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MiR-124 and miR-506 are involved in the decline of protein C in children with extra-hepatic portal vein obstruction.

ABSTRACT: The deficiency of protein C (PROC) can be partly rescued by Rex shunt through restoring portal blood flow in children with extra-hepatic portal venous obstruction (EHPVO). However, the decline of PROC is still found in some patients with a normal portal blood flow after Rex shunt. The aim of this study was to identify the candidate miRNAs involving in the decline of PROC and their mechanism. The protein level of PROC was detected by the ELISA assay, and was compared between sick and healthy groups. The expressions of miRNAs and PROC mRNA were measured using qRT-PCR, and were compared between sick and healthy groups. The correlation between PROC and candidate miRNAs was analysed by a Pearson correlation analysis to identify the most significant miRNAs. The expression of PROC mRNA was detected by qRT-PCR in HL-7702 and LX-2 cells tansfected with miRNAs mimics or inhibitors and negative control (NC) mimics, which was compared among the different groups. The rates of liver cells' proliferation and apoptosis were detected in HL-7702 and LX-2 cells tansfected with miRNAs mimics or inhibitors or with overexpressing PROC and negative control mimics by CKK8 assay and flow cytometry, which were compared among the different groups. The expressions of COX-2 and VEGF were measured by qRT-PCR, and were compared between the miRNAs groups and NC group. Western blot was assayed for detecting the protein levels of PROC, COX-2, VEGF, Bcl-2 and Bax, which were compared between the miRNAs groups and NC group. The expression of PROC mRNA was lower, and the expressions of miR-506-3p and miR-124-3p were higher in children with EHPVO than healthy group. PROC mRNA was negatively correlated with the expression of miR-506-3p and miR-124-3p. Compared to the NC group, the transcription activity of PROC was lower after exposure of miR-506 and miR-124 mimics in HL-7702 and LX-2 cells, but this phenomenon was reversed after inhibiting miR-506 and miR-124. The rate of cell proliferation was lower after exposure of miR-506 and miR-124 than the NC group, which was increased after inhibiting miR-506 and miR-124 in HL-7702 cells and overexpressing PROC in LX-2 cells. The apoptotic rate was higher after exposure of miR-506 and miR-124 than the NC group, which was decreased after inhibiting miR-506 and miR-124 in HL-7702 cells and overexpressing PROC in LX-2 cells. The mRNA levels of COX-2 and VEGF were significantly higher after exposure of miR-506 and miR-124 mimics than those in the NC group. The protein levels of PROC and Bcl-2 were down-regulated, and the levels of COX-2, Bax and VEGF were up-regulated after exposure of miR-506 and miR-124 in HL-7702 cells, but this phenomenon was reversed after inhibiting miR-506 and miR-124. MiR-506-3p and miR-124-3p may involve in the decline of PROC in protein and transcriptional level, in which the anti-proliferation and pro-apoptosis role of miR-506-3p and miR-124-3p for liver cells may involve in this mechanism.

SUBMITTER: Zhang JS

PROVIDER: S-EPMC8192904 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background & aimsWe aimed to evaluate long-term outcome of patients with chronic non-cirrhotic extrahepatic portal vein obstruction (CNC-EHPVO) who underwent portal vein recanalisation (PVR) without transjugular intrahepatic portosystemic shunt (TIPS) insertion and to determine factors predicting PVR failure and stent occlusion.MethodsThis retrospective monocentric study included all patients who underwent PVR without TIPS insertion in the context of CNC-EHPVO between the years 2000 and 2019. Primary patency was defined by the absence of a complete stent occlusion on follow-up imaging.ResultsA total of 31 patients underwent PVR with a median follow-up of 52 months (24-82 months). Indications were gastrointestinal bleeding (n = 13), abdominal pain attributed to CNC-EHPVO (n = 7), prior to abdominal surgery (n = 4), and others (n = 7). Technical success was obtained in 27 patients. PVR failure was associated with extension within the intrahepatic portal veins (p = 0.005) and recanalisation for abdominal pain (p = 0.02). Adverse events occurred in 6 patients with no mortality. Anticoagulation was administered in 21 patients after technical success of PVR. In patients with technical success, 5-year primary patency was 73% and was associated with improved muscle mass (p = 0.007) and decreased spleen volume (p = 0.01) at 1 year. Furthermore, 21 (78%) patients with PVR technical success were free of portal hypertension complication at 5 years.ConclusionsPVR without TIPS insertion was feasible and safe in selected patients with CNC-EHPVO and portal hypertension with past or expected complications. Primary patency at 5 years was obtained in 3 of 4 patients with technical success of PVR and was associated with a control of complications of CNC-EHPVO. PVR was associated with improvement of sarcopenia and decreased spleen volume at 1 year.Lay summaryPatients with chronic obstruction of the portal vein and without cirrhosis or malignancy can develop complications related to the high pressure in the venous system. The present study reports long-term favourable outcome of patients in whom the obstruction was treated with stents.

Project description:BackgroundHepatic portal vein collateral circulation plays an important role in maintaining the perfusion of hepatic portal vein. However, at present, there is little research on collateral circulation of hepatic portal vein. Our study aims to analysis the imaging types and clinical value of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) invading and completely blocking different branches of portal vein, secondary to hepatic portal vein collateral circulation.MethodsThis study retrospectively analyzed Hepatocellular carcinoma (HCC) with PVTT diagnosed with enhanced CT examination of the upper abdomen in our hospital from May 2020 to October 2021.The inclusion criteria for patients were the following: (I) ultimately diagnosed with HCC, (II) accompanied by complete obstruction of the main portal vein or left/right branches, and (III) with collateral circulation of the hepatic portal vein established. All images were postprocessed by multiplanar reconstruction (MPR), maximum intensity projection (MIP), and other reconstruction techniques to obtain images of the abnormal portal vein system and the collateral vessels running toward the hepatic portal veins. Three physicians jointly judged the imaging anatomical classification of each collateral vessel. The qualitative variables were compared by chi-squared test.ResultsA total of 125 hepatic portal vein collateral vessels were observed in MPR and MIP reconstruction images of 71 patients with portal vein cancer thrombosis with established hepatic portal vein collateral circulation. Common hepatic collateral branches in patients with PVTT mainly include the biliary collateral branch, gastric collateral branch, mesenteric collateral branch, accessory portal vein system and the splenic branch. The incidence rate was respectively 77.5%, 36.6%, 32.4%, 28.2%, 1.41%.ConclusionsThe correct understanding of the imaging anatomical classification of the collateral vessels of the hepatic portal vein can provide clinicians with more information for diagnosis and treatment planning.

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MiR-124 and miR-506 are involved in the decline of protein C in children with extra-hepatic portal vein obstruction.

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