Research Paper Volume 11, Issue 17 pp 7098—7122
lncRNA miat functions as a ceRNA to upregulate sirt1 by sponging miR-22-3p in HCC cellular senescence
- 1 Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing 100191, China
- 2 Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100191, China
- 3 Department of Laboratory Medicine, Peking University Third Hospital, Beijing 100191, China
- 4 Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China
- 5 Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China
- 6 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
received: April 22, 2019 ; accepted: August 22, 2019 ; published: September 10, 2019 ;https://doi.org/10.18632/aging.102240
How to Cite
Copyright © 2019 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Hepatocellular carcinoma (HCC) is a leading cause of cancer related deaths and lacks effective therapies. Cellular senescence acts as a barrier against cancer progression and plays an important role in tumor suppression. Senescence associated long noncoding RNAs (SAL-RNAs) are thought to be critical regulators of cancer development. Here, the long noncoding RNA (lncRNA) myocardial infarction-associated transcript (miat) was first identified as an HCC specific SALncRNA. Knockdown of miat significantly promoted cellular senescence and inhibited HCC progression. Mechanistic study revealed that SAL-miat acted as a competitive endogenous RNA (ceRNA) that upregulated the expression of sirt1 by sponging miR-22-3p. Moreover, miat downregulation activated the tumor suppressor pathway (p53/p21 and p16/pRb) and stimulated senescent cancer cells to secrete senescence-associated secretory phenotype (SASP), which contributed to inhibition of tumor cell proliferation, and resulted in the suppression of HCC tumorigenesis. Together, our study provided mechanistic insights into a critical role of miat as a miRNA sponge in HCC cellular senescence, which might offer a potential therapeutic strategy for HCC treatment.