Long noncoding RNA Linc02023 regulates PTEN stability and suppresses tumorigenesis of colorectal cancer in a PTEN-dependent pathway.

Abstract

Phosphatase and tensin homolog (PTEN), one of the most frequently mutated tumor suppressor genes in human cancer, is pivotal in the progression of colorectal cancer. Therefore, the regulation of PTEN has emerged as a theme of intense research in tumor biology. This study aims to show that long noncoding RNA (lncRNA) Linc02023 aberrant downregulation in colorectal cancer correlates positively with the expression of PTEN and CDKN2B but negatively with the tumor size in patients and xenografted mouse models. The gain- and loss-of-function investigation reveals that Linc02023 suppresses the proliferation of colorectal cancer cells in vitro and in vivo with apoptosis promotion and cell cycle rearrangement. Mechanistically, Linc02023 specifically binds to PTEN and blocks its interaction with and ubiquitination by WWP2, stabilizing it and suppressing its downstream expression. In conclusion, this study demonstrates that lncRNA Linc02023 may serve as a novel therapeutic target by restoring the PTEN tumor suppressor activity.

• Authors: Qingyuan Wang, Yifei Feng, Wen Peng, Dongjian Ji, Zhiyuan Zhang, Wenwei Qian, Jie Li, Qiou Gu, Dongsheng Zhang, Junwei Tang, Chuan Zhang, Sen Wang, Zan Fu, Yueming Sun
• Journal: Cancer letters (Cancer Lett) Vol. 451 Pg. 68-78 (06 01 2019) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 30849479 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• RNA, Long Noncoding
• PTEN Phosphohydrolase
• PTEN protein, human

Topics

• Animals
• Carcinogenesis
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Female
• Heterografts
• Humans
• Male
• Mice
• Middle Aged
• PTEN Phosphohydrolase (metabolism)
• Protein Stability
• RNA, Long Noncoding (physiology)
• Transcriptome
• Ubiquitination