lncRNA miat functions as a ceRNA to upregulate sirt1 by sponging miR-22-3p in HCC cellular senescence

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.