Protective effects of ginsenoside F2 on isoproterenol-induced myocardial infarction by activating the Nrf2/HO-1 and PI3K/Akt signaling pathways.

BACKGROUND: Ginsenoside F2 (GF2) serves as the principal intestinal metabolite resulting from the oral intake of Panax ginseng and Panax quinquefolius, exhibiting antioxidative, hypolipidemic, antitumor, and anti-inflammatory properties. Nevertheless, its effect on myocardial infarction (MI) is still unknown. PURPOSE: The purpose of this study is to investigate the protective effect and the underlying mechanisms of GF2 against isoproterenol (ISO)-induced MI. METHODS: ISO-induced H9c2 cardiomyocytes and MI rat models were utilized as in vitro and in vivo models to evaluate the impact of anti-MI of GF2. The underlying mechanisms were investigated using a variety of methodologies, including electrocardiography, Western blot analysis, histopathological examination, immunofluorescence, immunohistochemistry, and ELISA techniques. RESULTS: In vivo experiments, our results indicated that GF2 significantly ameliorated ISO-induced electrocardiographic (ECG) abnormalities, myocardial fiber necrosis, rupture, fibrosis of myocardial tissues, and suppressed cardiac enzyme activities. Meanwhile, GF2 notably raised the activity of antioxidant enzymes like CAT, GSH, and SOD. Furthermore, it downregulated Keap1 expression level while upregulating NQO1, Nrf2, and HO-1 expression levels. Additionally, GF2 suppressed the expression of the cleaved caspase-3 and pro-apoptotic protein Bax while promoting the expression of anti-apoptotic proteins Bcl-2, p-PI3K, and p-Akt. TUNEL fluorescence results also demonstrated that GF2 effectively inhibited cardiomyocyte apoptosis. Furthermore, consistent with the results of animal experiments, GF2 considerably attenuated ROS generation, changed apoptosis and mitochondrial function, and reduced oxidative stress in ISO-induced H9c2 cardiomyocytes through activating Nrf2/HO-1 and PI3K/Akt signaling pathways. CONCLUSION: Taken together, GF2 ameliorated MI by preventing cardiocyte apoptosis, oxidative stress, and mitochondrial dysfunction via modulating the Nrf2/HO-1 and PI3K/Akt signaling pathways, showing potential as a treatment strategy for treating MI.

Red-to-blue colorimetric probe based on biomass carbon dots for smartphone-integrated optosensing of Cu(II) and L-cysteine.

We constructed a smartphone-integrated optosensor with inexpensive, reversible, environmental friendly, and rapid adsorption to detect Cu(II) and L-cysteine (L-Cys). The key part of this study was to prepare a red-to-blue colorimetric probe from herbaceous andrographis paniculata using one-pot polymerization at room temperature. When Cu(II) existed, the red fluorescence on the surface of the core-shell probe was quenched, while the blue fluorescence of the core did not respond, because the colorimetric probe interacted with the Cu(II) on the surface of red CDs. After L-Cys added, it interacted with the Cu(II) to strip it from the surface of red CDs, resulting in the recovery of fluorescence response. Under optimal conditions, the detection limits of this method for Cu(II) and L-Cys were 71 nM and 12 nM, respectively. Further, the red-to-blue colorimetric probe was integrated into smartphone with a software application to convert fluorescent color images into specific red (R), green (G), and blue (B) values. The spiked recovery of Cu(II) and L-Cys in lake water was verified the feasibility of the developed optosensors with a recovery of 98.2-101.6 % and 103.3-121.6 %. This method for detecting Cu(II) and L-Cys can not only recognize metal ions from actual samples, but also effectively protect CDs from quenching and restore fluorescence.

Energy-efficient Preparation of Amino and Sulfhydryl Functionalized Biomass Carbon Dots via a Reverse Microemulsion for Specific Recognition of Fe3+ and L-cysteine.

Amino- and sulfhydryl- functionalized biomass carbon dots (BCDs) were prepared by one-pot reverse microemulsion for specific recognition of ferric ions (Fe3+) and L-cysteine (L-Cys). Green grapefruit peel was used as the carbon source while aminosilane and mercaptosilane were used as N- and S-supplier. Following the adsorption of Fe3+ on the surfaces of BCDs-NH2 and BCDs-SH, the fluorescence responses was quenched step by step, while adding L-Cys to the BCDs-NH2/Fe3+ system restored the fluorescence. The BCDs-NH2 and BCDs-SH system exhibited extremely low limits of detection for Fe3+ of 3.2 and 3.0 nM, respectively, within a wide linear ranges of 0.006-200 µM and 0.004-200 µM, respectively. The BCDs-NH2/Fe3+ systems were used as an optosensor for L-Cys in the concentration ranges of 0.08-30 and 30-1000 µM with a detection limit of 65 nM. Developed BCDs-NH2 and BCDs-SH were able to respond to Fe3+ in water samples with satisfactory recoveries of 100.1%-103.1% and 94.6%-108.5%, respectively, and the BCDs-NH2/Fe3+ system was also able to respond to BCDs-NH2/Fe3+ in actual lake water samples with recoveries from 87.3% to 98.8%. Meanwhile, The BCDs-NH2 exhibited good photoluminescence and stability, and the with a fluorescence quantum yield was as high as 25%. This work demonstrates the feasibility of using such materials to remove hazardous ions from water and employing the resulting complexes for optosensing in a sustainable manner.

Comparative transcriptome analysis reveals key genes for polyphyllin difference in five Paris species.

Paris species accumulate a large amount of steroidal saponins, which have numerous pharmacological activities and have become an essential component in many patented drugs. However, only two among all Paris species. Paris are identified as official sources due to high level of bioactive compounds. To clarify the composition of steroidal saponins and the molecular basis behind the differences between species, we investigated transcriptome and metabolic profiles of leaves and rhizomes in Paris polyphylla var. chinensis (PPC), Paris polyphylla var. yunnanensis (PPY), Paris polyphylla var. stenophylla (PPS), Paris fargesii (PF), and Paris mairei (PM). Phytochemical results displayed that the accumulation of steroidal saponins was tissue- and species-specific. PF and PPS contained more steroidal saponins in leaves than rhizomes, while PPY accumulated more steroidal saponins in rhizomes than leaves. PPC and PM contained similar amounts of steroidal saponins in leaves and rhizomes. Transcriptome analysis illustrated that most differentially expressed genes related to the biosynthesis of steroidal saponins were abundantly expressed in rhizomes than leaves. Meanwhile, more biosynthetic genes had significant correlations with steroidal saponins in rhizomes than in leaves. The result of CCA indicated that ACAT, DXS, DWF1, and CYP90 constrained 97.35% of the variance in bioactive compounds in leaves, whereas CYP72, UGT73, ACAT, and GPPS constrained 98.61% of the variance in phytochemicals in rhizomes. This study provided critical information for enhancing the production of steroidal saponins by biotechnological approaches and methodologies.

Carbon Quantum Dots from Pomelo Peel as Fluorescence Probes for "Turn-Off-On" High-Sensitivity Detection of Fe3+ and L-Cysteine.

This study designed a "turn-off-on" fluorescence analysis method based on carbon quantum dots (CQDs) to detect metal ions and amino acids in real sample systems. CQDs were derived from green pomelo peel via a one-step hydrothermal process. The co-doped CQDs with N and S atoms imparted excellent optical properties (quantum yield = 17.31%). The prepared CQDs could be used as fluorescent "turn-off" probes to detect Fe3+ with a limit of detection of 0.086 µM, a linear detection range of 0.1-160 µM, and recovery of 83.47-106.53% in water samples. The quenched CQD fluorescence could be turned on after adding L-cysteine (L-Cys), which allowed detection of L-Cys with a detection limit of 0.34 µM and linear range of 0.4-85 µM. Recovery of L-Cys in amino acid beverage was 87.08-122.74%. Visual paper-based testing strips and cellulose/CQDs composite hydrogels could be also used to detect Fe3+ and L-Cys.

Ameliorative Effects of Malonyl Ginsenoside from Panax ginseng on Glucose-Lipid Metabolism and Insulin Resistance via IRS1/PI3K/Akt and AMPK Signaling Pathways in Type 2 Diabetic Mice.

Our previous study has revealed that malonyl-ginsenosides from Panax ginseng (PG-MGR) play a crucial role in the treatment of T2DM. However, its potential mechanism was still unclear. In this study, we investigated the anti-diabetic mechanisms of action of PG-MGR in high fat diet-fed (HFD) and streptozotocin-induced diabetic mice and determined the main constituents of PG-MGR responsible for its anti-diabetic effects. Our results showed that 16 malonyl ginsenosides were identified in PG-MGR by HPLC-ESI-MS/MS. PG-MGR treatment significantly reduced fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels and improved insulin resistance and glucose tolerance. Simultaneously, PG-MGR treatment improved liver injury by decreasing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) expression. Furthermore, Western blot analysis demonstrated that the protein expression levels of p-PI3K/PI3K, p-AKT/AKT, p-AMPK/AMPK, p-ACC/ACC and GLUT4 in liver and skeletal muscle were significantly up-regulated after PG-MGR treatment, and the protein expression levels of p-IRS-1/IRS-1, Fas and SREBP-1c were significantly reduced. These findings revealed that PG-MGR has the potential to improve glucose and lipid metabolism and insulin resistance by activating the IRS-1/PI3K/AKT and AMPK signal pathways.

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.

Piperlongumine inhibits the growth of non-small cell lung cancer cells via the miR-34b-3p/TGFBR1 pathway.

BACKGROUND: Non-small cell lung cancer is a common type of lung cancer. Piperlongumine (PL), which is extracted from the roots of piperaceae plant, long pepper, and peppercorn, is an alkaloid amide that inhibits tumor growth and metastasis. However, whether it affects lung cancer cells remains unclear. METHODS: We assessed the effects of PL on the proliferation and apoptosis of A549 and H1299 NSCLC cell lines. RESULTS: PL was mildly toxic to normal human bronchial epithelial cells and significantly suppressed growth and facilitated apoptosis of A549 and H1299 cells. It also upregulated microRNA (miR)-34b-3p and downregulated the transforming growth factor beta type I receptor (TGFBR1). The dual-luciferase reporter assay showed that TGFBR1 is a target gene of miR-34b-3p. Silencing of miR-34b-3p or overexpression of TGFBR1 partially attenuated the effects of PL on A549 and H1299 cells. CONCLUSIONS: PL inhibits proliferation and induces apoptosis of A549 and H1299 cells by upregulating miR-34b-3p and modulating TGFBR1 signaling pathway.

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.

Aberrant expression of hsa_circ_0025036 in lung adenocarcinoma and its potential roles in regulating cell proliferation and apoptosis.

As the most common histological subtype of lung cancer, lung adenocarcinoma remains a tremendous risk to public health, which requires ceaseless efforts to elucidate the potential diagnostic and therapeutic strategies. Circular RNAs (circRNAs) have been identified with emerging roles in tumorigenesis and development. Our preliminary work noticed that hsa_circ_0025036 was significantly upregulated in lung adenocarcinoma tissues. However, its specific roles in lung adenocarcinoma remain unclear. The results in this study revealed that hsa_circ_0025036 existed as a circular form and was aberrantly upregulated in lung adenocarcinoma tissues via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Its expression level exhibited a close link with aggressive clinicopathological parameters including cancer differentiation, TNM stage and lymph node metastasis. hsa_circ_0025036 knockdown significantly suppressed cell proliferation and promoted cell apoptosis in A549 and Calu-3 cells. Moreover, hsa_circ_0025036/miR-198/SHMT1&TGF-α axis was identified via bioinformatics analysis and Dual-Luciferase Reporter assays. miR-198 inhibitors reversed the function of hsa_circ_0025036 knockdown. hsa_circ_0025036 knockdown exerted similar effects with miR-198 upregulation on cell proliferation and apoptosis. In conclusion, we demonstrate that hsa_circ_0025036 regulates cell proliferation and apoptosis in lung adenocarcinoma cells probably via hsa_circ_0025036/miR-198/SHMT1&TGF-α axis. hsa_circ_0025036 may serve as a potential prognostic biomarker and a therapeutic target for lung adenocarcinoma.

Membrane permeabilization design of antimicrobial peptides based on chikungunya virus fusion domain scaffold and its antibacterial activity against gram-positive Streptococcus pneumoniae in respiratory infection.

The structural dynamics of membrane permeabilization are investigated systematically and compared between viral fusion peptides (VFPs) and antimicrobial peptides (AMPs). It is revealed that the permeabilization process can be divided into two phases: a fast motion phase in water (first phase) and a slow diffusion phase in lipid (second phase). Difference in peptide permeability to neutrally or weakly charged mammalian membrane and to negatively charged bacterial membrane is primarily determined by the first phase, which is dominated by the direct electrostatic interaction between peptide and the hydrophilic surface of membranes. With the harvested knowledge we attempt to rationally design anti-Gram-positive AMPs based on the VFP scaffold of Chikungunya virus fusion domain, which is an 18-mer polypeptide segment (VT18, 84VYPFMWGGAYCFCDAENT101) located in the structural glycoprotein E1 of viral envelope. Our simulations and previous NMR study suggest that the isolated VT18 peptide can be well structured into a double-stranded ß-sheet conformation in water, but would become intrinsically disordering in lipid. Converting the negatively charged VT18 (charge = -2) to two positively charged peptides VT18-KKLV (VYPFMWGGAYCFCKAKLV-NH2) (charge = +3) and VT18-CAKKLV (VYPFCWGGAYAFCKAKLV-NH2) (charge = +3) by residue substitution and C-terminal amidation can largely promote peptide approaching to bacterial membrane surface, thus rendering the peptide with a substantially increased antibacterial activity against Gram-positive Streptococcus pneumoniae (MIC changes from >200 to 52-105 and 58-90 µg/ml, respectively). A further cyclization of linear peptide VT18-CAKKLV by adding a disulfide bond across its two strand arms, which results in a cyclic peptide cVT18-CAKKLV () (charge = +3), can effectively stabilize the peptide ß-sheet conformation in lipid, thus improving its membrane compatibility in second phase and enhancing its antibacterial potency (MIC = 35-67 µg/ml). We also demonstrated that the designed AMPs have no or only a moderate cytotoxic effect and hemolytic activity on human normal cells.

Long Noncoding RNA RGMB-AS1 Indicates a Poor Prognosis and Modulates Cell Proliferation, Migration and Invasion in Lung Adenocarcinoma.

Lung cancer is the most common cause of cancer-related mortality worldwide. It is a complex disease involving multiple genetic and epigenetic alterations. The development of transcriptomics revealed the important role of long non-coding RNAs (lncRNAs) in lung cancer occurrence and development. Here, microarray analysis of lung adenocarcinoma tissues showed the abnormal expression of lncRNA RGMB-AS1. However, the role of lncRNA RGMB-AS1 in lung adenocarcinoma remains largely unknown. We showed that upregulation of lncRNA RGMB-AS1 was significantly correlated with differentiation, TNM stage, and lymph node metastasis. In lung adenocarcinoma cells, downregulation of lncRNA RGMB-AS1 inhibited cell proliferation, migration, invasion, and caused cell cycle arrest at the G1/G0 phase. In vivo experiments showed that lncRNA RGMB-AS1 downregulation significantly suppressed the growth of lung adenocarcinoma. The expression of lncRNA RGMB-AS1 was inversely correlated with that of repulsive guidance molecule b (RGMB) in lung adenocarcinoma tissues, and UCSC analysis and fluorescence detection assay indicated that lncRNA RGMB-AS1 may be involved in the development of human lung adenocarcinoma by regulating RGMB expression though exon2 of RGMB. In summary, our findings indicate that lncRNA RGMB-AS1 may play an important role in lung adenocarcinoma and may serve as a potential therapeutic target.

miR-198 targets SHMT1 to inhibit cell proliferation and enhance cell apoptosis in lung adenocarcinoma.

MiR-198 is involved in tumorigenesis, migration, invasion, and metastasis of various malignant cancers. However, the exact expression levels of miR-198 and the molecular mechanism underlying its role in lung adenocarcinoma require further exploration. In this study, quantitative real-time PCR was applied to study miR-198 and serine hydroxymethyltransferase 1 (SHMT1) expression in 47 paired lung adenocarcinoma tissues and adjacent nontumor lung tissues. Clinicopathological characters were analyzed. Pearson's correlation analysis was used to detect the relationship between miR-198 and SHMT1 expression. The function of miR-198 was explored by measuring cell proliferation, cell apoptosis, and the cell-cycle in vitro and in vivo. The target gene of miR-198 was certified using dual luciferase report assay. We found that in lung adenocarcinoma, miR-198 was significantly downregulated and SHMT1 was inversely upregulated. A strong negative correlation was noticed between miR-198 and SHMT1 expression. Further analysis revealed that miR-198 expression was associated with TNM stage and lymph node metastasis. Upregulated miR-198 could inhibit cell proliferation, enhance cell apoptosis, and lead to cell-cycle arrest in lung adenocarcinoma, which showed a more effective alteration than SHMT1 siRNA. Moreover, we identified SHMT1 as a target gene of miR-198. In conclusion, miR-198 suppressed proliferation of lung adenocarcinoma cells both in vitro and in vivo by directly targeting SHMT1. miR-198 may be a potential therapeutic target for lung adenocarcinoma in the near future.

Anticancer function of α-solanine in lung adenocarcinoma cells by inducing microRNA-138 expression.

Currently, lung cancer is still a main cause of malignancy-associated death worldwide. Even though various methods for prevention and treatment of lung cancer have been improved in recent decades, the 5-year survival rate has remained very low. Insights into the anticancer function of small-molecule anticancer compounds have opened our visual field about cancer therapy. α-Solanine has been well studied for its antitumor properties, but its effect in lung cancer and associated molecular mechanisms have not yet been evaluated. To explore the anticancer function of α-solanine, we performed an MTT assay, Transwell arrays, colony-forming survival assay, quantitative reverse transcription PCR (qRT-PCR), Western blotting, and dual luciferase reporter assays in A549 and H1299 cells. We found that α-solanine not only inhibited cell migration and invasion ability but also enhanced the chemosensitivity and radiosensitivity of A549 and H1299 cells. Moreover, we discovered that α-solanine could affect the expression of miR-138 and focal adhesion kinase (FAK), both of which were also found to affect the chemosensitivity and radiosensitivity of A549 and H1299 cells. In conclusion, α-solanine could affect miR-138 and FAK expression to restrict cell migration and invasion and enhance the chemosensitivity and radiosensitivity of A549 and H1299 cells. The α-solanine/miR-138/FAK cascade can probably be a potential therapy target against lung adenocarcinoma.

A Stretchable Electronic Fabric Artificial Skin with Pressure-, Lateral Strain-, and Flexion-Sensitive Properties.

A stretchable and multiple-force-sensitive electronic fabric based on stretchable coaxial sensor electrodes is fabricated for artificial-skin application. This electronic fabric, with only one kind of sensor unit, can simultaneously map and quantify the mechanical stresses induced by normal pressure, lateral strain, and flexion.

microRNA-30b inhibits cell invasion and migration through targeting collagen triple helix repeat containing 1 in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the largest histological subgroup of lung cancer and has increased in prevalence in China over the past 5 years. The 5-year survival rate has remained at 15-20 %, with a median survival of 8-12 months. The tumorigenesis and progression of NSCLC is orchestrated by numerous oncogene and anti-oncogene mutations and insights into microRNA function have increased our understanding of the process. Here, we investigated the effects of miR-30b on NSCLC cell invasion and migration and explored the underlying molecular mechanisms involved. METHODS: Quantitative reverse transcription PCR, wound healing assay, trans-well assays, western blotting and dual luciferase assays were performed to investigate the molecular mechanisms of miR-30b in NSCLC cells. RESULTS: MiR-30b was down-regulated and Cthrc1 up-regulated in NSCLC tissues. Both were associated with tumor differentiation, TNM stage and lymph node metastases. Up-regulation of miR-30b restricted A549 and Calu-3 cell invasion and migration. Additionally, the expression of Cthrc1, matrix metalloproteinase-9 and matrix metalloproteinase-2 was reduced, while metallopeptidase inhibitor-1 expression increased. Bioinformatics analysis identified Cthrc1 as a target of miR-30b and western blotting and luciferase reporter assays confirmed that miR-30b regulates Cthrc1 by directly binding to its 3'UTR. Transfection of Cthrc1 without the 3'UTR restored the miR-30b inhibiting cell invasion. Up-regulation of miR-30b or down-regulation of Cthrc1 had potential significance in the invasion and metastasis of NSCLC. CONCLUSIONS: MiR-30b was down-regulated and Cthrc1 up-regulated in NSCLC tissues. Both of them were related to tumor differentiation, TNM stage and lymph node metastases. MiR-30b affected NSCLC cells invasion and migration by regulating Cthrc1.

Study on expression of lncRNA RGMB-AS1 and repulsive guidance molecule b in non-small cell lung cancer.

BACKGROUND: The relationships between lncRNAs and tumors have currently become one of the focuses on cancer studies. However, there are a few studies about lncRNAs in non-small cell lung cancer (NSCLC) at present. METHODS: Microarray analysis was designed to study the expression patterns of lncRNAs in three pairs of NSCLC tissues. The expression of lncRNA RGMB-AS1 and repulsive guidance molecule b (RGMB) were detected in 72 paired NSCLC tissues and adjacent normal tissues by qRT-PCR assay. The relations of lncRNA RGMB-AS1 and RGMB expression with clinicopathological factors of NSCLC patients were explored. A549 and SPC-A-1 cells were transfected with siRNA of lncRNA RGMB-AS1 and negative control. RGMB expression level was detected by qRT-PCR assay and western blot analysis. RESULTS: The results of microarray found that 571 lncRNAs were differentially expressed in NSCLC tissues (Fold change cut-off: 5.0, P < 0.05), including 304 upregulated and 267 downregulated lncRNAs. The results of qRT-PCR showed that lncRNA RGMB-AS1 expression was significantly higher in NSCLC tissues than in adjacent normal tissues (P < 0.05), while RGMB mRNA showed an opposite trend (P < 0.05). Correlation analysis indicated that the expression of lncRNA RGMB-AS1and RGMB mRNA were inversely correlated (R(2) = 0.590, P < 0.05). While lncRNA RGMB-AS1 and RGMB expression levels in NSCLC tissues were associated with the occurrence of differentiation status, lymph node metastases and TNM stage (P < 0.05). Transfection with siRNA of lncRNA RGMB-AS1, subsequent results showed that RGMB mRNA and protein expression were upregulated (P < 0.05) in A549 and SPC-A-1 cells compared to the control groups. CONCLUSION: We identified lncRNA RGMB-AS1 was upregulated and RGMB was downregulated in NSCLC patients. Both were related to differentiation status, lymph node metastases and TNM stage. Studies also indicated that lncRNA RGMB-AS1and RGMB were inversely correlated. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7911587521528276.

Ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to γ-radiation by targeting the nuclear factor-κB pathway.

At present, it is elusive how non-small cell lung cancer (NSCLC) develops resistance to γ-radiation; however, the transcription factor nuclear factor-κB (NF-κB) and NF-κB-regulated gene products have been proposed as mediators. Ginsenoside Rg3 is a steroidal saponin, which was isolated from Panax ginseng. Ginsenoside Rg3 possesses high pharmacological activity and has previously been shown to suppress NF-κB activation in various types of tumor cell. Therefore, the present study aimed to determine whether Rg3 could suppress NF-κB activation in NSCLC cells and sensitize NSCLC to γ-radiation, using an NSCLC cell line and NSCLC xenograft. A clone formation assay and lung tumor xenograft experiment were used to assess the radiosensitizing effects of ginsenoside Rg3. NF-κB/inhibitor of NF-κB (IκB) modulation was ascertained using an electrophoretic mobility shift assay and western blot analysis. NF-κB-regulated gene products were monitored by western blot analysis. The present study demonstrated that ginsenoside Rg3 was able to sensitize A549 and H1299 lung carcinoma cells to γ-radiation and significantly enhance the efficacy of radiation therapy in C57BL/6 mice bearing a Lewis lung carcinoma cell xenograft tumor. Furthermore, ginsenoside Rg3 suppressed NF-κB activation, phosphorylation of IκB protein and expression of NF-κB-regulated gene products (cyclin D1, c-myc, B-cell lymphoma 2, cyclooxygenase-2, matrix metalloproteinase-9 and vascular endothelial growth factor), a number of which were induced by radiation therapy and mediate radioresistance. In conclusion, the results of the present study suggested that ginsenoside Rg3 may potentiate the antitumor effects of radiation therapy in NSCLC by suppressing NF-κB activity and NF-κB-regulated gene products, leading to the inhibition of tumor progression.