Kazakh adults in Xinjiang have a prevalent obesity problem but a low prevalence of diabetes.

BACKGROUND: The prevalence of diabetes and obesity has been continuously rising worldwide over the last three decades, particularly in China. The prevalence varies widely among different ethnicities. In this study, we investigated the prevalence of diabetes and obesity, as well as the associated factors for diabetes in Kazakh adults in Xinjiang to improve diabetes screening. METHODS: We collected data from the Xinjiang physical examination in 2018, including a total sample of 118,505 Kazakh adults in Altay District. Data on demographic characteristics, medical history, physical examination, fasting plasma glucose (FPG) and serum lipid profiles were collected. The chi-square test was used to examine the differences between multiple variables. Multivariate logistic regression was performed to identify the factors associated with diabetes. RESULTS: The mean age was 43. 66 years (SD 14.14). 49.3% of the population were women and 75.5% were rural residents. The mean FPG was 5.33 mmol/L (SD 1.22). The prevalence of diabetes was 6.3% and 4.1% received a new diagnosis by FPG. 26.6% were diagnosed with impaired fasting glucose (IFG). The mean body mass index (BMI) was 26.29 kg/m2 (SD 14.14) and the mean waist circumference was 87.69 cm (SD 12.74). 33.2% of the population were overweight, and 33.0% were obese. The prevalence of central obesity was 51.4%. Diabetes was mostly positively associated with hypertension (OR = 3.821, P<0.001), hypertriglyceridemia (OR = 2.757, P<0.001), and hyper-LDL-cholesterolemia (OR = 2.331, P<0.001) in the Kazakh population. The ORs for overweight, obesity and central obesity predictive of diabetes were 1.265, 1.453 and 1.222 ( all P<0.001), respectively. CONCLUSIONS: Despite having a high prevalence of obesity and central obesity, the Kazakh population had a considerably low prevalence of diabetes. Obesity was not the most important risk factor for diabetes in Kazakh individuals. The awareness of diabetes was low. When screening for diabetes in Kazakhs, those with hypertension or dyslipidemia should receive more attention.

Bifunctional Lanthanide-Based Coordination Polymers: Conversion of CO2 and Highly Selective Luminescence Sensing for Acetylacetone.

A series of bifunctional Ln(III)-based coordination polymers (CPs) {Ln(L)(DMA)2(NO3)}n [Ln(III) = Eu (1), Gd (2), and Dy (3); organic ligand H2L = 2,2'-(1,3,5,7-tetrahydroxyoctahydro-4,8-ethanopyrrolo[3,4-f]isoindole-2,6(1H,3H)-diyl)diacetic acid)] have been successfully synthesized. CPs 1-3 are isostructural and constructed from the dimeric Ln2 unit in which two adjacent LnIII ions are bridged by two µ3-carboxyl oxygens, and the Ln2 dimeric unit is connected by two NO3- ions, four DMA molecules, and four completely protonated L2- ligands forming a 2D layer structure. The magnetic research reveals that CP 2 shows a significant cryogenic magnetocaloric effect (-ΔSm = 22.9 J kg-1 K-1; T = 2.0 K and ΔH = 7.0 T), whereas CP 3 exhibits slow magnetic relaxation property under Hdc = 0 Oe field. Additionally, the luminescence explorations revealed that CP 1 can act as a recyclable luminescent probe for pollutant acetylacetone among various small organic solvent molecules, and the corresponding detection limit is 10-7 mol/L. More importantly, CP 1 also exhibits good catalytic performance in the cycloaddition reaction of CO2 and epoxides or cyanamides under mild conditions. As far as we know, CP 1 represents the first bifunctional lanthanide homogeneous catalyst that can efficiently catalyze the reaction of cyanamides/epoxides with CO2 simultaneously.

Long non-coding RNA DSCAS regulates cisplatin sensitivity in lung squamous cell carcinoma by competitively binding to miR-646-3p.

Background: Platinum-based chemotherapy is the main treatment for advanced lung squamous cell carcinoma (LUSC). Eventually, patients with LUSC develop resistance to cisplatin, which affects the prognosis. Hence, the researchers sought to find a lncRNA in LUSC that affects resistance to cisplatin. Methods: The lncRNA microarray assay was used to screen the differential expression of lncRNA. qPCR was used to detect lncRNA DSCAS (DSCAS) expression in tissues and cell lines. Lentiviral transfection was used to regulate the expression of DSCAS. CCK-8, colony formation, wound healing, transwell, and flow cytometry assays were used to assess the biological behaviors and sensitivity to cisplatin of LUSC cell. RNA-RNA interaction was tested using the dual luciferase reporting assay, RNA-IP, and RNA-RNA pull-down assay. The downstream pathway of DSCAS was verified by qPCR and Western blotting assays. Results: DSCAS was highly expressed in LUSC tissues and cells, and its expression levels were higher in cisplatin-insensitive tissues than in cisplatin-sensitive tissues. Elevation of DSCAS promoted cell proliferation, migration and invasion as well as increased cisplatin resistance of lung cancer cells, while demotion of DSCAS inhibited cell proliferation, migration and invasion as well as decreased the cisplatin resistance of lung cancer cells. DSCAS bound to miR-646-3p to regulate the expression of Bcl-2 and Survivin, which affected the cell apoptosis and sensitivity to cisplatin in LUSC cells. Conclusions: DSCAS regulates biological behavior and cisplatin sensitivity in LUSC cells by competitively binding to miR-646-3p to mediate the expression of Survivin and Bcl-2, known as apoptosis-related proteins.

[Retracted] Overexpression of miR­203 increases the sensitivity of NSCLC A549/H460 cell lines to cisplatin by targeting Dickkopf­1.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the mouse images shown in Fig. 5A and the flow cytometric assay data shown in Fig. 4A and B were strikingly similar to data appearing in different form in other articles written by some of the same authors, but which had already been published elsewhere or were already under consideration for publication, prior to this paper's submission to Oncology Reports. In view of the fact that these apparent duplications of data have come to light, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 37: 2129­2136, 2017; 10.3892/or.2017.5505].

Efficacy Differences of First-line EGFR-TKIs Alone vs in Combination with Chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alterations.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are often associated with non-EGFR genetic alterations, which may be a reason for the poor efficacy of EGFR tyrosine kinase inhibitors (TKIs). Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations. METHODS: Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant non-EGFR genetic alterations were retrospectively collected. And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy. Demographic, clinical and pathological data were collected, and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression. Survival data were obtained through face-to-face or telephone follow-up. The differences between the two groups in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS: 107 patients were included, including 63 cases in the combination group and 44 cases in the monotherapy group. The ORR were 78% and 50% (P=0.003), and DCR were 97% and 77% (P=0.002), respectively. At a median follow-up of 13.7 mon, a PFS event occurred in 38.1% and 81.8% of patients in the two groups, with median PFS of 18.8 mon and 5.3 mon, respectively (P<0.000,1). Median OS was unreached in the combination group, and 27.8 mon in the monotherapy group (P=0.31). According to the Cox multivariate regression analysis, combination therapy was an independent prognostic factor of PFS CONCLUSIONS: In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations, combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy, which should be the preferred treatment option.

Effect of highly efficient substrate modifier, super-absorbent polymer, on the performance of the green roof.

Green roofs are commonly used in sponge city construction. However, the limitations of substrate thickness and strong sunlight have caused water retention to become the primary problem in the promotion of this technology. Super-absorbent polymer (SAP) is a material with excellent water absorption capacity that is expected to improve the substrate to solve the problem of the insufficient water storage capacity of green roofs. In this study, the basic performances of two types of SAPs, namely polyacrylate sylvite and acrylic acid-attapulgite hybrid (P-SAP and A-SAP, respectively), were evaluated on a bench-scale. The results showed that both SAPs had good water absorption, reusability, and fertilizer protection ability. These SAPs could maintain high water absorption within a certain range of salinity, pH, and temperature. Although water absorption of P-SAP was higher than that of A-SAP, the latter showed a significant advantage in substrate modification. After adding A-SAP (application rate: 0.6%, particle size: 12 mesh), the water storage capacity of the substrate was significantly improved, with an increase in the saturation moisture content of 23.8% and a decrease in the infiltration rate of 48.5%. A simulator of green roof was constructed with A-SAP under optimal conditions. The enhancement of the water retention capacity increased the drought resistance of the plants, which improved their growth; in particular, the fresh weight was 98% higher than that of the control group. A-SAP increased the rate of building up the lawn by 25%. The average soil moisture of the A-SAP group was 63.3%, which was 10.0% higher than that of the control group. An increase of more than 26% in the runoff control capacity was found in the green roof with A-SAP. Overall, our study indicates that A-SAP is a practical and efficient modifier for green roofs.

LncRNA SENCR promotes cell proliferation and progression in non-small-cell lung cancer cells via sponging miR-1-3p.

ABBREVIATION: NSCLC: Non-small cell lung cancer.

Hsa_circ_0010235 functions as an oncogenic drive in non-small cell lung cancer by modulating miR-433-3p/TIPRL axis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a threat to human health. Circular RNAs (circRNAs) have been proved to function in NSCLC development. In this study, the role of circRNA hsa_circ_0010235 in NSCLC progression and the possible molecular mechanism were explored. METHODS: Expression of hsa_circ_0010235, miRNA (miR)-433-3p and TOR signaling pathway regulator-like (TIPRL) was examined by quantitative real-time PCR (qRT-PCR). Cell viability and clonogenicity were detected by cell counting kit-8 (CCK-8) assay and colony formation assay, respectively. Flow cytometry was performed to monitor cell apoptosis and cell cycle distribution. Western blot assay was employed to evaluate the protein levels of TIPRL, light chain 3 (LC3)-II/I and p62. Cell metastasis was assessed by Transwell and wound healing assays. The targeted relationship between miR-433-3p and hsa_circ_0010235 or TIPRL was confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Furthermore, the role of hsa_circ_0010235 in vivo was investigated by xenograft assay. RESULTS: Hsa_circ_0010235 and TIPRL were highly expressed in NSCLC tissues and cells, while miR-433-3p was downregulated. Depletion of hsa_circ_0010235 or gain of miR-433-3p repressed proliferation and autophagy but promoted apoptosis in NSCLC cells. Hsa_circ_0010235 sponged miR-433-3p to upregulate TIPRL expression, so as to affect NSCLC development. Hsa_circ_0010235 knockdown also blocked tumor growth in vivo. CONCLUSION: Hsa_circ_0010235 knockdown suppressed NSCLC progression by regulating miR-433-3p/TIPRL axis, affording a novel mechanism of NSCLC progression.

Mutational Landscape and Evolutionary Pattern of Liver and Brain Metastasis in Lung Adenocarcinoma.

INTRODUCTION: A comprehensive genomic analysis of paired primary tumors and their metastatic lesions may provide new insights into the biology of metastatic processes and therefore guide the development of novel strategies for intervention. To date, our knowledge of the genetic divergence and phylogenetic relationships among diverse metastatic lesions from cancer remains limited. METHODS: We performed whole-exome sequencing in 84 tissue and blood samples from 26 patients with lung adenocarcinoma having liver metastases (LiM) or brain metastases (BrM) before any systemic therapy, with the goal to molecularly characterize the metastatic process. Mutational landscape and evolutionary patterns were compared between paired primary lesions (primary lesion of LiM or BrM) and metastases (metastatic site of LiM or BrM). RESULTS: We found that common driver mutations, including TP53 and EGFR, were highly consistent between paired primary and metastatic tumors. Although tumor mutational burden was comparable among groups, the LiM group had significantly higher mutational and copy number variational similarity than the BrM group between paired primary lesions and metastases (p = 0.019 and p = 0.035, respectively). Phylogenetic analysis further revealed that LiM-competent disseminations had a higher level of genetic similarity to their paired primary lesions and were genetically diverged from their primary tumors at a relatively later stage than those of BrM. These results suggest that LiM favorably followed the linear progression model, whereas BrM was more consistent with the parallel progression model. CONCLUSIONS: This study suggests that the mutational landscape and evolutionary pattern was distinctly different between the LiM and BrM of lung adenocarcinoma.

SNHG11 contributes to NSCLC cell growth and migration by targeting miR-485-5p/BSG axis.

Accumulating studies implied that long noncoding RNAs (lncRNAs) act as essential factors in regulating diverse biological behaviors of cancers. Small nucleolar RNA host gene 11 (SNHG11) has been reported as for its oncogenic properties in several cancer types. However, it is unclear whether SNHG11 exerts functions in non-small cell lung cancer (NSCLC) remains unclear. The aim of this study was to inspect the role and regulatory mechanism of SNHG11 in NSCLC. The expression of SNHG11 in NSCLC cells was analyzed by qRT-PCR. Functional experiments were carried out to determine the effects of SNHG11 silence on the biological behaviors of NSCLC cells, including growth, migration and epithelial-mesenchymal transition. The inhibition of above functions was observed after SNHG11 was silenced. Subcellular fractionation and FISH assays were performed to detect the cellular distribution of SNHG11. Moreover, SNHG11 was found to be a sponge of miR-485-5p that could directly target to Basigin (BSG) mRNA. The interaction between SNHG11 and miR-485-5p as well as between miR-485-5p and BSG was proven by RNA pull down and luciferase reporter assays. Restoration assay confirmed the involvement of miR-485-5p and BSG in SNHG11-mediated NSCLC cellular functions. Conclusively, SNHG11 was overexpressed in NSCLC and functioned as a miR-485-5p sponge to up-regulate BSG.

Heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer.

BACKGROUND: Personalized cancer vaccines based on tumor-derived neoantigens have shown strong and long-lasting antitumor effect in patients with some solid tumors. However, whether neoantigens identified from primary lesions could represent their metastatic lesions, and consequently the effect of vaccine therapy remained unknown. METHODS: To investigate whether neoantigens identified from primary tumors are similar to their matched metastases in lung cancer, we identified 79 samples from 24 cases. All of samples were collected before any systemic therapy. Major criteria for neoantigen identification included: derived from tumor-specific mutations, fold change >10 comparing to germline expression level, high predicted human leukocyte antigen (HLA) binding affinity and peptide of 9-11 amino acids in length. RESULTS: We found a wide range of tumor neoantigen burden in both primaries and metastases. The counts, overall distribution pattern and predicted HLA binding affinity of neoantigens were similar between primaries and metastases. However, only 20% of shared neoantigens (presented in both primaries and metastases) was observed, which were mainly derived from single nucleotide variants (SNVs) and fusions. A variety of corresponding HLA alleles were observed and 50.0% of cases were HLA-C*06:02. Finally, we observed the neoantigen intrametastases homogeneity in patients with sole brain metastases. CONCLUSIONS: Neoantigen landscape in terms of the number, type and predicted HLA binding affinity was similar between primaries and metastases, but the percentage of shared neoantigens is only modest, suggesting vaccine development based solely on primary tumor neoantigen may not offer optimal therapeutic outcome, and shared neoantigen needs to be seriously considered.

Comparable outcomes of nivolumab in patients with advanced NSCLC presenting with or without brain metastases: a retrospective cohort study.

OBJECTIVE: This study aimed to determine whether there is a difference in the efficacy of nivolumab in patients with advanced non-small cell lung cancer (NSCLC) presenting with or without brain metastases. MATERIALS AND METHODS: Patients with advanced NSCLC treated with nivolumab monotherapy were retrospectively analyzed. They were divided into two cohorts according to the presence or absence of brain metastases. The differences between the two cohorts in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR) and overall survival (OS) were investigated, and the intracranial efficacy, including intracerebral objective response rate (IORR), intracranial disease control rate (IDCR) and intracranial progression-free survival (iPFS), were examined in the brain metastasis (BM) cohort. RESULTS: Seventy-three patients (32 with brain metastases and 41 without) were included. The ORRs of the BM cohort and the non-brain metastasis (non-BM) cohort were 25.0% and 19.5% (p = 0.574), DCRs were 53.1% and 56.1% (p = 0.800), respectively. Their median PFS were 2.8 and 4.9 months (p = 0.204), median DORs were 9.8 and 28.8 months (p = 0.003), and median OS were 14.8 and 20.2 months (p = 0.114), respectively. According to the Cox multivariate regression analysis, BM was not an independent prognostic factor. The IORR and IDCR of the BM cohort were 28.1% and 46.9%, respectively, with a median iPFS of 2.2 months. CONCLUSIONS: The efficacy of nivolumab is comparable in patients with NSCLC presenting with and without brain metastases, but the results must be verified in large-scale prospective studies.

CASC15 contributes to proliferation and invasion through regulating miR-766-5p/ KLK12 axis in lung cancer.

Long non-coding RNAs (lncRNAs) are key mediators of cancer. The dysregulation of a lncRNA, CASC15, has been linked to several cancers, except lung cancer. Here, the aim of the study was to explore the role and mechanism of CASC15 in lung cancer regulation, with the focus on its interaction with a potential target, microRNA-766-5p (miR-766-5p) and an oncogene, kallikrein-related peptidase 12 (KLK12). Quantitative real-time PCR (qRT-PCR) was used to assess levels of CASC15, miR-766-5p and KLK12 in lung cancer tissues or cells. Western blot analysis was used to detect KLK12 protein expression. Ectopic expression of CASC15 was induced by a lentiviral system. CCK-8 and transwell assays were used to evaluate lung cancer cell proliferation and invasion, respectively. The interaction among CASC15, miR-766-5p and KLK12 was investigated by bioinformatical analysis and luciferase assay. In lung cancer tissue and cells, CASC15 was upregulated, while miR-766-5p was downregulated. Overexpression of CASC15 promoted lung cancer cell proliferation and invasion. A negative correlation was found between CASC15 and miR-766-5p levels. Overexpression of miR-766-6p reversed the cancer-promoting role of CASC15 in lung cancer cells, which was mediated by KLK12. The tumor-promoting role of CASC15 and tumor-suppressing role of miR-766-5p were also validated in vivo in tumor bearing mice, and KLK12 was also shown as an important mediator. CASC15 promotes lung cancer through the miR-766-5p/KLK12 axis, indicating that CASC15 is a potential therapeutic in lung cancer.

MicroRNA-206 promotes lipopolysaccharide-induced inflammation injury via regulation of IRAK1 in MRC-5 cells.

BACKGROUND: MicroRNAs (miRNAs) have been reported to play crucial role in the airway inflammatory diseases. However, the involvement of miR-206 in airway inflammatory diseases is still uninvestigated. The study aimed to explore the effect of miR-206 on lipopolysaccharide (LPS)-induced inflammation injury in MRC-5 cells, and point out a potential relevance for chronic obstructive pulmonary disease (COPD). METHODS: LPS was utilized to expose MRC-5 cells, then cell viability, cell migration, apoptosis, apoptosis-associated factors, as well as the concentrations and protein levels of IL-6 and IL-8 were explored. After transfected with miR-206 mimic and inhibitor, above parameters were reassessed in LPS-injured cells. Expression level of IRAK1 was examined in miR-206 mimic/inhibitor transfected cells by using RT-qPCR. The effect of IRAK1 on LPS-induced inflammation injury was investigated in MRC-5 cells after transfection with pc-IRAK1 and sh-IRAK1. The effects of miR-206 and IRAK1 on MEK/ERK and JNK pathways were determined by western blot assay. RESULTS: LPS significantly triggered inflammation injury in MRC-5 cells by inhibiting cell viability, suppressing the healing of scratches, inducing cell apoptosis, down-regulating Bcl-2 expression and up-regulating Bax, cleaved-Caspase-3 and cleaved-Caspase-9 expression, and concurrently increasing the concentrations and the protein levels of IL-6 and IL-8. MiR-206 overexpression aggravated LPS-induced inflammation injury in MRC-5 cells. Up-regulation of IRAK1 was observed in miR-206 mimic-transfected cells. Moreover, IRAK1 overexpression promoted LPS-induced inflammation injury in MRC-5 cells. MiR-206 activated MEK/ERK and JNK pathways by regulating IRAK1. CONCLUSIONS: MiR-206 promotes LPS-induced inflammation injury through regulation of IRAK1 in MRC-5 cells.

[Regional Evolution and Control Factors of Karst Groundwater in Liulin Spring Catchment].

The Liulin Spring is one of the ten most famous karst springs in the Shanxi province. The abundant karst groundwater resources support the economic and social development in the Luliang Prefecture. Therefore, the study of evolution and control factors of karst groundwater is of great significance to the sustainable utilization of water resources in the watershed. For revealing the evolution and control factors of karst groundwater in the Liulin Spring area, the main ion components of 29 karst groundwater samples from spring supply area, runoff area, discharge area, and deep buried area were analyzed. The results showed that the temperature and Na+, Ca2+, Mg2+, Cl-, HCO3-, and SO42- concentrations increased continuously along the runoff route, from the recharge area to the runoff area, to the discharge area, and then to the deep burial area. K+, Na+, and Cl- mainly come from salt rock dissolution, and Ca2+, Mg2+, HCO3-, and SO42- mainly come from the dissolution of calcite, dolomite, and gypsum. Because they are controlled by the continuous dissolution of salt rock and gypsum, the concentration of Na+, Cl-, and SO42- in groundwater has increased greatly, with the maximum value being 50 times, 80 times, and 32 times of the minimum value, respectively. Under the influence of dedolomitization, the concentration of Ca2+ and HCO3- in groundwater does not change significantly, the maximum is 2-3 times of the minimum. In the recharge area and runoff area, Na+ and Cl- amounts are lower, and Ca2+ and HCO3- are the main cations and anions in the groundwater. However, in the discharge area and deep buried area, Cl- and Na+ exceed HCO3-, Ca2+, and Mg2+ and become the main anions and cations in the groundwater. The hydrochemical type changes from HCO3-Ca·Mg in the supply area to HCO3·SO4-Ca·Mg in the runoff area, to HCO3·SO4-Ca·Na·Mg in the recharge area, and finally to Cl·HCO3-Na·Ca, Cl·HCO3-Na, and Cl-Na·Ca in the deep burial area.

A Sensitive Luminescent Acetylacetone Probe Based on Zn-MOF with Six-Fold Interpenetration.

A novel metal-organic framework {[Zn(XL)2 ](ClO4 )2 ⋅6 H2 O}n (XL=N,N'-bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxdiimide bi(1,2,4-triazole)) was synthesized and structurally characterized, presenting the first example of six-fold interpenetrating 3 D framework with the topology type of sqc6, which displays high thermostability and solvent stability. Additionally, the luminescence investigations reveal that this MOF can sensitively and selectively detect acetylacetone with a detection limit of 1.72 ppm. More importantly, it is rather rare for an MOF-based luminescence probe to serve as a sensor to effectively detect acetylacetone.

Characterization of Liver Metastasis and Its Effect on Targeted Therapy in EGFR-mutant NSCLC: A Multicenter Study.

BACKGROUND: The risk factors for liver metastasis (LM) in patients with non-small-cell lung cancer (NSCLC) remain unknown. Whether LM predicts for the effect of first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in patients with EGFR-mutant NSCLC needs to be explored. PATIENTS AND METHODS: A total of 598 NSCLC patients from 3 centers underwent EGFR testing, and 293 had EGFR-mutant NSCLC. Of the 598 NSCLC patients, 99 had LM; 56 patients with EGFR-mutant NSCLC received EGFR-TKIs as first-line therapy. RESULTS: EGFR mutation was not associated with LM in NSCLC patients (relative ratio, 1.305, P = .261). In the EGFR-mutant group that received first-line EGFR-TKIs, patients with LM had shorter progression-free survival (PFS; 7.5 vs. 11.8 months; P = .0003) and overall survival (OS; 20.8 vs. 30.6 months; P = .0190) than patients without LM. The significant difference in PFS was observed in both patients with EGFR exon 19 deletion (19del) and Leu858Arg mutation (L858R). However, patients with EGFR 19del and LM showed marginally significantly shorter OS (P = .0531) and patients with EGFR L858R and LM had OS similar to that of patients without LM (P = .1883). Regardless of EGFR status, patients with LM who received first-line chemotherapy had PFS and OS similar to those of patients without LM. Univariate analyses identified only never smoking (hazard ratio, 0.536; P = .012) was significantly associated with better OS for patients with NSCLC and LM. CONCLUSION: EGFR mutation is not an independent risk factor for LM in NSCLC patients. However, the presence of LM is a negative predictive factor for first-line EGFR-TKI therapy for patients with EGFR-mutant NSCLC.

Elemene Increases Autophagic Apoptosis and Drug Sensitivity in Human Cisplatin (DDP)-Resistant Lung Cancer Cell Line SPC-A-1/DDP By Inducing Beclin-1 Expression.

Drug resistance is the major obstacle for the successful therapy of lung adenocarcinoma. It was suggested that ß-elemene, a major isoform of elemene, could reverse the drug resistance in lung cancer cells. However, the underlying mechanisms remains poorly known. Here, we aimed to investigate whether elemene is involved in the cisplatin (DDP)-resistance of lung adenocarcinoma cells and further explore the underlying mechanism. The results showed that human lung adenocarcinoma cell line SPC-A-1 and its DDP-resistant strain SPC-A-1/DDP had a similar sensitivity to elemene treatment. Low dose elemene increased the sensitivity of SPC-A-1/DDP cells to DDP, accompanied by a dramatically decrease in expression of multidrug-resistance proteins and cell proliferation, and an increase in cell autophagy and autophagic apoptosis. We found that the expression of Beclin-1, the key regulator of autophagy, was induced by elemene treatment in a dose-dependent manner. Furthermore, we found that Beclin-1 overexpression had a similar effect with elemene treatment on autophagy and autophagic apoptosis in SPC-A-1/DDP cells. In contrast, Beclin-1 knockdown could significantly rescue elemene-induced autophagic apoptosis and counteract elemene-induced sensitivity in SPC-A-1/DDP cells. Our findings demonstrate that elemene can reverses the drug resistance of SPC-A-1/DDP cells via promotion of Beclin-1-induced autophagy.

MicroRNA-338-3p suppresses cell proliferation and induces apoptosis of non-small-cell lung cancer by targeting sphingosine kinase 2.

BACKGROUND: Lung cancer is the major cause of cancer-related death worldwide, and 80% patients of lung cancer are non-small-cell lung cancer (NSCLC) cases. MicroRNAs are important gene regulators with critical roles in diverse biological processes, including tumorigenesis. Studies indicate that sphingosine kinase 2 (SphK2) promotes tumor progression in NSCLC, but how this occurs is unclear. Thus, we explored the effect of miR-338-3p targeting SphK2 on proliferation and apoptosis of NSCLC cells. METHODS: Expression of miR-338-3p and SphK2 in NSCLC A549 and H1299 cell lines was measured using qRT-PCR and Western blot. CCK-8 and colony formation assays were used to assess the effect of miR-338-3p on NSCLC cell line proliferation. Flow cytometry was used to study the effect of miR-338-3p on NSCLC apoptosis. Luciferase reporter assay and Western blot were used to confirm targeting of SphK2 by miR-338-3p. Finally, in vivo tumorigenesis studies were used to demonstrate subcutaneous tumor growth. RESULTS: miR-338-3p expression in 34 NSCLC clinical samples was downregulated and this was correlated with TNM stage. miR-338-3p significantly suppressed proliferation and induced apoptosis of NSCLC A549 and H1299 cells in vitro. SphK2 was a direct target of miR-338-3p. Overexpression of miR-338-3p significantly inhibited SphK2 expression and reduced luciferase reporter activity containing the SphK2 3'-untranslated region (3'-UTR) through the first binding site. SphK2 lacking 3'-UTR restored the effects of miR-338-3p on cell proliferation inhibition. miR-338-3p significantly inhibited tumorigenicity of NSCLC A549 and H1299 cells in a nude mouse xenograft model. CONCLUSIONS: Collectively, miR-338-3p inhibited cell proliferation and induced apoptosis of NSCLC cells by targeting and down-regulating SphK2, and miR-338-3p could inhibit NSCLC cells A549 and H1299 growth in vivo, suggesting a potential mechanism of NSCLC progression. Therapeutically, miR-338-3p may serve as a potential target in the treatment of human lung cancer.