Docosahexaenoic acid (DHA) plays an important role in suppressing the growth of cancer. In this paper, the synergetic anticancer effect of combination DHA with 5-fluorouracil (5-FU) was investigated in gastric carcinoma cells. We found that DHA inhibited the growth of cultured SGC7901 cells at different concentrations in a dose- and time-dependent manner. Furthermore, the growth-inhibition activities of increasing concentration of 5-FU were markedly enhanced when different doses of 5-FU were administered in the combination with dose as low as 40 microg/ml of DHA. The early phase of apoptosis was increased in DHA- and 5-FU-treated cells. In the case of apoptotic genes expression in the combination-treated cells, BAX mRNA expression increased, whereas FAS, BCL-2, BCL2L12, and CASPASE-9 mRNA expression decreased. These results suggest that DHA strongly enhances the anticancer effect of 5-FU. Moreover, the application of both compounds on gastric cancer cells provides a new potential approach for cancer therapy.

Background. Gastric cancer (GC) is one of the global mortality diseases and has a poor prognosis due to the lack of ideal tumor biomarkers. Numerous studies have shown that long noncoding RNAs (lncRNAs) can affect the occurrence and development of cancer through a variety of signaling pathways. The abnormal expression and specificity of lncRNAs in tumors make them potential biomarkers of cancers. Nevertheless, the diagnostic roles of lncRNAs in GC have been poorly understood. So this study focuses on the clinical diagnostic value of lncRNAs in GC. Materials and Methods. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to investigate the expression of the linc-ROR (long intergenic noncoding RNA, regulator of reprogramming) in 105 paired GC tissues and adjacent normal tissues. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were established to assess the diagnostic value of linc-ROR. The relationship between expression of linc-ROR and clinicopathological factors of patients with GC was further explored. Kaplan-Meier analysis was performed to evaluate the prognostic value of linc-ROR expression. Results. The linc-ROR expression level was significantly decreased in GC tissues compared with its adjacent nontumor tissues ( n = 105 , P < 0.001 ). We also discovered that linc-ROR was evidently downregulated in 68.6% (72/105) of GC tissues. The AUC’s value of linc-ROR was up to 0.6495, with sensitivity and specificity of 0.7524 and 0.5143, respectively. Intriguingly, the linc-ROR expression levels were obviously associated with tumor differentiation ( P = 0.004 ). Notably, the overall survival rate of GC patients with high expression of linc-ROR was significantly higher than those with low expression. Conclusion. Our data revealed that linc-ROR has clinical potential as a biomarker for the diagnosis of GC and assessment of its prognosis.

Natural killer (NK) cells are the critical elements of the innate immune response and implicated in rapidly recognizing and eliminating cancer cells. However, the tumorsuppressive ability of NK cells is often impaired in several cancer types. The critical roles of microRNAs have been elucidated by increasing evidences, while the regulation of miR-338-3p in anti-tumor activation of NK cells and its relationship with estrogen in breast cancer (BC) are still confusing. Here, miR-338-3p level was found to be significantly downregulated in BC tissues and estrogen receptor positive (ER + ) cells, this difference was more obvious in ER + patients or BC patients at advanced stage (TNM III and IV). MiR-338-3p level was shown to be downregulated by 17β-estradiol in BC cells (MDA-MB-231 cells and MCF-7) in vitro. MiR-338-3p overexpression decreased disintegrin and metalloprotease-17 (ADAM17) secretion in MDA-MB-231 (ER À ) and MCF-7 (ER + ) cells. In addition, miR-338-3p overexpression or treatment with anti-ADAM17 antibody could down-regulate granzyme B, CD16, and NKG2D in NK cells, which was reversed by human recombinant ADAM17. Furthermore, these educated NK cells could promote the viability of MDA-MB-231 or MCF-7 cells. Taken together, our results demonstrate that miR-338-3p was negatively regulated by estrogen in BC cells, impairing NK cell's activity by the upregulation of ADAM17, and conversely promoted the viability of BC cells. Therefore, the estrogen/miR-338-3p/ADAM17 axis is critically implicated in BC pathogenesis and may provide potential targets for BC diagnosis and treatment.

Background: Laminin subunit betas (LAMBs) are the major noncollagenous constituent of basement membranes that implicated in biological functions such as cell adhesion, metastasis. However, few studies have systematically analyzed the prognostic value and immune characteristics of LAMBs in pan-cancer types. Methods: A pan-cancer comprehensive analysis of LAMBs in expression levels, protein localization, structure, mutations and methylation were explored. Next, Cox regression and Kaplan-Meier method were applied to analyze the prognostic role of LAMBs in pan-cancer. Protein-Protein Interaction (PPI) analysis was performed in the GeneMANIA database, and enrichment analysis was predicted signaling pathways were identifified by using Gene Ontology (GO), Kyoto Encyclopedia of Genes (KEGG) and gene set variation analysis (GSVA) analysis. The immune characteristics of LAMBs in the tumor microenvironment were evaluated via ImmuCellAI and TIMER 2.0. was the main platform to investigate the tumor associated macrophages (TAMs) related to LAMBs in pan-cancer, especially M2-like TAMs. In addition, single-cell sequencing analysis and tracking tumor immunophenotype (TIP) were also conducted to validate the interaction immune role of LAMBs with macrophages in cancers. Furthermore, the immunoregulators, tumour mutational burden (TMB) and microsatellite instability (MSI) was performed to evaluate the immune response role of LAMBs in cancers. Finally, the immunotherapy response and drug sensitive small molecule drugs based on LAMBs expression were predicted. Results: The expression, mutation and methylation of LAMBs was aberrantly expressed in most cancer types and exhibited prognosis predictive ability in various cancers. In addition, our results also showed that LAMBs was signifificantly correlated with immune-activated (including pathways and biological processes), immune cell infifiltrations, immunoregulator expressions, TMB and MSI. Importantly, analysis of an independent immunotherapy cohorts revealed that low-risk patients had better immunotherapy responses and prognosis than high-risk patients in some cancers. Furthermore, the immunotherapy response and sensitive small molecule drugs which correlate with LAMBs expression in different cancer types, had a potent capability to predict immunotherapy response in pan-cancers. Conclusions: LAMBs expression may contribute to increased infiltration of TAMs, which not only acted as a potent prognostic factor to predict the clinical outcomes of cancer patients but was also a promising immunotherapy predictive biomarker for cancer patients treated with immune-checkpoint inhibitors (ICIs).