Purpose Vascular endothelial growth factor (VEGF) family members contribute greatly to the development and angiogenesis of hypervascular hepatocellular carcinoma (HCC). We have previously shown that Dicer inhibited HCC growth. In this study, we aimed to determine the relationship between Dicer and VEGF in HCC. Methods Gain-of-function studies were performed to determine the effect of different treatments on the proliferation, migration, and invasion of HCC cells. Expression of VEGF-A in xenograft tumor tissues was analysed using Western blotting, and that of CD31 using immunohistochemical analysis. Results We found that Dicer inhibited proliferation, migration and invasion of HCC cells by suppressing VEGF-A expression. Interestingly, VEGF-A165, which is the most prominent VEGF-A isoform, counteracted Dicer-induced inhibition of HCC cells. In addition, a monoclonal anti-VEGF antibody (bevacizumab) enhanced Dicer-induced inhibition of HCC in vitro and in vivo. Further, immunohistochemical analysis of CD31 indicated bevacizumab and Dicer synergized to reduce tumor microvessel density. Conclusion Our data demonstrated that Dicer enhanced bevacizumab-related inhibition of HCC cell via the VEGF pathway; therefore, Dicer in coordination with bevacizumab may provide another potential approach for HCC therapy.

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Background Immune checkpoint inhibitors (ICIs) has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate immune related adverse events (irAEs) in patients. Some studies have shown that there is a close relationship between the occurrence of irAEs and prognosis. In present study, we have attempted to establish whether the occurrence of irAEs after the use of anti PD-1 antibodies is associated with treatment efficacy in people with advanced gastric cancer (AGC). Methods This study included patients treated with the anti-PD-1 antibodies for AGC patients at The Fourth Hospital of Hebei Medical University. IrAEs were identified clinically and graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.03. Efficacy was evaluated with objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS). The analysis was performed to determine the association between irAEs and clinical outcomes. Result Of the 74 AGC patients in our study, 24 developed irAEs. The DCR of the irAE displayed a trend better than that of non-irAE group but without statistical difference (41.70% VS 6.0%, p = 0.118). Median PFS in the irAE group was superior to that in the non-irAE group (176 days VS 94 days, p = 0.001). Median OS also showed this trend of difference at borderline statistical level (292 days VS 239 days, p = 0.057). Multivariate analysis also demonstrated irAE (HR = 0.269, 95%CI: 0.088 to 0.822, p = 0.021) were associated independently with the better prognosis for AGC patients. Conclusion In advanced gastric cancer treated with anti PD-1 antibodies, the occourence of irAEs might contribute to the improved prognosis.

Background: Elevated level of interleukin-8 (IL-8) promotes hepatocellular carcinoma (HCC) development and contributes to poor prognosis. Previously, we have proved that Dicer inhibits HCC progression. In this study, we evaluated the potential interaction between IL-8 and Dicer as well as their influence on HCC. Methods: Hepatocellular carcinoma cells of SMMC-7721 were divided into 2 groups for subsequent analysis: pCMV-Dicer group for Dicer-overexpressing lentivirus transfected cells (pCMV-Dicer cells) and pCMV-NC group for empty lentivirus transfected cells (pCMV-NC cells). Cell Counting kit-8 (CCK8), wound healing, and transwell were used to evaluate the inhibitory effect of Dicer overexpression on proliferation, migration, and invasion of HCC cells. The level of IL-8 was measured by flow cytometry bead-based immunoassays. Male nude BALB/c mice injected with pCMV-Dicer or pCMV-NC cell suspensions was used for transplant of HCC tumor. Results: We found that the secretion of IL-8 was reduced in the medium of pCMV-Dicer cells ( P = .027). Recombinant human IL-8 (rhIL-8) reversed the inhibitory effect of Dicer on proliferation ( P < .01), migration ( P = .003), and invasion ( P = .001), whereas IL-8 inhibitor of reparixin enhanced inhibitory effect of Dicer on proliferation ( P < .05), migration ( P = .008), and invasion ( P = .000). Lenvatinib downregulated the IL-8 level of HCC cells ( P = .000) as well as promote Dicer-induced inhibition for HCC cells referring to proliferation ( P < .05), migration ( P = .000), and invasion ( P = .000). Animal experiments also demonstrated that Dicer cooperated with lenvatinib to inhibit the growth of HCC tumors ( P < .05). Conclusions: Dicer cooperated with lenvatinib to inhibit HCC growth via downregulating IL-8, and Dicer displayed its potential capability to enhance the anti-tumor effect of lenvatinib.

Rheumatoid arthritis (RA) is a complex, heterogeneous, progressive and long-term autoimmune disease characterized by symmetrical joint inflammation and bone erosion. The etiology of RA is unclear, but its pathogenesis is associated with oxidative stress and inflammatory cytokines. Single nucleotide polymorphisms (SNPs) in the microRNA (miRNA)-binding sites modify the development of rheumatic disease by regulating the expression of target genes. The present study investigated whether SNPs in the miRNA binding site in the 3' untranslated region (3'-UTR) of SET domain containing lysine methyltransferase) 8 (SET8) and Keratin 81 (KRT81), namely rs16917496 and rs3660, respectively, were associated with the occurrence of RA. The polymerase chain reaction-ligase detection reaction assay showed that the distribution frequencies of the CC genotype (P=0.025) of SNP rs16917496 in SET8 were significantly higher in patients with RA than in healthy controls, which indicated that the CC genotype was associated with an increased risk of RA. SET8 expression in the blood samples of CC genotype carriers was lower than that of TT genotype carriers. Moreover, the CC genotype carriers exhibited higher reactive oxygen species (ROS) levels (1011.500±536.426 vs. 548.616±190.508, P=0.032) and lower interleukin-10 (IL-10) levels (P<0.001). The present study demonstrated that SNP rs16917496 in the 3'-UTR of SET8 was a predictor of RA risk and may regulate RA development by mediating expression of SET8, thereby regulating the levels of ROS and IL-10.

Background: Inflammatory cytokines are related to the occurrence and development of hepatocellular carcinoma (HCC). Objectives: Interleukin 6 (IL-6) is associated with the occurrence and prognosis of HCC, while Dicer inhibits HCC; accordingly, we checked whether Dicer regulates HCC by modulating the IL-6 pathway. Methods: The HCC cells of SMMC-7721 transfected with Dicer overexpression (pCMV-Dicer) and control (pCMV-NC) lentivirus were divided into 3 groups: The SMMC-7721, pCMV-NC, and pCMV-Dicer groups. The assays of cell proliferation, migration, and invasion were performed using cell counting, wound scratch, and transwell chamber assay. The IL-6 level was measured by flow cytometry bead-based immunoassays. All statistical analyses were analyzed using SPSS version 21 by the student t test and 1-way analysis of variance (ANOVA). Results: Dicer inhibited the secretion of IL-6 from HCC cells, as well as the growth of HCC related to proliferation, migration, and invasion. IL-6 incubation with pCMV-NC cells increased proliferation (from 24 hours to 72 hours; P < 0.05), migration (P = 0.008), and invasion (P = 0.85). In addition, IL-6 could reverse the inhibitory effect of Dicer on HCC cells related to proliferation (P < 0.01) and migration (P = 0.006) when incubated with pCMV-Dicer cells, whereas an IL-6 blocker of tocilizumab could enhance the Dicer-induced inhibition related to proliferation (P < 0.05), migration (P = 0.007), and invasion (P = 0.001) when incubated with pCMV-Dicer cells. Furthermore, Dicer could increase the inhibition efficiency of apatinib on HCC treatment by their cooperation in IL-6 downregulation. Conclusions: Dicer could inhibit HCC by the IL-6 pathway, which would be a potential target for HCC treatment. The Dicer inducer might be an enhancer of apatinib for HCC treatment.

Background Immune checkpoint inhibitors (ICIs) has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate immune related adverse events (irAEs) in patients. Some studies have shown that there is a close relationship between the occurrence of irAEs and prognosis. In present study, we have attempted to establish whether the occurrence of irAEs after the use of anti PD-1 antibodies is associated with treatment efficacy in people with advanced gastric cancer (AGC). Methods This study included patients treated with the anti-PD-1 antibodies for AGC patients at The Fourth Hospital of Hebei Medical University. IrAEs were identified clinically and graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.03. Efficacy was evaluated with objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS). The analysis was performed to determine the association between irAEs and clinical outcomes. Result Of the 74 AGC patients in our study, 24 developed irAEs. The DCR of the irAE displayed a trend better than that of non-irAE group but without statistical difference (41.70% VS 6.0%, p = 0.118). Median PFS in the irAE group was superior to that in the non-irAE group (176 days VS 94 days, p = 0.001). Median OS also showed this trend of difference at borderline statistical level (292 days VS 239 days, p = 0.057). Multivariate analysis also demonstrated irAE (HR = 0.269, 95%CI: 0.088 to 0.822, p = 0.021) were associated independently with the better prognosis for AGC patients. Conclusion In advanced gastric cancer treated with anti PD-1 antibodies, the occourence of irAEs might contribute to the improved prognosis.