MiR-22 as a metabolic silencer and liver tumor suppressor

Abstract

With obesity rate consistently increasing, a strong relationship between obesity and fatty liver disease has been discovered. More than 90% of bariatric surgery patients also have non-alcoholic fatty liver diseases (NAFLDs). NAFLD and non-alcoholic steatohepatitis (NASH), which are the hepatic manifestations of metabolic syndrome, can lead to liver carcinogenesis. Unfortunately, there is no effective medicine that can be used to treat NASH or liver cancer. Thus, it is critically important to understand the mechanism underlying the development of these diseases. Extensive evidence suggests that microRNA 22 (miR-22) can be a diagnostic marker for liver diseases as well as a treatment target. This review paper focuses on the roles of miR-22 in metabolism, steatosis, and liver carcinogenesis. Literature search is limited based on the publications included in the PubMed database in the recent 10 years.

Keywords: Cancer; Hepatitis; Liver; Metabolism; MicroRNA-22(miR-22); Non-alcoholic steatohepatitis; Steatosis.

Fig. 1.. MiR-22 expression level in different cancers.

The miR-22 expression level (log₂) was analyzed using TCGA Data Portal and data are shown as box plot (white box, normal specimens; gravy box: cancer specimens).

Fig. 2.. The associations between miR-22 levels and HCC clinical features.

The correlation between miR-22 expression level (log₂) and (A) the depth of tumor invasion and (B) tumor stages. Kaplan-Meier curves showed the relationships between miR-22 levels and (C) overall survival and (D) disease-free survival. P-values were calculated by the log-rank test. Clinical features and P values are summarized in (E).

Fig. 3.. The regulation and function of miR-22.

MiR-22 can be induced by ligands for nuclear receptors such as retinoic acid, bile acids, as well as chemicals that have HDAC inhibitory property. Transcription factor Nrf1α and Nuf2α also induce miR-22. All those chemicals and transcriptional factors have known anti-cancer effects. Abbreviations: miR-22,microRNA 22; HDAC, histone deacetylase; Nrf1α, nuclear respiratory factor 1; Nrf2α, NF-E2-related factor 2a; RARβ, retinoic acid receptor beta; FXR, farnesoid X receptor; HNRNPA1, heterogeneous nuclear ribonucleoprotein A1; ZEB2, Zinc finger E-box binding homeobox 2; OCT4, octamer-binding transcription factor 4; NUR77, nuclear receptor subfamily 4 group A member 1; SIRT1, sirtuin 1; PTEN, phosphatase and tensin homolog; CCNA2, cyclin A2; NCOA1, nuclear receptor coactivator 1; NF-κB, nuclear factor kappa B; MTA3, metastasis associated 1 family member 3.