Feasibility research of enhanced recovery after surgery implemented in esophageal cancer patients who underwent neoadjuvant chemotherapy.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a perioperative management protocol to accelerate patient recovery. This study aimed to evaluate the feasibility of ERAS protocols implemented in patients who underwent neoadjuvant chemotherapy (NACT) before minimally invasive McKeown esophagectomy. METHODS: This retrospective study compared the short-term clinical outcomes in esophagectomy patients from June 2018 to June 2021. Subjects were divided into two categories: those who underwent NACT (NACT group) and the non-NACT group. RESULTS: There was no significant difference in total postoperative complication morbidity between the NACT and non-NACT groups (21.2% vs. 20.7%, P=0.936). In addition, the hospital length of stay post-surgery (7.90 vs. 7.71 days, P=0.424) was not significantly longer when compared to the non-NACT group. The time to chest tube removal (5.37 vs. 5.13 days, P=0.238) and first bowel movement (2.92 vs. 3.01 days, P=0.560) was also similar between the two groups. CONCLUSIONS: There was no significant difference in postoperative complications rate, postoperative hospital length of stay, and readmission rate between the two group. This study proved that ERAS protocols seemed to be safe and feasible for patients who received NACT before esophagectomy.

siRNA of DNA polymerase iota inhibits the migration and invasion in the lung cancer cell A549.

DNA polymerase iota (polɩ) is a member of low-fidelity Y-family of DNA polymerases. Our previous studies have demonstrated that the overexpression of polι is associated with the poorer prognosis in lung cancer patients. Here, we designed the small interfering RNA (siRNA) targeting polɩ gene (POLI) to investigate the effect of polɩ on the proliferation, apoptosis, and invasion of the lung cancer cell line A549 in order to reveal the role of polι in lung cancer progression. Our results showed that siRNA of POLI had no significant effect on the proliferation and apoptosis of the lung cancer cell line A549. However, siRNA of POLI could inhibit the migration and invasion of the lung cancer cell line A549 by upregulating the E-cadherin expression and downregulating the expressions of N-cadherin, MMP2, and MMP9. Together, our findings indicate that polι plays a positive role in lung cancer progression via promoting the migration and invasion of lung cancer cells. Therefore, polι might be a potential target for the clinical treatment of lung cancer in the future.

Regulator of G-protein signaling 4: A novel tumor suppressor with prognostic significance in non-small cell lung cancer.

Regulator of G-protein signaling (RGS) family members are regulatory molecules which act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. Emerging data indicated that RGS members were involved with tumorigenesis and metastasis. In the current study, we identified RGS4 as a novel tumor suppressor with prognostic significance in non-small cell lung cancer (NSCLC). To be specific, we found that RGS4 expression was higher in normal lung tissues than NSCLC specimens (P = 0.003). Further studies demonstrated that RGS4 was generally down-regulated in NSCLC specimens compared with the matched normal lung tissues, both at mRNA and protein levels. In addition, correlational analysis indicated that RGS4 expression levels negatively correlated with lymph node metastasis (P = 0.009) and TNM stage (P = 0.008). Survival analysis demonstrated that patients with lower RGS4 protein expression exhibited a much worse 5-year overall survival and 5-year disease-free survival than those with high expression. More importantly, we proved that over-expression of RGS4 in NSCLC cells decreased invasion and migration due to inhibition of MMP2/9 and reversal of EMT while down-regulation of RGS4 in normal lung cell lines promoted invasion and migration. At last, nude mice metastatic model proved that over-expression of RGS4 suppressed tumor metastasis in vivo. All of these results confirmed the critical role of RGS4 in NSCLC progression.

Rotenone induces apoptosis in human lung cancer cells by regulating autophagic flux.

Reactive oxygen species (ROS) are at the center of many physiological and pathological processes. ROS generated due to oxidative stress can potentiate both cancer initiation and progression. Rotenone, which is an inhibitor of the mitochondrial electron transport chain complex I, results in the activation of NOX2 and release of ROS, and has been shown to display anticancer activity through the induction of apoptosis in various cancer cells. The mechanistic link between rotenone-dependent activation of NOX2 and induction of apoptosis is still elusive. In this study, we used the human lung cancer A549 cells to study the molecular mechanism(s) involved between rotenone-dependent activation of NOX2 and impairment of autophagic machinery. We report that acute exposure to rotenone induced mild NOX2-dependnet oxidative stress, which impaired the autophagic flux, resulting in cytosolic accumulation of LC3 and p62/STSQM1. We further show that this induction occurs through the PI3K/Akt/mTORC1 signaling pathway. We furthermore show that chronic exposure to rotenone lead to excessive NOX2-dependent ROS generation, increases autophagy, and decreases p62 level via increased-autophagic flux. Taken together, this study is the first mechanistic elucidation of how rotenone can be used to potently target cancer cells without overhauling the entire cellular machinery. © 2016 IUBMB Life 68(5):388-393, 2016.

Human mesenchymal stem cells with adenovirus-mediated TRAIL gene transduction have antitumor effects on esophageal cancer cell line Eca-109.

The apoptotic ligand TNF-related apoptosis-inducing ligand (TRAIL) is believed to be a promising candidate for cancer gene therapy, yet gene therapy strategies to tackle this disease systemically are often impaired by inefficient delivery of the vector to the tumor tissue. Mesenchymal stem cells (MSCs) have been shown to home to tumor sites and could potentially act as a shield and vehicle for an antitumor gene therapy vector. Here, we used an adenoviral vector expressing TRAIL to transduce MSCs and studied the apoptosis-inducing activity of these TRAIL-carrying MSCs on esophageal cancer cell Eca-109. Our results showed that, in vitro, TRAIL-expressing MSCs were able to inhibit proliferation and induce apoptosis in Eca-109 cells by an MTT assay, co-culture experiments and flow cytometry analysis. In vivo, TRAIL-expressing MSCs also displayed an ability to inhibit tumor growth in an Eca-109 xenograft mouse model. Together, our findings indicated that the gene therapy strategy of MSCs-based TRAIL gene delivery has a wide potential value for improving the treatment of esophageal cancer.

Serum-volatile organic compounds in the diagnostics of esophageal cancer.

The early diagnosis of esophageal cancer (EC) is extremely challenging due to a lack of effective diagnostic methods. The study presented herein aims to assess whether serum volatile organic compounds (VOCs) could be utilised as emerging diagnostic biomarkers for EC. Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect VOCs in the serum samples of 55 patients with EC, with samples from 84 healthy controls (HCs) patients analysed as a comparison. All machine learning analyses were based on data from serum VOCs obtained by GC-IMS. A total of 33 substance peak heights were detected in all patient serum samples. The ROC analysis revealed that four machine learning models were effective in facilitating the diagnosis of EC. In addition, the random forests model for 5 VOCs had an AUC of 0.951, with sensitivities and specificities of 94.1 and 96.0%, respectively.

Down-regulation of MTA1 protein leads to the inhibition of migration, invasion, and angiogenesis of non-small-cell lung cancer cell line.

Metastasis-associated protein 1 (MTA1) high expression has been detected in a wide variety of human aggressive tumors and plays important roles in the malignant biological behaviors such as invasion, metastasis, and angiogenesis. However, the specific roles and mechanisms of MTA1 protein in regulating the malignant behaviors of non-small-cell lung cancer (NSCLC) cells still remain unclear. To elucidate the detailed functions of MTA1 protein, we down-regulated the MTA1 protein expression in NSCLC cell line by RNA interference (RNAi) in vitro, and found that down-regulation of MTA1 protein significantly inhibited the migration and invasion potentials of 95D cells. Further research revealed that down-regulation of MTA1 protein significantly decreased the activity of matrix metalloproteinase-9, which could be the mechanism responsible for the inhibition of 95D cells migration and invasion. In addition, the tube formation assay demonstrated that the number of complete tubes induced by the conditioned medium of MTA1-siRNA 95D cells was significantly smaller than that of 95D cells. These findings demonstrate that MTA1 protein plays important roles in regulating the migration, invasion, and angiogenesis potentials of 95D cells, suggesting that MTA1 protein down-regulation by RNAi might be a novel therapeutic approach to inhibit the progression of NSCLC.

Down-regulation of heparanase leads to the inhibition of invasion and proliferation of A549 cells in vitro and in vivo.

Heparanase is a mammalian endoglycosidase that degrades heparan sulfate at the cell surface and in the extracellular matrix. The expression of heparanase was detected in a wide variety of human malignant tumors and closely associated with tumor invasion, metastasis, and angiogenesis. However, the specific roles of heparanase and its mechanisms of regulating the malignant potential of non-small cell lung cancer (NSCLC) cells still remain unclear. In the present study, the expression of heparanase was down-regulated in NSCLC cell line by antisense oligodeoxynucleotide. Results showed that down-regulation of heparanase led to significant inhibition of invasive and proliferative potentials of A549 cells in vitro and in vivo. Further research demonstrated that down-regulation of heparanase significantly inhibited the angiogenic potential of A549 cells, which might be the mechanism responsible for the inhibition of A549 cell proliferation in BALB/c nude mice in vivo. These findings demonstrate that heparanase plays essential roles in regulating the invasion, proliferation, and angiogenesis of A549 cells.

Identification of urinary volatile organic compounds as a potential non-invasive biomarker for esophageal cancer.

Early diagnosis of esophageal cancer (EC) is extremely challenging. The study presented herein aimed to assess whether urinary volatile organic compounds (VOCs) may be emerging diagnostic biomarkers for EC. Urine samples were collected from EC patients and healthy controls (HCs). Gas chromatography-ion mobility spectrometry (GC-IMS) was next utilised for volatile organic compound detection and predictive models were constructed using machine learning algorithms. ROC curve analysis indicated that an 8-VOCs based machine learning model could aid the diagnosis of EC, with the Random Forests having a maximum AUC of 0.874 and sensitivities and specificities of 84.2% and 90.6%, respectively. Urine VOC analysis aids in the diagnosis of EC.

Metastasis-associated protein 1 nuclear expression is closely associated with tumor progression and angiogenesis in patients with esophageal squamous cell cancer.

BACKGROUND: The purposes of the present study were to detect the expression of metastasis-associated protein 1 (MTA1) in patients with esophageal squamous cell cancer (ESCC), and to evaluate the relevance of MTA1 protein expression to the tumor progression, angiogenesis, and prognosis. METHODS: Both MTA1 protein and intratumoral microvessels were examined by immunohistochemical staining in 131 ESCC patients who successfully underwent subtotal esophagectomy and esophagogastric anastomosis at Qilu Hospital between Jan 2004 and Dec 2005. Intratumoral microvessel density (MVD) was recorded by counting CD-34 positive immunostained endothelial cells. All statistical analyses were performed with SPSS 13.0 statistical software. RESULTS: High expression of MTA1 protein was detected in 57 cases and significantly correlated with tumor invasion depth (P = 0.041), lymph node metastasis (P = 0.021), pathologic stage (P = 0.003), and MVD (P = 0.044). Survival analysis showed that patients with MTA1 protein high expression had significantly poor overall 5-year survival (P = 0.002), and the factor found on multivariate analysis to significantly affect overall survival was only pathologic stage (P = 0.040). Further stratified survival analysis split by pathologic stage demonstrated that MTA1 protein high expression significantly predicted unfavorable prognosis among patients with pathologic stage II disease (P = 0.006). CONCLUSIONS: High expression of the MTA1 protein is common in ESCC, and is closely associated with tumor progression, increased tumor angiogenesis, and poor survival. These findings indicate that MTA1 protein has clinical potentials as a useful indicator of progressive phenotype, a promising prognostic predictor to identify patients with poor prognosis, and a potential novel therapeutic target of antiangiogenesis for patients with ESCC.

Diallyl trisulfide induces apoptosis and inhibits proliferation of A549 cells in vitro and in vivo.

Lung cancer is the leading cause of cancer-related mortality all over the world. In recent years, pulmonary adenocarcinoma has surpassed squamous cell carcinoma in frequency and is the predominant form of lung cancer in many countries. Epidemiological investigations have shown an inverse relationship between garlic (Allium sativum) consumption and death rate from many cancers. Diallyl trisulfide (DATS) is one of the garlic-derived compounds (also known as: organosulfer compounds, OSC). DATS can induce apoptosis and inhibit the growth of many cancer cell lines. Our study demonstrated that the apoptotic incidents induced by DATS were a mitochondria-dependent caspase cascade through a significant decrease of the anti-apoptotic Bcl-2 that resulted in up-regulation of the ratio of Bax/Bcl-2 and the activity of caspase-3, -8, and -9. Eventually, DATS induced the apoptosis and inhibited the proliferation in a concentration- and time-dependent manner. Furthermore, by establishing an animal model of female BALB/c nude mice with A549 xenografts, we found that oral gavage of DATS significantly retarded growth of A549 xenografts in nude mice without causing weight loss or any other side effects compared with the control group. All the evidence both in vitro and in vivo suggested that DATS could be an ideal anti-cancer drug.

Reducing ammonia emissions from laying-hen houses through dietary manipulation.

Feed additives can change the microbiological environment of the animal digestive track, nutrient composition of feces, and its gaseous emissions. This 2-yr field study involving commercial laying-hen houses in central Iowa was conducted to assess the effects of feeding diets containing EcoCal and corn-dried distillers grain with solubles (DDGS) on ammonia (NH3), hydrogen sulfide (H2S), and greenhouse gas (CO2, CH4, and N2O) emissions. Three high-rise layer houses (256,600 W-36 hens per house) received standard industry diet (Control), a diet containing 7% EcoCal (EcoCal) or a diet containing 10% DDGS (DDGS). Gaseous emissions were continuously monitored during the period of December 2007 to December 2009, covering the full production cycle. The 24-month test results revealed that mean NH3 emission rates were 0.58 +/- 0.05, 0.82 +/- 0.04, and 0.96 +/- 0.05 g/hen/day for the EcoCal, DDGS, and Control diet, respectively. Namely, compared to the Control diet, the EcoCal and DDGS diets reduced NH3 emission by an average of 39.2% and 14.3%, respectively. The concurrent H2S emission rates were 5.39 +/- 0.46, 1.91 +/- 0.13, and 1.79 +/- 0.16 mg/ hen/day for the EcoCal, DDGS, and Control diet, respectively. CO2 emission rates were similar for the three diets, 87.3 +/- 1.37, 87.4 +/- 1.26, and 89.6 +/- 1.6 g/hen/day for EcoCal, DDGS, and Control, respectively (P = 0.45). The DDGS and EcoCal houses tended to emit less CH4 than the Control house (0.16 and 0.12 vs. 0.20 g/hen/day) during the monitored summer season. The efficacy of NH3 emission reduction by the EcoCal diet decreased with increasing outside temperature, varying from 72.2% in February 2009 to -7.10% in September 2008. Manure of the EcoCal diet contained 68% higher ammonia nitrogen (NH3-N) and 4.7 times higher sulfur content than that of the Control diet. Manure pH values were 8.0, 8.9, and 9.3 for EcoCal, DDGS, and Control diets, respectively. This extensive field study verifies that dietary manipulation provides a viable means to reduce NH3 emissions from modern laying-hen houses.

Enhanced Recovery After Surgery Improves Short-term Outcomes in Patients Undergoing Esophagectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a perioperative management protocol used to accelerate patient recovery. This study evaluated its benefits in patients with resectable esophageal cancer. METHODS: This retrospective study compared patients before (January 2013 to December 2016) and after (June 2018 to December 2020) ERAS protocol implementation in our hospital. A propensity score-matched analysis was used to compare short-term surgical outcomes between ERAS and non-ERAS groups. After propensity score matching each group included 243 patients. RESULTS: There were significant differences in hospital length of stay after surgery (7.40 vs 11.17 days, P < .001) and hospitalization cost (¥69380 vs ¥78075, P < .001) between the ERAS and non-ERAS groups. The time to chest tube removal (4.91 vs 7.16 days, P < .001) and first bowel movement (2.87 vs 3.97 days, P < .001) was significantly shorter in the ERAS group. However there was no significant difference in total postoperative complication morbidity (20.2% vs 25.1%, P = .193). The complication of postoperative atelectasis or pneumonia was significantly lower in the ERAS group (P = .003), but there was no significant difference in occurrence of at least grade III complications between the 2 groups (12.3% vs 11.5%, P = .889). CONCLUSIONS: We demonstrated that ERAS could reduce hospital stay, numerical pain scores, and hospitalization costs without increasing postoperative complication and readmission. Furthermore subgroup analyses revealed that ERAS was safe for older people (>70 years old).

Human mesenchymal stem cells play a dual role on tumor cell growth in vitro and in vivo.

Nowadays, some evidences demonstrate that human mesenchymal stem cells (hMSCs) favor tumor growth; however, others show that hMSCs can suppress tumorigenesis and tumor growth. With the indeterminateness of the effect of hMSCs on tumors, we investigated the effect of hMSCs on lung cancer cell line A549 and esophageal cancer cell line Eca-109 in vitro and in vivo. Our results revealed that hMSCs inhibited the proliferation and invasion of A549 and Eca-109 cells, arrested tumor cells in the G1 phase of the cell cycle and induced the apoptosis of tumor cells in vitro by using a co-culture system and the hMSCs-conditioned medium. However, animal study showed that hMSCs enhanced tumor formation and growth in vivo. Western blotting and immunoprecipitation data showed that the expressions of proliferating cell nuclear antigen (PCNA), Cyclin E, phospho-retinoblastoma protein (pRb), B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL, and matrix metalloproteinase 2 (MMP-2) were downregulated and the formation of Cyclin E-cyclin-dependent kinase 2 (CDK2) complexes was inhibited in the tumor cells treated with the hMSCs-conditioned medium. According to the observation of tumor mass and the result of microvessel density (MVD), we found that the promoting role of hMSCs on tumor growth was related with the increase of tumor vessel formation. Our present study suggests that hMSCs have a contradictory effect on tumor cell growth between in vitro and in vivo, and therefore, the exploitation of hMSCs in new therapeutic strategies should be cautious under the malignant conditions.

Overexpression of metastasis-associated protein 1 is significantly correlated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer.

BACKGROUND: The aims of this work are to detect the expression levels of metastasis-associated protein 1 (MTA1) in patients with early-stage non-small cell lung cancer (NSCLC), and to investigate the relationship of MTA1 protein with clinicopathologic factors, tumor angiogenesis, and prognosis. METHODS: One hundred and two patients with pathologic stage I NSCLC who successfully underwent curative surgical resection were enrolled in this study. Immunohistochemical staining for MTA1 and CD34 was performed using the streptavidin-peroxidase method, and intratumoral microvessel density (MVD) was recorded by counting CD34-positive immunostained endothelial cells. All statistical analyses were performed with SPSS statistical software to determine the effects of MTA1 protein on clinicopathologic factors, tumor angiogenesis, and prognosis. RESULTS: MTA1 protein overexpression was detected in 41 cases and was significantly associated with MVD (P = 0.008). MTA1 protein overexpression and high MVD were significantly associated with tumor relapse (P = 0.004 and 0.007) and poor 5-year disease-free survival (P = 0.001 and 0.004). Patients with MTA1 protein overexpression and high MVD had significantly poor overall survival (P = 0.005 and 0.043) and disease-specific survival (P = 0.006 and 0.031) at 5 years after operation. Multivariate analysis demonstrated that MTA1 protein overexpression was an independent prognosticator for unfavorable disease-free, overall, and disease-specific survival (P = 0.011, 0.024, and 0.046). CONCLUSIONS: MTA1 protein overexpression is common in early-stage NSCLC and is significantly associated with tumor angiogenesis and poor survival. These findings suggest that MTA1 may have clinical potential as a promising predictor to identify individuals with poor prognostic potential and as a possible novel target molecule of antiangiogenic therapy for patients with early-stage NSCLC.

Inhibition of lung cancer cell proliferation mediated by human mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs) are mostly studied for their potential clinical use. Recently, much attention in the field of cancer research has been paid to hMSCs. In this study, we investigated the influence of hMSCs on the proliferation of lung cancer cell lines SK-MES-1 and A549 in vitro and in vivo by using a co-culture system and the hMSCs-conditioned medium. Our results demonstrated that hMSCs could inhibit the proliferation of SK-MES-1 and A549 cells, and induce the apoptosis of tumor cells in vitro via some soluble factors. Animal study showed that these soluble factors from hMSCs could suppress tumorigenesis and tumor angiogenesis by treating preliminarily tumor cells with the hMSCs-conditioned medium. The downregulated expression of vascular endothelial growth factor in tumor cells might be the mechanism of interference in tumor angiogenesis, which was verified by western blot analysis and immunohistochemistry assay. Taken together, our results suggested that the hMSCs could inhibit tumor cell growth by secreting some soluble factors.

Identification of key genes associated with esophageal adenocarcinoma based on bioinformatics analysis.

BACKGROUND: Esophageal adenocarcinoma (EAC) is an aggressive malignancy and accounts for the majority of cancer-related death worldwide. It is often diagnosed at an advanced stage and entails a poor prognosis for those afflicted. The mechanisms of its pathogenesis and progress remain unclear and require urgent elucidation. This study aimed to identify specific genes and potential pathways associated with the progression and prognosis of EAC using bioinformatics analyses. METHODS: EAC microarray datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were analyzed to identify differentially expressed genes (DEGs) using bioinformatics analysis. The DEGs in TCGA were then analyzed to construct a co-expression network by weighted correlation network analysis (WGCNA), and module-clinical trait relationships were analyzed to explore the genes that associated with clinicopathological parameters of EAC. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were performed for the cancer-related genes, and a DEG-based protein-protein interaction (PPI) network was used to extract hub genes through Cytoscape plugins. The consensus survival analysis for EAC (OSeac) was performed to identify the prognosis-related genes. The immune infiltration was evaluated by tumor immune estimation resource (TIMER) algorithms, and a risk score prognostic model was established using univariate, multivariate Cox proportional hazards regression, and lasso regression analysis. RESULTS: Ultimately, 190 cancer-related DEGs were identified, 6 of which were found to play vital roles in the progression of EAC, including ACTA2, BGN, CALD1, COL1A1, COL4A1, and DCN. The risk score prognostic model consisted of 6 other genes that had an important impact on the prognosis of EAC, including CLDN3, EPB41L4A, ESM1, MT1X, PAQR5, and PLAU. The area under the curve of the prognostic model for predicting the survival of patients at 1, 2, and 3 years was 0.707, 0.702, and 0.726, respectively. CONCLUSIONS: This study identified several genes with the potential to become useful targets for the diagnosis and treatment of EAC. The 6-gene-related risk score prognostic model and nomogram based on these genes may be a reliable tool for predicting the prognosis of patients with EAC.

MiR-522-3p inhibits proliferation and activation by regulating the expression of SLC31A1 in T cells.

We investigated the role of miR-522-3p in thymoma-associated myasthenia gravis (TAMG), and the mechanism of action in T cells. The miR-522-3p expression in normal serum, non-thymoma MG patient serum and TAMG patient serum and tissues was detected by quantitative real-time PCR (qRT-PCR), respectively. We assessed miR-522-3p expression in Jurkat cells and human CD4+ T cells after activation by anti-CD3 and anti-CD28 using qRT-PCR. The viability, proliferation, cycle distribution and the levels of CD25, CD69, interleukin-2 (IL-2) and IL-10 in transfected Jurkat cells were detected by Cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, qRT-PCR, respectively. Targeting relationships of miR-522-3p and SLC31A1 were predicted and validated by bioinformatics analysis and dual-luciferase reporter. The viability, proliferation, cycle distribution and the levels of SLC31A1, CD25, CD69, IL-2 and IL-10 in transfected Jurkat cells were detected by above methods and western blot. The miR-522-3p expression was declined in TAMG and activated T cells. MiR-522-3p inhibitor promoted cell viability, EdU positive cells, cycle progression, and the level of CD25, CD69, IL-2 and IL-10 in Jurkat cells, while the effect of miR-522-3p mimic was the opposite. SLC31A1 was targeted by miR-522-3p, and miR-522-3p inhibited SLC31A1 expression. Overexpressed SLC31A1 reversed the inhibitory effects of miR-522-3p mimic on cell viability, EdU positive cell, cycle progression, and the levels of IL-2 and IL-10 in transfected Jurkat cells. MiR-522-3p expression was down-regulated in TAMG, and miR-522-3p inhibited proliferation and activation by regulating SLC31A1 expression in T cells.

Circular RNA hsa-circ-000881 suppresses the progression of lung adenocarcinoma in vitro via a miR-665/PRICKLE2 axis.

BACKGROUND: Circular RNA (circRNA) has become a new focus in the field of tumor biology research in recent years. Many circRNAs have been showed to play an important role in the progression of lung adenocarcinoma (LUAD). In this work, we studied the oncological role of hsa-circ-000881 in LUAD and attempted to explore the related mechanism. METHODS: The relative expressions of hsa-circ-000881, miR-665, and PRICKLE2 were detected by RT-qPCR or western blot. Functional assays were conducted to analyze the role of hsa-circ-000881 in the proliferation, migration, and invasion of LUAD cells. A luciferase reporter assay was performed to verify whether hsa-circ-000881, miR-665, and PRICKLE2 interact with each other. RESULTS: Circ-000881 was remarkably downregulated in LUAD. Overexpression of circ-000881 attenuated cell growth, migration, and invasion, whereas its knockdown enhanced the malignancy of LUAD cells. The results of luciferase reporter assay and bioinformatics analysis confirmed that circ-000881 served as a sponge for miR-665, and PRICKLE2 was a direct target of miR-665.Overexpression of miR-665 or silencing of PRICKLE2 abolished circ-000881-mediated inhibition of malignant tumor behavior in LUAD cells. CONCLUSIONS: Circ-000881 has inhibitory effects on LUAD via a miR-665/PRICKLE2 axis, suggesting that circ-000881 may be an underlying therapeutic target for LUAD.

ZHX2 inhibits proliferation and promotes apoptosis of human lung cancer cells through targeting p38MAPK pathway.

OBJECTIVE: To investigate the effect of ZHX2 on lung cancer cells proliferation and apoptosis. MATERIALS AND METHODS: The mRNA and protein expression of ZHX2 were detected by qRT-PCR and western blot, respectively. The human lung cancer cells were divided into Control, NC, ZHX2, SB, and ZHX2 + Ani groups. The cell proliferation was detected by CCK-8 assay and the cell migration and invasion were detected by Transwell assay. Cell apoptosis was detected by flow cytometry. Apoptosis and p38MAPK signaling pathway related proteins were detected by western blot. The nude mice model of lung cancer xenograft was constructed. The tumor volume and tumor weight were measured. The expression of PCNA protein in tumor tissues was detected by immunohistochemistry. The apoptosis of tumor cells was detected by TUNEL staining. The ZHX2 and p38MAPK signaling pathway related proteins in tumor tissues were detected by western blot. RESULTS: The expression of ZHX2 gene and protein in the cancer cell lines were significantly decreased. Compared with control and NC groups, the cells proliferation, migration and invasion were inhibited in ZHX2 and SB groups, while the apoptosis and apoptosis related proteins were increased (p< 0.05). Meanwhile, compared with ZHX2 group, the tumor growth rate, volume, weight, the percentage of PCNA-positive cells, and p-P38 MAPK/P38 MAPK were increased significantly in ZHX2 + Ani group, while the apoptotic index and the expression of MMP-9 protein were significantly decreased (p< 0.05). CONCLUSION: ZHX2 could inhibit proliferation and promote apoptosis of lung cancer cells by inhibiting p38MAPK signaling pathway.