlated with proliferation and metastasis in CRC. In addition, we demonstrated that DANCR and HSP27 were both targets of microRNA-577 (miR-577) and shared the same binding site. Furthermore, we revealed that DANCR promoted HSP27 expression and its mediation of proliferation/metastasis via miR-577 sponging. Finally, using an in vivo study, we confirmed that overexpression of DANCR promoted CRC tumor growth and liver metastasis. The present study demonstrated the function of DANCR in CRC and might provide a new target in the treatment of CRC. Colorectal cancer: Long non-coding RNA offers new drug target A long non-coding RNA linked to colorectal cancer causes tumor progression by unleashing the activity of a protein involved in cell proliferation and spread. Researchers in China led by Xiandong Zeng from Shenyang Medical College explain why the expression of a long non-coding RNA molecule known as DANCR correlates with poor prognosis in patients and mouse models carrying colorectal cancer tissue. They showed that DANCR displaces a small regulatory microRNA from its normal binding spot on the gene transcript that encodes HSP27, a protein involved in the growth and metastasis of colorectal cancer cells. This microRNA normally suppresses HSP27 activity, whereas DANCR, by outcompeting the microRNA, promotes HSP27 expression, leading to cell proliferation and metastasis. Drugs that block DANCR could thus help treat the disease.