miR-544a Stimulates endometrial carcinoma growth via targeted inhibition of reversion-inducing cysteine-rich protein with Kazal motifs.

Endometrial carcinoma (EC) is a female-specific malignant tumor. Although current treatments can achieve good outcomes and improve patient survival, there remains a high incidence of treatment-induced infertility, a serious side effect that is unacceptable to those of childbearing age. Studies have demonstrated that micro ribonucleic acids (microRNAs or miRNAs) such as miR-544a regulate tumor-related gene expression. However, whether miR-544a is involved in the progression of EC is unknown. This study aimed to investigate the biological functions and underlying mechanisms of miR-544a in EC in vivo and in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed miR-544a overexpression in EC tissue and cell lines, which was associated with a decreased in overall survival as revealed by Kaplan-Meier analysis. Functionally, the miR-544a inhibitor restricted the proliferation [detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay], invasion, and migration (detected by transwell assay) of human endometrial adenocarcinoma cells (HEC-1B and Ishikawa) and facilitated cell apoptosis (detected by flow cytometry assay). Western blotting analysis revealed that the miR-544a inhibitor decreased the expressions of matrix metalloproteinase (MMP)-2 and MMP-9 and elevated the levels of cleaved caspase3 and cleaved poly (ADP-ribose) polymerase. Furthermore, animal experiments indicated that the miR-544a antagonist (antagomir-544a) suppressed tumor growth significantly in a mouse xenograft model. The mechanistic, qRT-PCR, and immunohistochemical indications were that a reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and miR-544a had inverse expression changes in EC. Bioinformatics analysis revealed RECK as a potential target for miR-544a, and this was verified by the dual-luciferase reporter assay. Subsequently, in vitro experiments, including transwell assay, MTT assay, flow cytometry assay, and Western blotting analysis, demonstrated that RECK exerted antitumor effects on EC, which were negatively regulated by miR-544a. Taken together, our study findings suggested miR-544a as a valuable target in EC therapy.

Diagnostic and prognostic significance of serum miR-24-3p in HBV-related hepatocellular carcinoma.

The aim of this study was to explore the diagnostic and prognostic value of serum microRNAs (miRNAs) in hepatitis B viral (HBV)-related hepatocellular carcinoma (HCC). We retrospectively analyzed clinical data of 84 consecutive patients with HBV-related HCC who underwent curative resection. Additionally, we enrolled 46 healthy controls and 31 patients with chronic liver disease (CLD). Serum levels of miR-155-5p, miR-24-3p, miR-490-3p, miR-210-3p, and miR-335-5p were measured. Associations of serum miRNAs with clinicopathological factors were evaluated. Receiver operating characteristic curves were established for discriminating HCC patients from CLD patients, and the area under the curve (AUC) was calculated. Overall survival (OS) and disease-free survival (DFS) were examined by the Kaplan-Meier method. Prognostic factors were determined by multivariate Cox analysis. Consequently, serum miR-24-3p levels were significantly greater in HCC patients than healthy controls and CLD patients. Serum miR-24-3p was significantly associated with vascular invasion in HCC patients. Serum miR-24-3p discriminated HCC patients from CLD, with an AUC of 0.636 [95 % confidence interval (CI) 0.524-0.748]. Combined serum alpha-fetoprotein (AFP) and miR-24-3p had an increased AUC of 0.834 (95 % CI 0.745-0.923; P < 0.001). Elevated serum miR-24-3p was an independent poor prognostic factor for OS and DFS of HCC patients. In conclusion, the combination of serum miR-24-3p and AFP improves the diagnostic accuracy for HCC prediction compared to each biomarker alone. High serum miR-24-3p level is an independent predictor of poor OS and DFS in patients with HBV-related HCC.

Protective effect of S-adenosylmethionine on hepatic ischemia-reperfusion injury during hepatectomy in HCC patients with chronic HBV infection.

BACKGROUND: Although hepatectomy is often performed with the Pringle maneuver, the problem of hepatic ischemia-reperfusion injury (HIRI) can also be serious. Thus, the present study was designed to investigate the protective effect of S-adenosylmethionine (SAMe) on HIRI, especially for patients with hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus (HBV) infection and cirrhosis. METHODS: Eighty-one HCC patients with chronic HBV infection, undergoing partial hepatectomy with inflow occlusion, were divided into three groups. In the pretreatment group (PR group, n = 26), patients were given SAMe two hours before surgery. In the post-treatment group (PO group, n = 25), patients were given SAMe six hours after surgery. And in the control group (control group, n = 30), patients received partial hepatectomy without any SAMe. All pre-, intra- and postoperative blood samples were collected to measure the plasma levels of transaminases, bilirubin and cytokines. The results were compared among the three groups. RESULTS: There were no statistically significant intergroup differences observed in age, gender, hepatic inflow occlusion time and the results of liver function tests. Preoperative administration of SAMe (PR group) significantly reduced the plasma levels of alanine transaminase (ALT), aspartate transferase (AST), total bilirubin (TBIL) and direct bilirubin (DBIL) as compared to the other two groups. In the PO group, TBIL and DBIL were significantly lower than in the control group. Significant differences were also seen in IL-6 and TNF-α between the PR group and the other groups. In all groups, postoperative liver reserve function in the PR group as revealed by ICGR15 (Post ICGR15) was at its best before abdominal closure. Compared to the control group, the risk of complications and the hospital stay after surgery were significantly meliorated in the PR group. Additionally, patients with cirrhosis had a more acute rate of change in ALT and AST than non-cirrhotic patients. CONCLUSIONS: Taken together, our preliminary findings suggest that preoperative administration of SAMe is useful and safe for reducing the HIRI in partial hepatectomy, especially for HCC patients whose disease is associated with chronic HBV infection and cirrhosis.