HBX suppresses PTEN to promote the malignant progression of hepatocellular carcinoma through mi-R155 activation.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most common and fatal tumors in the world, ranking third in cancer-related mortality. Chronic HBV infection is one of the major risk factors for hepatocellular carcinoma in China, Korea, and Sub-Saharan Africa. The HBx protein encoded by the X gene of HBV is a broadly regulated protein involved in transcriptional activation, epigenetics, apoptosis, DNA repair, and other regulatory processes. This study aimed to investigate the mechanism of HBx regulation of miR-155 and PTEN (Phosphatase and tensin homolog deleted on chromosome ten) in HBV-HCC. METHODS: Exosomal miR-155 quantity was analyzed by sampling serum exosomes of patients with hepatocellular carcinoma and normal subjects. The analysis was divided into different subgroups according to HBV positivity or negativity. At the cellular level, the biological roles of HBX, microRNA-155 and PTEN on hepatocellular carcinoma cells and their regulatory relationships with each other were verified. RESULTS: MicroRNA-155 and PTEN expression in HBV-positive HCC liver cancer tissues were negatively correlated, and HBX and miR-155 expression were positively correlated; microRNA-155 could target and inhibit PTEN expression, thereby promoting hepatocellular carcinoma cell activity, inhibiting apoptosis, and promoting invasion and migration; HBX could upregulate microRNA-155 thereby inhibit PTEN to promote malignant transformation of hepatocellular carcinoma. CONCLUSIONS: HBX could promote malignant transformation of hepatocellular carcinoma cells by upregulating microRNA-155 expression and thereby inhibiting the PTEN/PI3K-AKT pathway. Blocking miR-155 expression could attenuate the proliferation-promoting and invasive effects of HBX.

Exosomal microRNA-155 as a biomarker for hepatic fibrosis diagnosis and progression.

BACKGROUND: Pathological examination of liver biopsies remains the gold standard for evaluating the stage of hepatic fibrosis, which are a number of disadvantages associated with biopsy. The aim of the present study was to investigate the potential of exosomal microRNA (miR)-155 as a non-invasive biomarker for the diagnosis and progression of hepatic fibrosis. METHODS: Exosomal miR-155 quantity was analyzed by sampling serum exosomes of patients with hepatic fibrosis and a hepatic fibrosis rat model. A total of 94 patients were divided into three groups based on Child-Pugh rating. Additionally, 30 patients with primary liver fibrosis who underwent liver transplantation were divided into the low miR-155 expression group and the high expression group; 56 rats were divided into 7 groups (n=8, 0, 2, 4, 6, 8, 10, and 12 weeks). Rats in every group were intravenously injected with CCl4 (3% vol/vol in olive oil; 0.3 mL/100 g body weight) twice weekly to produce different degrees of liver necrosis and liver fibrosis. RESULTS: Exosomal miR-155 was found to be closely associated with the progression of cirrhosis and clinical prognostic indicators of cirrhosis. Exosomal miR-155 gradually increased with the severity of hepatic necrosis and fibrosis. CONCLUSIONS: The findings of the present study indicate that exosomal miR-155 can act as a non-invasive biomarker for the diagnosis and progression of hepatic fibrosis.

Comparison between surgery plus radiotherapy and radiotherapy alone in treating breast cancer patients with ipsilateral supraclavicular lymph node metastasis.

BACKGROUND: Ipsilateral supraclavicular lymph node metastasis (ISLM) with breast cancer patients has always been a hard problem for breast surgery. It is generally believed that radiotherapy can benefit the survival of patients, but whether local surgical resection is needed or not is controversial. The study aims to compare the efficacy between supraclavicular lymph node (SLN) dissection combined with radiotherapy and radiotherapy alone in the treatment of breast cancer with ISLM. METHODS: A retrospective analysis was performed using 122 cases of breast cancer with ISLM but without distant metastasis. Among them, 14 cases were eliminated due to insufficient data. The 108 remaining cases were divided into 2 groups based on different treatment proposals for metastatic SLNs. The groups were dissection plus radiotherapy (surgery group), and simple radiotherapy (radiotherapy group). RESULTS: For the 108 patients, the overall 5-year disease-free survival (DFS) and overall survival (OS) rates were 30.6% and 67.8%, respectively. In the surgery group, distant metastases occurred in 41 patients, and the 5-year DFS was 34.3%; in the radiotherapy group, 18 patients had distant metastases, and the 5-year DFS was 26.1%; the difference was not statistically significant (P>0.05). In the surgery group, 11 patients died, and the 5-year OS rate was 67.9%; in the radiotherapy group, 6 patients died, and the 5-year OS rate was 67.5%; the difference was not statistically significant (P>0.05). CONCLUSIONS: The dissection of SLN combined with radiotherapy and radiotherapy alone had similar effects on the survival rates in breast cancer patients with ISLM. The local control in the surgery group was better than that in the radiotherapy group. The status of estrogen receptors (ER) and the number of axillary lymph node metastases were independent influencing factors of DFS. The ER status is an independent factor affecting the OS rate of patients.