Knockdown of circ_HIPK3 inhibits tumorigenesis of hepatocellular carcinoma via the miR-582-3p/DLX2 axis.

Hepatocellular carcinoma (HCC) is the most common type in the sub-classification of liver cancer. Circular RNAs (circRNAs) play a fundamental role in tumor occurrence and progression. This research aimed to investigate the role and molecular basis of circRNA homeodomain-interacting protein kinase 3 (circ_HIPK3) in HCC. Circ_HIPK3 and DLX2 levels were enhanced, and miR-582-3p level was reduced in HCC tissues and cells. Silencing of circ_HIPK3 impeded proliferation, migration and invasion and expedited apoptosis in HCC cells. Furthermore, circ_HIPK3 modulated HCC progression via sponging miR-582-3p, and miR-582-3p suppressed HCC progression via targeting DLX2. Moreover, circ_HIPK3 knockdown inhibited tumor growth in vivo. Circ_HIPK3 facilitated HCC progression by mediating miR-582-3p/DLX2 pathway, suggesting a new potential biomarker for HCC treatment.

Long non-coding RNA TUG1 promotes cell progression in hepatocellular carcinoma via regulating miR-216b-5p/DLX2 axis.

BACKGROUND: Accumulating evidence indicates that the long noncoding RNA taurine upregulated gene 1(TUG1) plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of TUG1 in hepatocellular carcinoma (HCC) remain largely unknown. METHODS: The expressions of TUG1, microRNA-216b-5p and distal-less homeobox 2 (DLX2) were detected by Quantitative real-time polymerase chain reaction (qRT-PCR). The target relationships were predicted by StarBase v.2.0 or TargetScan and confirmed by dual-luciferase reporter assay. The cell growth, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow cytometry and Transwell assays, respectively. All protein expression levels were detected by western blot. Tumor xenografts were implemented to explore the role of TUG1 in vivo. RESULTS: We found that there was a marked rise in TUG1 expression in HCC tissues and cells, and knockdown of TUG1 repressed the growth and metastasis and promoted apoptosis of HCC cells. In particular, TUG1 could act as a ceRNA, effectively becoming a sink for miR-216b-5p to fortify the expression of DLX2. Additionally, repression of TUG1 impared the progression of HCC cells by inhibiting DLX2 expression via sponging miR-216b-5p in vitro. More importantly, TUG1 knockdown inhibited HCC tumor growth in vivo through upregulating miR-216b-5p via inactivation of the DLX2. CONCLUSION: TUG1 interacting with miR-216b-5p contributed to proliferation, metastasis, tumorigenesis and retarded apoptosis by activation of DLX2 in HCC.

Lnc-TCL6 is a potential biomarker for early diagnosis and grade in liver-cirrhosis patients.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been applied as biomarkers in many diseases. However, scarce biomarkers are available in single lncRNA differential expression associated with different clinical stages of liver cirrhosis (LC). The aim of the study is to identify some lncRNAs that can serve as non-invasive sensitive biomarkers for early diagnosis and grade of LC. METHODS: Blood lncRNA expression was evaluated in three independent cohorts with 305 participants including healthy controls, hepatitis B virus (HBV) carriers, and patients with chronic hepatitis B (CHB) or LC. First, candidate lncRNAs were screened by CapitalBiotech microarray to diagnose cirrhosis. Quantitative reverse-transcriptase polymerase chain reaction was then used to investigate the expression of selected lncRNAs in the whole group of cirrhosis and different Child-Pugh classes. Ultimately, the diagnostic accuracy of the promising biomarker was examined and validated via Mann-Whitney test and receiver-operating characteristics analysis. RESULTS: Lnc-TCL6 was identified as a sensitive biomarker for early diagnosis of LC (Child-Pugh A) compared with healthy controls (area under the ROC curve [AUC] = 0.636), HBV carriers (AUC = 0.671), and CHB patients (AUC = 0.672). Furthermore, lnc-TCL6 showed a favourable capacity in discriminating among different Child-Pugh classes (AUC: 0.711-0.837). Compared with healthy controls, HBV carriers, and CHB patients, the expression of lnc-TCL6 was obviously up-regulated in Child-Pugh A patients and, conversely, significantly down-regulated in Child-Pugh C patients. CONCLUSIONS: Lnc-TCL6 is a novel potential biomarker for early diagnosis of LC and is a possible predictor of disease progression.

Combination Treatments of Plasma Exchange and Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation for Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure: A Clinical Trial in China.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a common type of liver failure with a high mortality. This study aimed at investigating the safety and efficacy of the combination treatment of plasma exchange (PE) and umbilical cord-derived mesenchymal stem cell (UC-MSCs) transplantation for HBV-ACLF patients. METHODS: A total of 110 HBV-ACLF patients treated in our hospital from January 2012 to September 2017 were enrolled into this trial and divided into the control group (n = 30), UC-MSC group (n = 30), PE group (n = 30), and UC-MSC + PE group (n = 20) based on their treatments. The hepatic function, coagulation, and virological and immunological markers were assessed at baseline and 30, 60, 90, 180, and 360 days. The endpoint outcomes were death and unfavorable outcome (need for liver transplantation or death). RESULTS: The UC-MSC + PE group had the lowest rates of death and unfavorable outcome at 30 days, 60 days, and 90 days posttreatment among the four groups, but the difference did not reach significances. The multivariate logistic regression analysis demonstrated that hemoglobin, prothrombin activity, and MELD (model for end-stage liver disease) score were the independent factors associated with the unfavorable outcome (all P < 0.05). The levels of total bilirubin, alanine aminotransferase, aspartate transaminase, and MELD score were significantly decreased during treatments (all P < 0.05). CONCLUSION: UC-MSCs combined with PE treatment had good safety but cannot significantly improve the short-term prognosis of HBV-ACLF patients with as compared with the single treatment. The long-term efficacy should be further evaluated. This trial is registered with registration no. NCT01724398.