Non-small cell lung cancer (NSCLC) is one of the major causes of morbidity and mortality worldwide. We aimed to investigate the role of N6-methyladenosine (m6A) methyltransferase-like 3 (METTL3) regulating microRNA-1246 (miR-1246) in the progression of NSCLC by targeting paternally expressed gene 3 (PEG3). METTL3, miR-1246, and PEG3 expression in tissues was assessed, and the predictive role of METTL3 in prognosis of patients with NSCLC was detected. NSCLC cells were relatively treated with altered expression of METTL3, miR-1246, or PEG3 to measure their roles in the proliferation, migration, invasion, apoptosis, and in vivo growth of the NSCLC cells. The RNA m6A level was determined, and the targeting relationship between miR-1246 and PEG3 was confirmed. Our results revealed that METTL3 and miR-1246 were upregulated, whereas PEG3 was downregulated in NSCLC tissues. METTL3 knockdown or PEG3 overexpression in NSCLC cells suppressed malignant behaviors of NSCLC cells. METTL3 affected the m6A modification of miR-1246, thus upregulating miR-1246 and miR-1246-targeted PEG3. The elevation of PEG3 reversed the effects of miR-1246 upregulation on NSCLC cells. This study revealed that m6A methyltransferase METTL3 affects the m6A modification of miR-1246, thus upregulating miR-1246 to promote NSCLC progression by inhibiting PEG3.

Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare subtype of lung cancer that is associated with the Epstein-Barr virus in Asia. Due to the lack of prospective studies, the best first-line treatment and survival outcomes remain unclear. Herein, This study investigated the efficacy and safety of different treatment regimens for advanced pLELC. This retrospective study included 68 patients with advanced pLELC from two centers in China. Patients were divided into three groups according to different first-line treatments: chemotherapy (n=49, 72.1%), immunotherapy (n=7, 10.3%), and chemoimmunotherapy (n=12,17.6%). The primary endpoint of this study was the 2-year progression-free survival (PFS) of each group. The results show that the median PFS was 6.9 months (range, 2.3–not estimable) in the chemotherapy group, 11.0 months (range, 2–not estimable) in the immunotherapy group, and 11.8 months (range, 6–not estimable) in the chemoimmunotherapy group. There was a significant difference in 2-year PFS between the chemoimmunotherapy group and the chemotherapy group (hazard ratio, 0.38, 95% confidence interval: 0.18-0.78, log-rank P=0.007). The most frequent grade 3-4 adverse event in the chemotherapy and chemoimmunotherapy groups was myelosuppression (10/49 [22.4%] and 4/12 [33.3%], respectively). The most frequent grade 3-4 adverse events in the immunotherapy group were diarrhea (1/7, 14.8%) and hepatotoxicity (1/7, 14.8%). Chemoimmunotherapy had the highest 2-year PFS as a first-line treatment for advanced pLELC compared to chemotherapy and immunotherapy. This study suggests that chemoimmunotherapy may be the best first-line treatment for patients with advanced pLELC.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide. Although advances have made in treatment of HCC, the overall survival rate remains low and the molecular pathogenesis of HCC is still poorly understood. The purpose of this study was to explore the molecular pathogenesis of HCC. A total of 89 patients were involved in the study. MicroRNA-93 (miR-93) was aberrantly up-regulated in HCC tissues as determined by qRT-PCR. The high level of miR-93 was closely associated with larger tumor size (p < 0.05) and poor overall survival (p < 0.05). In in vitro and in vivo assays, we demonstrated that high miR-93 levels enhanced cell growth of HCC. The luciferase activity assay showed that PDCD4 was a direct target of miR-93 and its expression was down-regulated by miR-93. Re-expression of PDCD4 inversely correlated with the level of miR-93 and attenuated the miR-93-induced promotion of cell growth in HCC. Taken together, our data indicate that miR-93 may function as an oncogenic factor in HCC, and promotes HCC cell proliferation by targeting PDCD4.

Background Sepsis is a systemic inflammatory response that can lead to the dysfunction of many organs. The aberrant expression of miRNAs is associated with the pathogenesis of sepsis. However, the biological functions of miR-128-3p in sepsis remain largely unknown, and its mechanism should be further investigated. This study aimed to determine the regulatory network of miR-128-3p and TGFBR2 in lipopolysaccharide (LPS)-induced sepsis. Methods The expression levels of miR-128-3p and transforming growth factor beta receptors II (TGFBR2) were detected by quantitative polymerase chain reaction (qPCR). The protein levels of TGFBR2, Bcl-2, Bax, cleaved caspase 3, Smad2, and Smad3 were measured by western blot. Cell apoptosis was analyzed by flow cytometry. Cytokine production was detected by enzyme-linked immunosorbent assay (ELISA). The binding sites of miR-128-3p and TGFBR2 were predicted by Targetscan online software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results The level of miR-128-3p was decreased, and TGFBR2 expression was increased in serum samples of sepsis patients and LPS-induced HK2 cells. Overexpression of miR-128-3p or knockdown of TGFBR2 ameliorated LPS-induced inflammation and apoptosis. Moreover, TGFBR2 was a direct target of miR-128-3p, and its overexpression reversed the inhibitory effects of miR-128-3p overexpression on inflammation and apoptosis in LPS-induced HK2 cells. Besides, overexpression of miR-128-3p downregulated TGFBR2 to suppress the activation of the Smad signaling pathway. Conclusion miR-128-3p could inhibit apoptosis and inflammation by targeting TGFBR2 in LPS-induced HK2 cells, which might provide therapeutic strategy for the treatment of sepsis.

Background: The aim of this research was to evaluate the effect of spatial location of tumors on the prognosis of patients with left upper lung non-small cell lung cancer (NSCLC), with a focus on the S1+2+3 and lingual segment.Methods: A total of 486 patients who underwent lobectomy and systematic lymph node dissection were collected retrospectively in this study (354 S1+2+3 and 132 lingual segment patients). Factors impacting survival were assessed via univariate analyses, multivariate analyses, and log-rank tests.Results: Compared with tumor location in S1+2+3, lingual segment tumor location of stage II to III left upper lung NSCLC patients was significantly associated with a better 5-year disease-free survival (DFS) (P=0.041). Multivariate analysis results showed that tumor location in the lingual segment was a good independent prognostic factor of stage II to III left upper lung NSCLC patients [hazard ratio (HR) =0.602, 95% confidence interval (CI): 0.149-0.865, P=0.006). However, in stage I left upper lung NSCLC, tumor location (HR =1.069, 95% CI: 0.571-2.000, P=0.835) was not an independent prognostic factor, and only T2 (HR =2.422, 95% CI: 1.271-4.620, P=0.007) was an independent worse prognosis factor.Conclusions: Tumor location in the lingual segment of left upper lung stage II to stage III NSCLC is a good independent prognostic factor compared with S1+2+3. Nevertheless, tumor location does not impact the prognosis of patients with stage I NSCLC in the left upper lung.

No abstract

Immune cells and immune microenvironment play important in the evolution of sepsis. This study aimed to explore hub genes related to the abundance of immune cell infiltration in sepsis. The GEOquery package is used to download and organize data from the GEO database. A total of 61 differentially expressed genes (DEGs) between sepsis samples and normal samples were obtained through the ‘limma’ package. T cells, natural killer (NK) cells, monocytes, megakaryocytes, dendritic cells (DCs), and B cells formed six distinct clusters on the t-distributed stochastic neighbor embedding (t-SNE) plot generated using the Seurat R package. Gene set enrichment analysis (GSEA) enrichment analysis showed that sepsis samples and normal samples were related to Neutrophil Degranulation, Modulators of Tcr Signaling and T Cell Activation, IL 17 Pathway, T Cell Receptor Signaling Pathway, Ctl Pathway, Immunoregulatory Interactions Between a Lymphoid and A Non-Lymphoid Cell. GO analysis and KEGG analysis of immune-related genes showed that the intersection genes were mainly associated with Immune-related signaling pathways. Seven hub genes (CD28, CD3D, CD2, CD4, IL7R, LCK, and CD3E) were screened using Maximal Clique Centrality, Maximum neighborhood component, and Density of Maximum Neighborhood Component algorithms. The lower expression of the six hub genes (CD28, CD3D, CD4, IL7R, LCK, and CD3E) was observed in sepsis samples. We observed the significant difference of several immune cell between sepsis samples and control samples. Finally, we carried out in vivo animal experiments, including Western blotting, flow cytometry, Elisa, and qPCR assays to detect the concentration and the expression of several immune factors.