No abstract

These results show that in addition to changes in the signaling pathways, such as the Ras-Raf-MEK-ERK pathway, altered mitochondrial DNA replication and protein folding in liver cancer are also worth studying further. Collectively, these results suggest that specific mitochondrial proteins are uniquely susceptible to alterations in expression and carry implications for the investigation of their potential as therapeutic and prognostic markers. Further studies focusing on these proteins will be used to predict treatment response and reverse the apoptosis resistance.

Background: Circular RNAs have been emerging as biomarkers in diagnosis and prognosis of pancreatic ductal adenocarcinoma (PDAC). The hsa_circ_0013912 (circ_0013912) has been retrieved to be upregulated in PDAC. Here, we further investigated its role in PDAC cells, as well as its mechanism via serving as competing endogenous RNA (ceRNA) for miRNA (miR)-7-5p, which is abundant in pancreas and suppresses the development of PDAC. Materials and Methods: The clinical human tissues were harvested from Gene Expression Omnibus (GEO) database and PDAC patients, and expression of circ_0013912 and miR-7-5p was detected by real-time quantitative PCR. The interaction between both was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation and biotin-miRNA pull-down assay. Functional experiments were performed using Cell Counting Kit-8 assay, colony formation assay, fluorescence-activated cell separation method, caspase 3 activity assay kit, Western blotting, transwell assays, and xenograft tumor model. Results: circ_0013912 was upregulated in PDAC tumors and cells; besides, circ_0013912 upregulation was associated with TNM stage and lymph node metastasis. Silencing circ_0013912 inhibited cell viability, colony formation ability, cell cycle entrance, migration and invasion, but facilitated apoptosis rate and caspase 3 activity in PANC-1 and AsPC-1 cells, accompanied with decreased c-myc, cyclin D1 and vimentin, and increased E-cadherin. Furthermore, miR-7-5p was a target of circ_0013912. Blocking miR-7-5p could promote cell growth, migration and invasion of PANC-1 and AsPC-1 cells with circ_0013912 silencing or not. Tumor growth was also restrained by circ_0013912 downregulation. Conclusion: Circ_0013912 knockdown could suppress cell growth and metastasis of PDAC cells via sponging miR-7-5p.

Background: Hepatocellular carcinoma (HCC) is the leading threat of cancer-related death in humans. Increasing studies show that circular RNAs (circRNAs) are important indicators in cancer diagnosis and prognosis. This study intended to explore the function and mechanism of circ_0015756 in HCC, providing the additional opinion for HCC treatment. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of circ_0015756 and miR-610. Cell viability was assessed by cell counting kit-8 (CCK-8) assay, and colony formation capacity was ascertained by colony formation assay. Cell migration and invasion were monitored by transwell assay. Cell cycle progression and apoptosis were analyzed by flow cytometry assay. Circ_0015756 oncogenicity was determined by Xenograft models. The targets of circ_0015756 and miR-610 were predicted by bioinformatics tools and validated using RNA pull-down, RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. The expression level of fibroblast growth factor receptor 1 (FGFR1) was measured by Western blot. Results: The expression of circ_0015756 was increased in HCC tissues, serums and cells. Circ_0015756 downregulation impaired HCC cell viability, colony formation capacity, invasion and migration, induced cell cycle arrest and apoptosis, and inhibited tumor growth in vivo. MiR-610 was ensured as a target of circ_0015756, and miR-610 absence reversed the effects of circ_0015756 downregulation. Further, FGFR1 was targeted by miR-610, and FGFR1 overexpression overturned the effects of miR-610 restoration in HCC cells. Circ_0015756 could regulate FGFR1 expression by targeting miR-610. Conclusion: Circ_0015756 played its tumorigenic properties in HCC by activating FGFR1 via sponging miR-610, and circ_0015756 was expected to be a vital indicator in HCC diagnosis and treatment.

Resection has been commonly utilized for treating huge hepatocellular carcinoma (HCC) with a diameter of ≥10 cm; however, a high rate of mortality is reported due to recurrence. The present study was designed to predict the recurrence following resection based on preoperative and postoperative machine learning models. In total, 1,082 patients with HCC who underwent liver resection in the Eastern Hepatobiliary Surgery Hospital cohort between January 2008 and December 2016 were divided into a training cohort and an internal validation cohort. In addition, 164 patients from Mengchao Hepatobiliary Hospital cohort between January 2014 and December 2016 served as an external validation cohort. The demographic information, and serological, MRI, and pathological data were obtained from each patient prior to and following surgery, followed by evaluating the model performance using the concordance index, time-dependent receiver operating characteristic curves, prediction error cures, and a calibration curve. A preoperative random survival forest (RSF) model and a postoperative RSF model were constructed based on the training set, which outperformed the conventional models, such as the Barcelona Clinic Liver Cancer (BCLC), the 8th edition of the American Joint Committee on Cancer (AJCC 8th) staging systems, and the Chinese stage systems. In addition, the preoperative and postoperative RSF models could also re-stratify patients with BCLC stage A/B/C or AJCC 8th stage IB/II/ⅢA/ⅢB or Chinese stage IB/IIA/ⅡB/ⅢA into low-risk, intermediate-risk, and high-risk groups in the training and the two validation cohorts. The preoperative and postoperative RSF models were effective for predicting recurrence in patients with huge HCC following hepatectomy.