ABSTRACT
Being encoded by hepatitis B, hepatitis B X (HBx) protein plays crucial roles in hepatitis B-related hepatocellular carcinoma (HCC) occurrence, development, and metastasis. miRNAs also function in the progression of hepatitis B-related HCC. Hence, the objective of this study was to explore the impacts of miR-3677-3p on tumor progression and sorafenib resistance in hepatitis B-related HCC and the related underlying mechanisms. Our research revealed that miR-3677-3p and FOXM1 was up-regulated and FBXO31 was down-regulated in HBV+ HCC cells and tumor tissues from nude mice. After miR-3677-3p overexpression, cell proliferative, invasive, and migrating potentials and stemness-related protein (CD133, EpCAM, and OCT4) levels were enhanced, and cell apoptosis was reduced in Huh7 + HBx/SR cells and HepG2.2.15/SR cells. Besides, miR-3677-3p promoted the drug resistance of Huh7 + HBx/SR cells and HepG2.2.15/SR cells to sorafenib and lifted IC50. In vivo experiments, miR-3677-3p down-regulation suppressed the tumor growth in the hepatitis B HCC nude mouse models. Mechanistically, miR-3677-3p targeted and negatively-regulated FBXO31 and FBXO31 could enrich FOXM1 protein. miR-3677-3p down-regulation or FBXO31 overexpression promoted the ubiquitylation of FOXM1. In a word, miR-3677-3p bound to FBXO31 and inhibited FBXO31 expression, thus curtailing the ubiquitylation degradation of FOXM1, contributing to HCC development and sorafenib resistance.
Subject(s)
Carcinoma, Hepatocellular , Forkhead Box Protein M1 , Liver Neoplasms , MicroRNAs , Animals , Mice , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic/genetics , Hepatitis B/genetics , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Mice, Nude , MicroRNAs/genetics , MicroRNAs/metabolism , Sorafenib/pharmacology , Forkhead Box Protein M1/genetics , Forkhead Box Protein M1/metabolism , HumansABSTRACT
Laparoscopic Nissen fundoplication and esophagoplasty are the standards for gastroesophageal reflux disease (GERD) and hiatal hernia (HH) repair. Biologically derived mesh is also associated with reduced recurrence. This study attempted to evaluate the effectiveness of a biological mesh in the 4K laparoscopic repair of HH. This retrospective study reviewed patients with a severe GERD complicated with HH from August 2019 to August 2020. All patients underwent the HH repair using a biological mesh under a 4K laparoscope accompanying Nissen fundoplication. Up to 16 months postoperatively, GERD-health-related quality-of-life (GERD-HRQL) scale, radiologic studies on HH recurrence, and symptoms were recorded. The mean surgical time and postoperative hospital stay were 70.9â ±â 8.72 min, 4.8â ±â 0.76 days, respectively. The postoperative symptom relief rate was 96.5%, and no recurrence exhibited during follow-up. Dysphagia occurred in 10 (9.43%) patients. There were no intraoperative vagus nerve injury or postoperative complications, mesh infection, and reoperation for mesh. The tension-free repair of HH with the biological mesh is an option for clinical use, with effectiveness and few short-term complications being reported.
Subject(s)
Gastroesophageal Reflux , Hernia, Hiatal , Humans , Hernia, Hiatal/surgery , Herniorrhaphy/adverse effects , Surgical Mesh/adverse effects , Retrospective Studies , Gastroesophageal Reflux/complicationsABSTRACT
Long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) has been found to be highly expressed in gastric cancer (GC). However, the study for exploring the effects of SNHG1 and microRNA (miR)-195-5p on GC is limited. This research commits to unravel the regulatory effects of SNHG1, miRNA-195-5p, and Yes-associated protein 1 (YAP1) on GC. SNHG1, miR-195-5p and YAP1 levels in GC tissues and GC cells were detected. The GC cells were treated with various constructs altering SNHG1 or miR-195-5p expression to determine the biological activities of GC cell in vitro. The effect of SNHG1 inhibition on subcutaneous tumorigenesis of GC cells in a nude mouse model in vivo was detected. The binding relation among SNHG1, miR-195-5p, and YAP1 was validated. SNHG1 and YAP1 levels were elevated and miR-195-5p level was reduced in GC. Reduction of SNHG1 or elevation of miR-195-5p retarded GC cell biological activity in vitro. Downregulated SNHG1 suppressed tumor growth in vivo. SNHG1 bound to miR-195-5p, and miR-195-5p directly targeted YAP1. The downregulated SNHG1 hinders the biological behaviors of GC cells via the modulation of the miR-195-5p/YAP1 axis.
