Up‐regulation of microRNA‐30b/30d cluster represses hepatocyte apoptosis in mice with fulminant hepatic failure by inhibiting CEACAM1

Abstract

Recently, impacts of microRNAs have been unraveled in human diseases, and we aimed to confirm the role of miR‐30b/30d in fulminant hepatic failure (FHF). Expression of miR‐30b/30d and CEACAM1 in serum of FHF patients and healthy people was measured by reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and Western blot analysis. Mice FHF models were established by injection of D‐Galn and lipopolysaccharide, and were treated with miR‐30b/30d mimics. Oxidative stress, liver injury, and inflammatory reaction in mouse liver tissues were measured using oxidative stress‐related factor kits, hematoxylin–eosin staining and enzyme‐linked immunosorbent assay, respectively. Moreover, cell cycle distribution and apoptosis of hepatocytes of mice were determined by flow cytometry, and the target relation between miR‐30b/30d and CEACAM1 was confirmed by bioinformatic method and dual luciferase reporter gene assay. MiR‐30b/30d expression was positively, and CEACAM1 expression was negatively related to prognosis of FHF patients. Up‐regulation of miR‐30b/30d attenuated oxidative stress, liver injury, and inflammatory reaction, and improved survival rate of FHF mice. Furthermore, elevated miR‐30b/30d ameliorated apoptosis and cell cycle arrest of hepatocytes of FHF mice. CEACAM1 was a target gene of miR‐30b/30d. This study highlights that up‐regulated miR‐30b/30d attenuates the progression of FHF by targeting CEACAM1, which may be helpful to FHF treatment.

Transfer RNA‐derived fragment 5′tRF‐Gly promotes the development of hepatocellular carcinoma by direct targeting of carcinoembryonic antigen‐related cell adhesion molecule 1

“…Recent studies have shown that CEACAM1 is downregulated in HCC compared to healthy tissue specimens 24 . Its overexpression can inhibit the cell proliferation of hepatocarcinoma cells and induce hepatocyte apoptosis in fulminant hepatic failure 25,26 . The progression‐free survival of HCC was found to be related to the expression level of CEACAM1.…”

“… 24 Its overexpression can inhibit the cell proliferation of hepatocarcinoma cells and induce hepatocyte apoptosis in fulminant hepatic failure. 25 , 26 The progression‐free survival of HCC was found to be related to the expression level of CEACAM1. Low expression of CEACAM1 was significantly associated with poorer PFS of HCC based on the Kaplan–Meier plotter database (Figure 5A ).…”

A chronotherapeutics-applicable multi-target therapeutics based on AI: Example of therapeutic hypothermia

“…Referring to the previous article [ 44 ], we conservatively believed that CIRP could be identified as a negative protein from the 8H group. CEACAM1 [ 45 ] and NQO1 [ 46 ] promote apoptosis. All the other targets are shown protective effects or do not have enough data.…”

A chronopharmacology-friendly multi-target therapeutics based on AI: the example of therapeutic hypothermia

“…Referring to the previous article (67), we conservatively believed that CIRP could be identified as negative protein from 8H group. CEACAM1 (68) and NQO1(69) promote apoptosis.…”

“…Referring to the previous article [42], we conservatively believed that CIRP could be identified as a negative protein from the 8H group. CEACAM1 [43] and NQO1 [44] promote apoptosis. All the other targets are shown protective effects or don't have enough data.…”