MicroRNA-188-5p inhibits hepatocellular carcinoma proliferation and migration by targeting forkhead box N2.

BACKGROUND: This study aimed to identify the biological functions, expression modes, and possible mechanisms underlying the relationship between metastatic human hepatocellular carcinoma (HCC) and MicroRNA-188-5p (miR-188) dysregulation using cell lines. METHODS: A decrease in miR-188 was detected in low and high metastatic HCC cells compared to that in normal hepatic cells and non-invasive cell lines. Gain- and loss-of-function experiments were performed in vitro to investigate the role of miR-188 in cancer cell (Hep3B, HepG2, HLF, and LM3) proliferation and migration. RESULTS: miR-188 mimic transfection inhibited the proliferation of metastatic HLF and LM3 cells but not non-invasive HepG2 and Hep3B cells; nonetheless, miR-188 suppression promoted the growth of HLF and LM3 cells. miR-188 upregulation inhibited the migratory rate and invasive capacity of HLF and LM3, rather than HepG2 and Hep3B cells, whereas transfection of a miR-188 inhibitor in HLF and LM3 cells had the opposite effects. Dual-luciferase reporter assays and bioinformatics prediction confirmed that miR-188 could directly target forkhead box N2 (FOXN2) in HLF and LM3 cells. Transfection of miR-188 mimics reduced FOXN2 levels, whereas miR-188 inhibition resulted in the opposite result, in HLF and LM3 cells. Overexpression of FOXN2 in HLF and LM3 cells abrogated miR-188 mimic-induced downregulation of proliferation, migration, and invasion. In addition, we found that miR-188 upregulation impaired tumor growth in vivo. CONCLUSIONS: In summary, this study showed thatmiR-188 inhibits the proliferation and migration of metastatic HCC cells by targeting FOXN2.

Correlation between immune-related adverse events and long-term outcomes in pembrolizumab-treated patients with unresectable hepatocellular carcinoma: A retrospective study.

BACKGROUND: Although immune checkpoint inhibitor (ICI) therapy has improved the prognosis of unresectable hepatocellular carcinoma (HCC), it has also resulted in unique immune-related adverse events (irAEs). The relationship between irAE and treatment outcomes in ICI-treated unresectable HCC patients remains unknown. AIM: To elucidate the correlation between immune-related toxic effects and prognosis in patients with unresectable HCC treated with pembrolizumab. METHODS: From March 2019 to February 2021, a total of 190 unresectable HCC (Barcelona Clinic Liver Cancer C) patients receiving pembrolizumab treatment were retrospectively reviewed. Overall survival (OS) was the primary endpoint, while objective response rate (ORR), disease control rate (DCR), and time to progression (TTP) were secondary evaluation indexes. We assessed demographics, irAEs, and outcomes by retrospective review. RESULTS: One hundred and forty-three males and 47 females were included in the study. The ORR and DCR were 12.1% (23/190) and 52.1% (99/190), respectively. The median OS was 376 d [95% confidence interval (CI): 340-411 d] and the median TTP was 98 d (95%CI: 75-124 d). The overall incidence of treatment-related adverse events was 72.6% (138/190) and 10.0% of them were severe irAEs (grade ≥ 3). Child-Pugh B class, portal vein tumor thrombus, extrahepatic metastasis, and hypothyroidism were the independent risk factors for survival. Patients with hypothyroidism showed a longer OS [517 d (95%CI: 423-562) vs 431 d (95%CI: 412-485), P = 0.011] and TTP [125 d (95%CI: 89-154) vs 87 d (95%CI: 61-98), P = 0.004] than those without irAEs. CONCLUSION: Pembrolizumab-treated patients with unresectable HCC who experienced hypothyroidism have promising ORR and durable response. Hypothyroidism, an irAE, may be used as a clinical evaluation parameter of response to ICIs in unresectable HCC.

Anatomic resection improved the long-term outcome of hepatocellular carcinoma patients with microvascular invasion: A prospective cohort study.

BACKGROUND: The long-term effect of anatomic resection (AR) is better than that of non-anatomic resection (NAR). At present, there is no study on microvascular invasion (MVI) and liver resection types. AIM: To explore whether AR improves long-term survival in patients with hepatocellular carcinoma (HCC) by removing the peritumoral MVI. METHODS: A total of 217 patients diagnosed with HCC were enrolled in the study. The surgical margin was routinely measured. According to the stratification of different tumor diameters, patients were divided into the following groups: ≤ 2 cm group, 2-5 cm group, and > 5 cm group. RESULTS: In the 2-5 cm diameter group, the overall survival (OS) of MVI positive patients was significantly better than that of MVI negative patients (P = 0.031). For the MVI positive patients, there was a statistically significant difference between AR and NAR (P = 0.027). AR leads to a wider surgical margin than NAR (2.0 ± 2.3 cm vs 0.7 ± 0.5 cm, P < 0.001). In the groups with tumor diameters < 2 cm, both AR and NAR can obtain a wide surgical margin, and the surgical margins of AR are wider than that of NAR (3.5 ± 5.8 cm vs 1.6 ± 0.5 cm, P = 0.048). In the groups with tumor diameters > 5 cm, both AR and NAR fail to obtain wide surgical margin (0.6 ± 1.0 cm vs 0.7 ± 0.4 cm, P = 0.491). CONCLUSION: For patients with a tumor diameter of 2-5 cm, AR can achieve the removal of peritumoral MVI by obtaining a wide incision margin, reduce postoperative recurrence, and improve prognosis.

Effect of organic fractions on sorption properties of organic pollutants in sediments.

Humic substrates are a major fraction of sediment organic matters, and the sorption of hydrophobic organic chemicals by humic substrates influences their behavior and fate in sediment. In this paper, organic matters were divided into non-humic substrates and humic substrates. Non-humic substrates include acid leaching fraction, acid extracted fraction, and lipid; humic substrates were fractionated into Ca-binding-FA (fulvic acid), Ca-binding-HA (humic acid), oxide-FA, oxide-HA, and humin. To study the effect of organic fractions on sorption properties, sorption kinetic and equilibrium sorption experiments of phenanthrene and pentachlorophenol (PCP) in five sediments were carried out. The results showed that the contents of acid leaching fraction and oxide-binding-HA were the main fractions to affect the sorption rate constant, and for the sorption capacity of phenanthrene, humin was the major fraction, followed by oxide-binding-HA, oxide-binding-FA, and so on. While for PCP, the factors of influence on sorption capacity were mainly CEC, Ca-binding-FA, and Ca-binding-HA.

Binding of pyrene to dissolved organic matters: fractionation and characterization.

Based on a modified Leenheer DOM fractionation scheme, fractionation of DOM from the paddy soil was conducted by using XAD-8 resin into hydrophobic bases (HOB), hydrophobic acids(HOA), acid-insoluble matter (AIM), hydrophobic neutrals (HON) and hydrophilic matter (HIM). In total carbon content of DOM, 35.32% were the HIM and only 0.73% the HOB. However, HOA and AIM altogether occupied 53.45%, while the HON fraction represented 10%. The sorption experiments were conducted to determine the sorption capacity of pyrene on unfractionated DOM and its fractions. Elemental analysis, 1H-NMR and FTIR spectra were carried out on unfractionated DOM and its fractions to examine the relationship between the structure of DOM and partition coefficients (K(oc)). The results showed that HON had a greater affinity for binding pyrene than other fractions. While HON was characterized by large long-chain alkylate (aliphatic structure). AIM exhibited relative higher K(oc) values than HOA and HIM, due to much aromatic structure in AIM, while the high content of carboxylic groups of HOA and HIM depressed their binding capacity. This study demonstrated HON is a key subcomponents of DOM in binding of pyrene, in other words, aliphalic structure in DOM play an important role in binding of pyrene.

[Fractionation and spectroscopic property of dissolved organic matters in soils].

Based on a modified Leenheer DOM fractionation sche me, fractionation of DOM from paddy soils was conducted byusing XAD-8 resin into hydrophobic bases (HOB), hydrophobic acids (HOA), acid-insoluble matter (AIM), hydrophobic neutrals (HON) and hydrophillic matter (HIM), and their structural characteristics were studied by means of elemental composition, FTIR and 1H-NMR spectroscopy. The fractionation scheme used here provided a preferable separation of the fractions in terms of hydrophobicity and a high recovery. Of the DOC extracted from the soils, the HOB was the least fraction, accounting for 0.73%-3.83%, and the HIM fraction was the largest, accounting for 36%-42%. The HON fraction represented 7%-15%. The relative content of the HOA plus AIM was about 50%. Separated by this technique, the large-chain alkylate and the major portion of the N components mainly characterized HON, while the HOA fraction contained a large amount of carboxyl groups but less amount of aromatic groups with a higher quantity of carbohydrates compared to that of FA. AIM fraction was dominated by high branched (n value) polyphenols and humus bound carbohydrates. HIM was characterized by considerable amount of carboxyl and carbohydrates.