Sevoflurane attenuates proliferative and migratory activity of lung cancer cells via mediating the microRNA-100-3p/sterol O-Acyltransferase 1 axis.

Recently, evidence has shown that microRNA-100-3p (miR-100-3p) has been revealed as a tumor suppressor in diverse human diseases, while its capability in lung cancer warrants further validation. In this work, we aimed to discuss the impact of sevoflurane on biological functions of lung cancer cells by modulating the miR-100-3p/sterol O-acyltransferase 1 (SOAT1) axis. Lung cancer cell lines (A549 and H460) were treated with various concentrations of sevoflurane. Cell viability, proliferation, migration, and invasion were evaluated using MTT, colony formation, wound healing, and transwell assays. Moreover, miR-100-3p and SOAT1 expressions were evaluated by reverse transcription-quantitative polymerase chain reaction in lung cancer cells. The target interaction between miR-100-3p and SOAT1 was predicted by bioinformatics analysis and verified by the dual-luciferase reporter gene assay. The findings of our work demonstrated that sevoflurane impeded the abilities on viability, proliferation, migration, and invasion of A549 and H460 cells. The expression of miR-100-3p was reduced, and SOAT1 expression was elevated in lung cancer cells. miR-100-3p targeted SOAT1. Besides, sevoflurane could lead to expressed improvement of miR-100-3p or limitation of SOAT1. Downregulation of miR-100-3p or upregulation of SOAT1 restored the suppression of sevoflurane on abilities of viability, proliferation, migration, and invasion in A549 and H460 cells. In the rescue experiment, downregulation of SOAT1 reversed the impacts of downregulation of miR-100-3p on sevoflurane on lung cancer cells. Collectively, our study provides evidence that sevoflurane restrained the proliferation and invasion in lung cancer cells by modulating the miR-100-3p/SOAT1 axis. This article provides a new idea for further study of the pathogenesis of lung cancer.

Combined analysis of gut microbiome and serum metabolomics reveals novel biomarkers in patients with early-stage non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer and is one of the most fatal cancers worldwide. Recently, the International Association for the Study of Lung Cancer (IASLC) proposed a novel grading system based on the predominant and high-grade histological patterns for invasive pulmonary adenocarcinoma (IPA). To improve outcomes for NSCLC patients, we combined serum metabolomics and fecal microbiology to screen biomarkers in patients with early-stage NSCLC and identified characteristic microbial profiles in patients with different grades of IPA. 26 genera and 123 metabolites were significantly altered in the early-stage NSCLC patients. Agathobacter, Blautia, Clostridium, and Muribaculacea were more abundant in the early-stage NSCLC patients compared with healthy controls. For the different grades of IPA, the characteristic microorganisms are as follows: Blautia and Marinobacter in IPA grade type 1; Dorea in IPA grade type 2; and Agathobacter in IPA grade type 3. In the metabolome results, the early-stage NSCLC group mainly included higher levels of sphingolipids (D-erythro-sphingosine 1-phosphate, palmitoyl sphingomyelin), fatty acyl (Avocadyne 1-acetate, 12(S)-HETE, 20-Carboxy-Leukotriene B4, Thromboxane B3, 6-Keto-prostaglandin f1alpha, Sebacic acid, Tetradecanedioic acid) and glycerophospholipids (LPC 20:2, LPC 18:0, LPC 18:4, LPE 20:2, LPC 20:1, LPC 16:1, LPC 20:0, LPA 18:2, LPC 17:1, LPC 17:2, LPC 19:0). Dysregulation of pathways, such as sphingolipid metabolism and sphingolipid signaling pathway may become an emerging therapeutic strategy for early-NSCLC. Correlation analysis showed that gut microbiota and serum metabolic profiles were closely related, while Muribaculacea and Clostridium were the core genera. These findings provide new biomarkers for the diagnosis of early-stage NSCLC and the precise grading assessment of prognostic-related IPAs, which are of clinical importance and warrant further investigation of the underlying molecular mechanisms.

Technical aspects and early results of uniportal video-assisted thoracoscopic complex segmentectomy: a 30 case-series study.

BACKGROUND: With the advantages of better cosmetic incision and faster recovery, uniportal video-assisted thoracoscopic surgery (UP-VATS) has developed rapidly worldwide in recent decades, and indications for UP-VATS have been further expanded to those for conventional VATS. Complex segmentectomy that makes several or intricate intersegmental planes, with more complex procedures, continues to be difficult in minimally invasive techniques. However, there are few reports on UP-VATS complex segmentectomy. In this report, we describe the perioperative clinical data and operative techniques and present our early results of UP-VATS complex segmentectomy in our hospital. METHODS: The records of a total of 30 patients who underwent UP-VATS complex segmentectomy by a single surgeon between January 2021 and June 2021 were retrospectively reviewed. We defined cases as complex segmentectomy if they required resection of segments 9 and 10, combined segmentectomy, segmentectomy + subsegmentectomy, subsegmentectomy, or combined subsegmentectomy. RESULTS: The mean age was 52.8 ± 9.9 years old; the mean nodule size was 0.84 ± 0.36 cm; the mean margin width was 2.307 ± 0.309 cm; the median operative time was 229.0 ± 58.06 min; the mean operative hemorrhage was 56.60 ± 17.95 mL; 5.58 ± 1.74 lymph nodes dissected had not metastasized; the mean duration of postoperative chest tube drainage was 4.7 ± 1.4 days; and the mean postoperative hospital stay was 6.5 ± 3.0 days. Although 1 patient experienced a prolonged air leak, the other 29 recovered uneventfully. Another patient failed to reach the 2-cm safe margins and subsequently underwent completion lobectomy. CONCLUSIONS: UP-VATS complex segmentectomy is a safe and effective procedure in the treatment of lung cancers, sparing more pulmonary parenchyma and ensuring safe margins, with the disadvantage being the lengthy operative times during early skill acquisition.

PIGF and Flt-1 on the surface of macrophages induces the production of TGF-ß1 by polarized tumor-associated macrophages to promote lung cancer angiogenesis.

BACKGROUND: The interaction between tumor cells and tumor microenvironment is a necessary condition for promoting the metastasis of malignant tumors. METHODS: Two different transwell culture systems were interfered with by recombinant factor placental growth factor (re-PIGF) and the re-PIGF + transforming growth factor-ß1 (TGF-ß1)-neutralizing antibody (anti-TGF-ß1). We performed immunofluorescence, flow cytometry and enzyme linked immunosorbent assay (ELISA) to analyze the expression of PIGF, fms-like tyrosine kinase-1 (Flt-1), macrophage marker F4/80 +, macrophage M2 marker CD163+ and TGF-ß1 in vitro. Meanwhile, cell viability assay and optical microscope assay were conducted to explore the cell viability and vascularization ability of human umbilical vein endothelial cells (HUVECs). RESULTS: Re-PIGF increased the expression of PIGF in A549 cells and the expression of Flt-1 in BM-Mac cells, and significantly enhanced the ability of bone marrow-derived macrophages (BM-Mac) to transform into macrophages. At the same time, re-PIGF increased the expression of cytokine TGF-ß1 in A549 cells/BM-Mac transwell culture system. On the contrary, re-PIGF + anti-TGF-ß1 inhibited the expression of Flt-1 in BM-Mac cells and inhibited the ability of BM-Mac cells to transform into macrophages. Finally, re-PIGF + anti-TGF-ß1 reduced the cell viability and angiogenesis of HUVECs. CONCLUSION: The surface molecule PIGF of lung cancer cells could bind to the receptor Flt-1 on the surface of macrophages, thereby increasing the production of TGF-ß1, and ultimately promoting the formation of angiogenesis in lung cancer.

microRNA-877 contributes to decreased non-small cell lung cancer cell growth via the PI3K/AKT pathway by targeting tartrate resistant acid phosphatase 5 activity.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer death in both men and women. microRNAs (miRs) can exert important functions in cancer development. However, the role of miR-877 in NSCLC as it relates to tartrate resistant acid phosphatase 5 (ACP5) is unknown. For this study, the gain-and-loss-of-function experiments were performed to explore the effects of miR-877 and ACP5 on NSCLC. miR-877 expression in LC and paracancerous tissues, lung epithelial cell line and NSCLC cell lines was detected, and the association between miR-877 expression and clinical features of LC patients was analyzed. The levels of ACP5, epithelial-mesenchymal transition (EMT) markers and apoptosis-related proteins were measured. In vivo experiments were conducted for further validation. Consequently, we found that miR-877 expression was lowered in LC tissues and cell lines, and correlated with clinical stage, differentiation, lymph node metastasis and prognosis of NSCLC patients. Additionally, miR-877 was determined to inhibit ACP5 activity, and miR-877 downregulated the PI3K/AKT pathway by silencing ACP5. Furthermore, overexpression of miR-877 inhibited the viability, migration, invasion and EMT of NSCLC cells, but promoted cell apoptosis. In conclusion, miR-877 overexpression inhibited malignant biological behaviors of NSCLC cells by downregulating ACP5 and inactivating the PI3K/AKT pathway.

Expression of MMP-1/PAR-1 and patterns of invasion in oral squamous cell carcinoma as potential prognostic markers.

BACKGROUND: Matrix metalloproteinase (MMP)-1 degrades type I collagen of the extracellular matrix and also activates protease activated receptor (PAR)-1 to induce angiogenesis. The aims of this study were to evaluate microvessel density (MVD) and the expression of PAR-1 and MMP-1 in oral squamous cell carcinoma (SCC) specimens with different patterns of invasion (POI) and to evaluate their association with clinical outcomes. METHODS: Seventy-four surgically obtained oral SCC samples were classified by POI according to hematoxylin-eosin staining. MVD and the localization and intensity of PAR-1 and MMP-1 expression were detected by immunohistochemistry. RESULTS: Of the 74 oral SCC samples, 18, 5, 34, and 17 showed type I, II, III, and IV POI, respectively. MVD and expression levels of MMP-1 and PAR-1 differed between POI types I-II and POI types III-IV. Patients with low tumor expression of MMP-1 and PAR-1 and low MVD had a longer survival time than those with high tumor expression of MMP-1 and PAR-1. Moreover, the survival time of patients with POI types III-IV was shorter than that of patients with POI types I-II. CONCLUSION: POI combined with expression levels of MMP-1 and PAR-1 may be a valuable tool for assessing the clinical prognosis of patients with oral SCC.