T Cell-Associated Immunotherapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide with limited therapeutic options. Accumulating evidences suggest that immunotherapy could be a promising option for treating HCC. T cell-associated immunotherapy lights up the hope for the improvement of complementary approach to conventional HCC treatments, which needs further research to consummate the clinical consequences. The present work reviewed several T cells associated cellular immunotherapies for HCC, including immune checkpoint blockade, gene-engineered T cells, bispecific T cell engagers, and so on. We also analyzed how these immunotherapies can mediate tumor cell eradication and evaluated their superiority or insufficiency.

Long non-coding RNA PVT1 serves as a competing endogenous RNA for miR-186-5p to promote the tumorigenesis and metastasis of hepatocellular carcinoma.

Hepatocellular carcinoma is third leading cause of cancer-related death globally. Long non-coding RNA plasmacytoma variant translocation 1 has been reported to be dysregulated and plays a crucial role in various cancers. In this study, we investigated the interactions between plasmacytoma variant translocation 1 and miR-186-5p in the progression of hepatocellular carcinoma and explored the functional significance of plasmacytoma variant translocation 1. It was determined that plasmacytoma variant translocation 1 was significantly higher, while miR-186-5p was statistically lower in the hepatocellular carcinoma tissues than that in the adjacent normal tissues. Using gain-of-function and loss-of-function methods, our results revealed that plasmacytoma variant translocation 1 affected hepatocellular carcinoma cells proliferation, invasion, and migration. It was found that there was direct interaction between miR-186-5p and the binding site of plasmacytoma variant translocation 1 by performing dual-luciferase assay and RNA immunoprecipitation assay. Furthermore, it was identified that plasmacytoma variant translocation 1 regulated the expression of the miR-186-5p target gene, yes-associated protein 1. Taken together, plasmacytoma variant translocation 1 served as an endogenous sponge for miR-186-5p to reduce its inhibiting effect on yes-associated protein 1 and thus promoted the tumorigenesis of hepatocellular carcinoma.

Identifying the phase behavior of biodegradable poly(hexamethylene succinate-co-hexamethylene adipate) copolymers with FTIR.

Whether a phase separation or a cocrystallization occurs in poly(hexamethylene succinate-co-hexamethylene adipate) (P(HS-co-HA)) copolymers was studied with a combination of wide-angle X-ray diffraction (WAXD) and Fourier transform infrared (FTIR) spectroscopy. With HA as the majority, the presence of HS comonomers leads to weakening and broadening of (10l) peaks in the X-ray fiber diffraction patterns, while a crystal structure similar to PHS is formed in the copolymer with HS as the majority. The X-ray diffraction patterns imply possible cocrystallization between HS and HA comonomers, but cannot lead to an unambiguous conclusion, which was clarified with the compensative tool of FTIR. Following the characteristic absorption bands of crystals, cocrystallization of HS and HA comonomers was observed in copolymers with HA comonomer as the majority during which HA initiated the nucleation at high temperatures. With HA as minority, cocrystallization of HS and HA can still be achieved with a fast quenching to below 0 degrees C, while a phase separation occurs and only HS comonomer crystallizes at high temperatures. This demonstrates that P(HS-co-HA) has an asymmetric phase diagram. Because of the sensitivity to local conformations, FTIR spectroscopic method is demonstrated to be a powerful tool on study phase behaviors of polymers with similar crystal structure.

The Abnormal Expression of MicroRNA-542-3p in Hepatocellular Carcinoma and Its Clinical Significance.

AIM: To evaluate the expression of miRNA-542-3p in hepatocellular carcinoma, establish its function, and evaluate whether it could serve as a biomarker for diagnosis and prognosis of HCC patients. METHODS: qRT-PCR analysis was performed to determine the expression level of miRNA-542-3p in normal liver cells and HCC cell lines. Additionally, samples from TCGA consortium and from our patients were analyzed using biostatistical methods to ascertain whether miR-542-3p could be a good biomarker for HCC diagnosis and prognosis. The effects of miRNA-542-3p on HCC were investigated in HCCLM9 cells. RESULTS: The expression of miRNA-542-3p in HCC cells was significantly downregulated compared with normal liver cells. A lower level of expression of miRNA-542-3p was found in HCC tissue samples than in adjacent normal liver tissue samples from TCGA cases and our patients. Further evaluation revealed that the downregulation was clearly related to aggressive clinicopathological characteristics and affected the prognosis, as low-expressing patients tended to have shorter overall survival. Moreover, cell assays revealed that miR-542-3p overexpression inhibited HCC cell growth and induced apoptosis. CONCLUSION: We demonstrated for the first time that miRNA-542-3p appears to function as a novel tumor suppressor in HCC and may serve as a promising prognostic biomarker in HCC patients.

Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes tumorigenesis and metastasis by targeting miR-199a/b-5p in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is third leading cause of cancer-related death globally. Evidence suggest that long non-coding RNAs (lncRNAs) have emerged as key regulators of tumorigenesis and metastasis in HCC. In this study, we investigated the functional significance of SNHG12 and explored whether SNHG12 can directly interact with miR-199a/b-5p in the progression of HCC. METHODS: We determined the expression level of SNHG12 in HCC tissues with quantitative real-time PCR and then studied its clinical significance. The binding site between SNHG12 and miR-199a/b-5p was confirmed using dual luciferase assay and RNA immunoprecipitation (RIP) assay. SNHG12 was silenced through the siRNA transfection to determine whether SNHG12-siRNA is able to affect cell proliferation, invasion and metastasis. RESULTS: SNHG12 was significantly higher in the HCC tissues than that in the adjacent normal tissues. There were direct interactions between miR-199a/b-5p and the binding site of SNHG12. SNHG12 functioned as an endogenous sponge for miR-199a/b-5p to regulate the expression of MLK3 and affect the NF-κB pathway. CONCLUSION: SNHG12 may serve as a valuable biomarker and a potential therapeutic target for HCC.

Downregulation of long non-coding RNAs JPX and XIST is associated with the prognosis of hepatocellular carcinoma.

BACKGROUND: The expression profiles and biological relevance of long non-coding RNA XIST and its activator JPX in hepatocellular carcinoma (HCC) are not well elucidated. We measured JPX and XIST expression levels in HCC, evaluated their clinical significance in HCC progression, and verified their potential as biomarkers for diagnosing HCC. METHODS: JPX and XIST expression in 68 HCC tissues and adjacent normal tissues were evaluated by quantitative reverse transcription-PCR (qRT-PCR); their association with pathologic features and overall survival was analyzed. Plasma JPX/XIST levels in 42 patients with HCC and 68 healthy controls were measured by qRT-PCR to determine their potential as biomarkers. RESULTS: JPX and XIST levels were significantly decreased in HCC and associated with histological grade and tumor-node-metastasis stage (P<0.05). Low JPX and XIST expression resulted in significantly poor overall survival of HCC. Multivariate Cox regression analysis demonstrated that JPX/XIST expression levels were independent prognostic factors for HCC overall survival rates. Moreover, plasma JPX levels in patients were lower than that in controls; JPX yielded an area under the receiver operating characteristic curve of 0.814 and the combination of JPX and AFP possessed a promoted ability for discrimination between HCC patients and controls (AUC 0.905, 72.2% specificity, 97.1% sensitivity). CONCLUSIONS: Downregulated JPX and XIST may serve as novel biomarkers of poor prognosis in HCC.

Human Endogenous Retroviruses-K (HML-2) Expression Is Correlated with Prognosis and Progress of Hepatocellular Carcinoma.

Background. The association between human endogenous retroviruses-K (HERV-K) (HML-2) and human disease, including a variety of cancers, has been indicated. However, the function of HERV-K (HML-2) in the progression of hepatocellular carcinoma (HCC) still remains largely unclear. Methods. We detected the expression of HERV-K (HML-2) in 84 HCC tissues and adjacent nontumor tissues by quantitative real-time PCR (qRT-PCR) and analyzed its correlation with the clinical parameters. Result. The HEVR-K level was significantly increased in HCC compared with adjacent normal tissues (P < 0.01) which was proved to be significantly associated with cirrhosis (P < 0.05), tumor differentiation (P < 0.05), and TNM stage (P < 0.05). Moreover, the high expression of HERV-K (HML-2) had a poorer overall survival than patients with lower expression by a Kaplan-Meier survival analysis (P < 0.01). The multivariate Cox regression analysis indicated that the level of HERV-K (HML-2) was an independent prognostic factor for the overall survival rate of HCC patients. Receiver operating characteristic (ROC) curves demonstrated the diagnostic accuracy of HERV-K (HML-2) expression in HCC (AUC = 0.729, 74.7% sensitivity, and 67.8% specificity). Conclusions. Our results suggested that upregulation of HERV-K (HML-2) in HCC patients was significantly related to cancer progression and poor outcome, indicating that HERV-K (HML-2) might be a novel candidate prognostic biomarker for HCC.

A facile interfacial reaction route to prepare magnetic hollow spheres with tunable shell thickness.

Magnetic Fe3O4 hollow spheres were successfully synthesized with a water in oil in water (W/O/W) emulsion. During the facile procedure, no high pressure, high temperature, or other complex reaction conditions were required. Transmission electric microscope (TEM) images showed that all the hollow structural products have a good spherical morphology with an average diameter of 160 nm. The average size and the size distribution were further determined with dynamic light scattering (DLS), which reveals that the hollow nanospheres have a narrow size distribution. The average size from DLS was about 180 nm, which approximated that from TEM data. X-ray diffraction (XRD) demonstrates that the products were all Fe3O4 phase without any impurity. By increasing or decreasing the dosage of precipitate and precipitant sources, we controlled the shell thickness successfully in the tens of nanometers range. The formation mechanism of those hollow magnetic nanospheres was discussed by using the "reverse micelle transport" mechanism.