Effect of water-soluble polymers on the transport of functional group-modified polystyrene nanoplastics in goethite-coated saturated porous media.

The research on the impact of water-soluble polymers (WSPs) on the migration and fate of plastic particles is extremely limited. This article explored the effects of polyacrylic acid (PAA, a common WSP) and physicochemical factors on the transport of polystyrene nanoparticles (PSNPs-NH2/COOH) with different functional groups in QS (quartz sand) and FOS (goethite-modified quartz sand, simulates mineral colloids). Research has shown that PAA can selectively adsorb onto the surface of PSNPs-NH2, forming ecological corona heterogeneous aggregates. This process increased the spatial hindrance and elastic repulsion, resulting in the recovery of PSNPs-NH2 always exceeding that of PSNPs-COOH. Overall, PAA can hinder the migration of PSNPs in QS but can promote their migration in FOS. When multivalent cations coexist with PAA, the transport of PSNPs in the media is primarily affected by cation bridging and CH-cation-π interaction. The presence of oxyanions and PAA prevents PSNPs from following the Hofmeister rule and promotes their migration (PO43-: 82.34 ± 0.16% to 94.63 ± 2.82%>SO42-: 81.38 ± 2.73% to 91.15 ± 0.93%>NO3-: 55.85 ± 0.70%-87.16 ± 3.80%). The findings of this study contribute significantly to a better understanding of the migration of WSPs and group-modified NPs in complex saturated porous media.

Modeling the feasibility of Se-rich corn cultivation in Se-deficient agricultural fields using random forest algorithm.

Selenium constitutes an essential trace element for the human body. Moderate Se intake plays a pivotal role in preserving overall health. The absorption of Se by plants is primarily influenced by the available Se levels in soils, rather than by the soil total Se content, offering potential for exploring Se-rich crops in Se-deficient regions. In this study, we explore the factors influencing the Se bioaccumulation coefficient in corn based on a land quality geochemical survey at a 1:50,000 scale and establish predictive models for corn seed Se content using random forest and multiple linear regression approaches. The results indicate that the surface soil in the study area is deficient in Se (0.18-1.21 mg/kg), but 54% of the corn grain samples met the standards for Se-rich products (0.02-0.30 mg/kg). The factors influencing the Se biological enrichment coefficient in corn seeds are soil pH and CaO and MgO content, with impact levels of 0.54, 0.42, and 0.35, respectively. Compared to multiple linear regression models, the RF model provides more accurate and reliable predictions of corn Se content. The random forest model indicates that approximately 41% of the farmland within the study area is conducive to the cultivation of naturally Se-rich corn, which is a 26% increase in the planting area compared to recommendations based solely on soil Se content. In this research, we introduce an innovative methodological framework for organically cultivating naturally Se-rich corn within regions affected by Se deficiency.

Colchicine protects against the development of experimental abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is characterized by at least 1.5-fold enlargement of the infrarenal aorta, a ruptured AAA is life-threatening. Colchicine is a medicine used to treat gout and familial Mediterranean fever, and recently, it was approved to reduce the risk of cardiovascular events in adult patients with established atherosclerotic disease. With an AAA mice model created by treatment with porcine pancreatic elastase (PPE) and ß-aminopropionitrile (BAPN), this work was designed to explore whether colchicine could protect against the development of AAA. Here, we showed that colchicine could limit AAA formation, as evidenced by the decreased total aortic weight per body weight, AAA incidence, maximal abdominal aortic diameter and collagen deposition. We also found that colchicine could prevent the phenotypic switching of vascular smooth muscle cells from a contractile to synthetic state during AAA. In addition, it was demonstrated that colchicine was able to reduce vascular inflammation, oxidative stress, cell pyroptosis and immune cells infiltration to the aortic wall in the AAA mice model. Finally, it was proved that the protective action of colchicine against AAA formation was mainly mediated by preventing immune cells infiltration to the aortic wall. In summary, our findings demonstrated that colchicine could protect against the development of experimental AAA, providing a potential therapeutic strategy for AAA intervention in the clinic.

FAM72 family proteins as poor prognostic markers in clear cell renal carcinoma.

Purpose: This study aimed to investigate the prognostic significance of the Family with Sequence Similarity 72 member (FAM72) gene family in clear cell renal carcinoma (ccRCC) using a bioinformatic approach. Patients and methods: To investigate the association between FAM72 and ccRCC, we utilized various databases and analysis tools, including TCGA, GEPIA, Metscape, cBioPortal, and MethSurv. We conducted an analysis of FAM72 expression levels in ccRCC tissues compared to normal kidney tissues and performed univariate and multivariate Cox analysis to determine the relationship between FAM72 expression and patient prognosis. Furthermore, we carried out Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) to identify enriched biological processes associated with FAM72 expression. Additionally, we analyzed immune cell infiltration and the level of methylation in ccRCC patients. Our bioinformatic analysis revealed that FAM72 expression levels were significantly higher in ccRCC tissues than in normal kidney tissues. High expression of FAM72 was associated with poor prognosis in ccRCC patients and was found to be an independent prognostic factor for ccRCC. GO and GSEA analyses indicated that FAM72 was enriched in biological processes related to mitosis, cell cycle, and DNA metabolism. Moreover, we found a significant correlation between FAM72 and immune cell infiltration and the level of methylation in ccRCC patients. Conclusion: Our findings suggest that FAM72 could serve as an unfavorable prognostic molecular marker for ccRCC. A comprehensive understanding of FAM72 could provide crucial insights into tumor progression and prognosis.

Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition.

Cuproplasia, or copper-dependent cell proliferation, has been observed in varieties of solid tumors along with aberrant copper homeostasis. Several studies reported good response of patients to copper chelator assisted neoadjuvant chemotherapy, however, the internal target molecules are still undetermined. Unravel copper-associated tumor signaling would be valuable to forge new links to translate biology of copper into clinical cancer therapies. We evaluated the significance of high-affinity copper transporter-1 (CTR1) by bioinformatic analysis, and in 19 pairs of clinical specimens. Then, with the help of gene interference and chelating agent, enriched signaling pathways were identified by KEGG analysis and immunoblotting. Accompanying biological capability of pancreatic carcinoma-associated proliferation, cell cycle, apoptosis, and angiogenesis were investigated. Furthermore, a combination of mTOR inhibitor and CTR1 suppressor has been assessed in xenografted tumor mouse models. Hyperactive CTR1 was investigated in pancreatic cancer tissues and proven to as the key point of cancer copper homeostasis. Intracellular copper deprivation induced by CTR1 gene knock-down or systematic copper chelation by tetrathiomolybdate suppressed proliferation and angiogenesis of pancreatic cancer cell. PI3K/AKT/mTOR signaling pathway was suppressed by inhibiting the activation of p70(S6)K and p-AKT, and finally inhibited mTORC1 and mTORC2 after copper deprivation. Additionally, CTR1 gene silencing successfully improved the anti-cancer effect of mTOR inhibitor rapamycin. Our study reveals that CTR1 contributes to pancreatic tumorigenesis and progression, by up-regulating the phosphorylation of AKT/mTOR signaling molecules. Recovering copper balance by copper deprivation addresses as promising strategy for improved cancer chemotherapy.

Circ_0005276 Promotes Prostate Cancer Progression Through the Crosstalk of miR-128-3p/DEPDC1B Axis.

This study aimed to investigate more detailed functions of circ_0005276 in prostate cancer (PCa) and provide a novel mechanism for circ_0005276 action. The expression of circ_0005276, microRNA-128-3p (miR-128-3p) and DEP domain containing 1B (DEPDC1B) was detected by quantitative real-time PCR. In functional assays, cell proliferation was determined by CCK-8 assay and EdU assay. Cell migration and invasion were determined by transwell assay. The ability of angiogenesis was determined by tube formation assay. Cell apoptosis was determined by flow cytometry assay. The potential binding relationship between miR-128-3p and circ_0005276 or DEPDC1B was ascertained by dual-luciferase reporter assay and RIP assay. Mouse models were used to verify the role of circ_0005276 in vivo. The upregulation of circ_0005276 was determined in PCa tissues and cells. Circ_0005276 knockdown inhibited proliferation, migration, invasion and angiogenesis in PCa cells, and circ_0005276 knockdown also blocks tumor growth in vivo. Mechanism analysis discovered that miR-128-3p was a target of circ_0005276, and miR-128-3p inhibition recovered circ_0005276 knockdown-inhibited proliferation, migration, invasion and angiogenesis. In addition, DEPDC1B was a target of miR-128-3p, and miR-128-3p restoration-inhibited proliferation, migration, invasion and angiogenesis were rescued by DEPDC1B overexpression. Circ_0005276 might promote the development of PCa by activating the expression of DEPDC1B via targeting miR-128-3p.

The SARS-CoV-2 nucleocapsid protein: its role in the viral life cycle, structure and functions, and use as a potential target in the development of vaccines and diagnostics.

Coronavirus disease 2019 (COVID-19) continues to take a heavy toll on personal health, healthcare systems, and economies around the globe. Scientists are expending tremendous effort to develop diagnostic technologies for detecting positive infections within the shortest possible time, and vaccines and drugs specifically for the prevention and treatment of COVID-19 disease. At the same time, emerging novel variants have raised serious concerns about vaccine efficacy. The SARS-CoV-2 nucleocapsid (N) protein plays an important role in the coronavirus life cycle, and participates in various vital activities after virus invasion. It has attracted a large amount of attention for vaccine and drug development. Here, we summarize the latest research of the N protein, including its role in the SARS-CoV-2 life cycle, structure and function, and post-translational modifications in addition to its involvement in liquid-liquid phase separation (LLPS) and use as a basis for the development of vaccines and diagnostic techniques.

Exploring the differential effects of career and psychosocial mentoring on newcomer socialization.

Drawing on the social cognitive career theory, this study proposed an integrative framework to uncover how and when different types of mentoring accelerate newcomer's socialization in corresponding domains. We tested this relational model with time-lagged, multisource survey data collected from 157 newcomers and 88 supervisors. The results indicated that career mentoring facilitated newcomer task mastery, task performance, and job satisfaction by improving newcomer occupational self-efficacy, whereas psychosocial mentoring promoted newcomer job satisfaction and social integration via inspiring newcomer social self-efficacy. Furthermore, newcomer learning adaptability amplified the influence of career mentoring on newcomer occupational self-efficacy, as well as the impact of psychosocial mentoring on newcomer social self-efficacy. Our study extended the mentoring and socialization literature and provided significant practical implications for managers on how to arrange tailored mentoring to facilitate newcomer socialization.

High expression of DARS2 indicates poor prognosis in lung adenocarcinoma.

BACKGROUND: DARS2 was overexpressed in multiple tumor types, but the biological role of DARS2 in lung adenocarcinoma (LUAD) have not been elucidated. METHODS: Firstly, the DARS2 expression in LUAD was explored using The Cancer Genome Atlas (TCGA). Then, qRT-PCR and Western blot were performed to confirm DARS2 expression in LUAD. Next, Cox regression and Kaplan-Meier methods were utilized to evaluate whether DARS2 expression can affect the overall survival. The relationships between DARS2 expression and clinicopathological characteristics were investigated by TCGA database. Moreover, we utilized Gene Set Enrichment Analysis (GSEA) to detect DARS2-related signaling pathways in LUAD. Finally, the special function of DARS2 in cell proliferation, invasion and apoptosis was assessed in vitro. RESULTS: The higher expression of DARS2 was found in LUAD compared to para-carcinoma tissues and significantly related to tumor stage, T stage, and M stage. The survival analysis indicated that DARS2 overexpression was related to poor prognosis in LUAD. Multivariate analysis suggested that DARS2 expression was a prognostic indicator. GSEA revealed that DARS2 was primarily involved in cell cycle-related pathways. In addition, upregulation of DARS2 facilitated LUAD cell proliferation, migration, invasion and inhabited apoptosis, DARS2 knockdown showed an opposite result. CONCLUSION: DARS2 modulates the proliferation, invasion and apoptosis of LUAD cells, and sever as a promising therapeutic target for LUAD.

EGCG Enhances the Chemosensitivity of Colorectal Cancer to Irinotecan through GRP78-MediatedEndoplasmic Reticulum Stress.

This study aimed to explore the role of GRP78-mediated endoplasmic reticulum stress (ERS) in the synergistic inhibition of colorectal cancer by epigallocatechin-3-gallate (EGCG) and irinotecan (IRI). Findings showed that EGCG alone or in combination with irinotecan can significantly promote intracellular GRP78 protein expression, reduce mitochondrial membrane potential and intracellular ROS in RKO and HCT 116 cells, and induce cell apoptosis. In addition, glucose regulatory protein 78 kDa (GRP78) is significantly over-expressed in both colorectal cancer (CRC) tumor specimens and mouse xenografts. The inhibition of GRP78 by small interfering RNA led to the decrease of the sensitivity of CRC cells to the drug combination, while the overexpression of it by plasmid significantly increased the apoptosis of cells after the drug combination. The experimental results in the mouse xenografts model showed that the combination of EGCG and irinotecan could inhibit the growth of subcutaneous tumors of HCT116 cells better than the two drugs alone. EGCG can induce GRP78-mediated endoplasmic reticulum stress and enhance the chemo-sensitivity of colorectal cancer cells when coadministered with irinotecan.

The Paradoxical Effects of COVID-19 Event Strength on Employee Turnover Intention.

As a global pandemic, the novel coronavirus (COVID-19) has brought enormous challenges to employees and organizations. Although numerous existing studies have highlighted that the COVID-19 pandemic is a stressful event and empirically proved its detrimental effect on employee turnover intention, few scholars have noted that this pandemic can deteriorate the external economic and employment environment simultaneously, which may further complicate employees' intentions to leave or stay in the current organization. Drawing on event system theory and social cognitive theory, this study aims to uncover two potential cognitive mechanisms of the complex impact of COVID-19 event strength on employee turnover intention. To examine the proposed model, this study employed a three-wave and time-lagged research design and collected data from a sample of 432 employees of four Chinese companies from different industries. The findings indicated that COVID-19 event strength was negatively related to perceived external employability, and ultimately curbed employee turnover intention. Yet, COVID-19 event strength also negatively predicted perceived organizational growth, thus influencing employees to exhibit intentions to quit. Moreover, organizational identification not only attenuated the positive effect of perceived external employability on turnover intention but also amplified the negative impact of perceived organizational growth on turnover intention. Further, organizational identification moderated the indirect effects of COVID-19 event strength on turnover intention through perceived external employability and perceived organizational growth. This study provided a comprehensive insight into scholars' understanding of the COVID-19 downstream outcomes.

Torsional Low-Strain Test for Nondestructive Integrity Examination of Existing High-Pile Foundation.

Low-strain tests are widely utilized as a nondestructive approach to assess the integrity of newly piled foundations. So far, the examination of existing pile foundations is becoming an indispensable protocol for pile recycling or post-disaster safety assessment. However, the present low-strain test is not capable of testing existing pile foundations. In this paper, the torsional low-strain test (TLST) is proposed to overcome this drawback. Both the upward and downward waves are considered in the TLST wave propagation model established in this paper so that a firm theoretical basis is grounded for the test signal interpretations. A concise semi-analytical solution is derived and its rationality is verified by comparisons with the existing solutions for newly piled foundations and the finite element results. The main conclusions of this study can be drawn as follows: (1). by placing the sensors where the incident wave is applied, the number of reflected signals can be minimized; (2). the defects can be more evidently identified if the incident wave/sensors are input/installed close to the superstructure/pile head.

Structure-Dependent Chiroptical Properties of Twisted Multilayered Silver Nanowire Assemblies.

The optical properties of chiral plasmonic metasurfaces depend strongly on their architecture, in particular the orientation and spacing between the individual building blocks assembled into large arrays. However, methods to obtain chiral metamaterials with fully tunable chiroptical properties in the UV, visible, and near-infrared range are scarce. Here, we show that the chiroptical properties of silver nanowires assembled in helical nanostructures by grazing incidence spraying and Layer-by-Layer assembly can be finely tuned over a broad wavelength range using simple design principles. The angle between the oriented nanowire layers controls the intensity of the circular dichroism, reaching ellipticity values higher than 13° and g-factor values up to 1.6, while the shape of the circular dichroism spectra depends strongly on the spacing between the layers which can be tuned at the nanometer scale. The structure-dependent optical properties of the assembly are successfully modeled using a transfer matrix approach.

Nanoscale Bouligand Multilayers: Giant Circular Dichroism of Helical Assemblies of Plasmonic 1D Nano-Objects.

Chirality is found at all length scales in nature, and chiral metasurfaces have recently attracted attention due to their exceptional optical properties and their potential applications. Most of these metasurfaces are fabricated by top-down methods or bottom-up approaches that cannot be tuned in terms of structure and composition. By combining grazing incidence spraying of plasmonic nanowires and nanorods and Layer-by-Layer assembly, we show that nonchiral 1D nano-objects can be assembled into scalable chiral Bouligand nanostructures whose mesoscale anisotropy is controlled with simple macroscopic tools. Such multilayer helical assemblies of linearly oriented nanowires and nanorods display very high circular dichroism up to 13 000 mdeg and giant dissymmetry factors up to g ≈ 0.30 over the entire visible and near-infrared range. The chiroptical properties of the chiral multilayer stack are successfully modeled using a transfer matrix formalism based on the experimentally determined properties of each individual layer. The proposed approach can be extended to much more elaborate architectures and gives access to template-free and enantiomerically pure nanocomposites whose structure can be finely tuned through simple design principles.

EGCG synergizes the therapeutic effect of irinotecan through enhanced DNA damage in human colorectal cancer cells.

Irinotecan is a kind of alkaloid with antitumour activity, but its low solubility and high toxicity limit its application. Epigallocatechin-3-gallate (EGCG) is one of the main bioactive components in tea. The epidemiological investigation and animal and cell experiments show that EGCG has a preventive and therapeutic effect on many kinds of tumours. Here, colorectal cancer cells RKO and HCT116 were employed, and the CCK8 proliferation test was used to screen the appropriate concentration of EGCG and irinotecan, and the effects of single and/or combined drugs on migration, invasion, DNA damage, cell cycle and autophagy of tumour cells were investigated. The results showed that EGCG combined with irinotecan (0.5 µmol L- ) not only had a stronger inhibitory effect on tumour cells than EGCG or irinotecan alone but also prevented tumour cell migration and invasion. EGCG alone did not cause DNA damage in colorectal cancer cells, but its combination with irinotecan could induce S or G2 phase arrest by inhibiting topoisomerase I to cause more extensive DNA damage. EGCG also induced apoptosis by promoting autophagy with irinotecan synergistically. These results indicated that EGCG in combination with irinotecan could be a promising strategy for colorectal cancer.

Linkage Analysis between Finance and Environmental Protection Sectors in China: An Approach to Evaluating Green Finance.

Given the growing awareness of sustainable development, the environmental protection industry has attracted much attention. Green finance has developed rapidly in policymaking and practices. This study provides a framework for evaluating green finance via linkage analysis based on input-output theory. Measurements on industrial linkages are calculated in China in two provinces from 2002 to 2018, which study the relationship between finance and environmental protection sectors. The results show that the environmental protection sector (EPS) in China has gradually developed from a sector with weak backward and strong forward linkages to a sector with strong backward and weak forward linkages from 2002 to 2015; however, in 2017 and 2018, the EPS returned to a sector with weak backward and strong forward linkages. At the provincial level, the EPS used to be a key sector with strong backward and forward linkages. The connection between the finance sector and the EPS rose first, then declined in the country and the Zhejiang province; Guangdong had a similar evolution in the former period, but it had a rising trend in the latest year. The findings provide insights for further promoting the support from the finance sector to the environmental protection activities.

Usnic Acid Inhibits Proliferation and Migration through ATM Mediated DNA Damage Response in RKO Colorectal Cancer Cell.

BACKGROUND: Usnic Acid (UA), also known as lichenol, has been reported to have inhibitory effects on a variety of cancer cells, but its specific mechanism remained to be elucidated. Tumor chemotherapy drugs, especially DNA damage chemotherapeutic drugs, target Chromosomal DNA, but their spontaneous and acquired drug resistance are also an urgent problem to be solved. Therefore, drug combination research has become the focus of researchers. METHODS: Here, we evaluated the tumor-suppressing molecular mechanism of UA in colorectal cancer cells RKO from the perspective of the ATM-mediated DNA damage signaling pathway through H2O2 simulating DNA damage chemotherapeutic drugs. CCK8 cell proliferation assay was used to determine the inhibition of RKO cells by hydrogen peroxide and UA alone or in combination, and wound healing assay was applied to determine the effect of the drug on cell migration. RESULTS: Transfected cells with miRNA18a-5p mimics and inhibitors, MDC and DCFH-DA staining for the measurement of autophagy and ROS, cell cycle and apoptosis were detected by flow cytometry, expressions of microRNA and mRNA were determined by fluorescence quantitative PCR, and protein by Western blot. DISCUSSION: We found that UA can upregulate ATM via miR-18a to activate the DNA damage signaling pathway and inhibit the proliferation and migration of RKO cells in a concentration-dependent manner. CONCLUSION: At the same time, DNA damage responses, including cell cycle, autophagy, apoptosis and ROS levels, are also regulated by UA. Therefore, UA combined with DNA damage chemotherapeutic drugs may be an effective treatment for cancer.

[Inhibition of Copper Transporter-1 by Ammonium Tetrathiocarbolybdate in the Treatment of Pancreatic Cancer].

OBJECTIVE: To examine copper transporter 1 (CTR1) expression in pancreatic carcinoma cells, orthotopic xenograft pancreatic tumor model and clinical samples, and verify the effect of copper chelating agent ammonium tetrathiomolybdate (TM) regulate the expression of CTR1 in pancreatic carcinoma cells and the inhibition of pancreatic carcinoma. METHODS: The expressions of copper transporter CTR1 and antioxidant protein 1 (ATOX1) in 22 clinical pancreatic ductal carcinoma and paracancer tissues 0.5-1 cm away from the tumor were measured by immunohistochemistry (IHC). PANC-1 cells were used to construct 5 orthotopic xenograft pancreatic tumor of nude mice models. Pancreatic cancer tissues and corresponding normal pancreatic tissues were collected, and the expressions of CTR1 and ATOX1 were detected by IHC and compared with clinical tissues. The proliferation of pancreatic carcinoma cells PANC-1 treated with 10, 30, 50, 100 µmol/L TM for 24 h, 48 h, 72 h was measured by CCK8 assay. The migration abilities of PANC-1 cells treated with 50 µmol/L TM for 24 h, 48 h were detected by scratch test. The expressions of CTR1, vascular endothelial growth factor (VEGF) and CyclinD1 proteins in PANC-1 cells treated with 10, 30, 50, 100 µmol/L TM for 48 h were measured by Western blot. Then the subcutaneous tumor-bearing model of nude mice were established with PANC-1 cells, and the growth of tumor was observed after oral administration of 0.3 mg/d and 1.0 mg/d of TM, respectively. RESULTS: The immunohistochemical results indicated that 19 of the 22 clinical pancreatic ductal cancer tissues of carcinoma patients had high expression of CTR1, and the same high expression of CTR1 was found in the orthotopic transplanted tumor tissues of PANC-1 nude mice. The proliferation inhibition of PANC-1 cells increased with the concentration of TM increased and the treatment time prolonged. The expressions of intracellular CTR1, VEGF and CyclinD1 all decreased with the concentration of TM increased. The cell migration ability decreased after the PANC-1 cells treated with TM. The tumor growth of PANC-1 tumor-bearing nude mice was inhibited after different doses of TM were delivered. The reduction in tumor volume and weight was more pronounced in the high-dose TM group (P<0.05). CONCLUSION: The expression of CTR1 is abnormally elevated in pancreatic carcinoma, and treatment with copper chelating agent for this target may help to inhibit pancreatic carcinoma.

Tuning the Chiroptical Properties of Elongated Nano-objects via Hierarchical Organization.

Chiral materials appear as excellent candidates to control and manipulate the polarization of light in optical devices. In nanophotonics, the self-assembly of colloidal plasmonic nanoparticles gives rise to strong resonances in the visible range, and when such organizations are chiral, a strong chiroplasmonic effect can be observed. In the present work, we describe the optical properties of chiral artificial nanophotonic materials, Goldhelices, which are hierarchically organized by grazing incidence spraying. These Goldhelices are made by plasmonic nanoparticles (gold) grafted onto helical templates made from silica nanohelices. A comparison of oriented versus non-oriented surfaces has been performed by Mueller matrix polarimetry, showing the importance of the organization of the Goldhelices regarding their interaction with light. Moreover, mono- versus multilayer photonic films are created, and the measured optical properties are discussed and compared to simulations.

Metformin mediated microRNA-7 upregulation inhibits growth, migration, and invasion of non-small cell lung cancer A549 cells.

Metformin, a medication widely used in the treatment of type 2 diabetes mellitus, has a possible antitumor effect in type 2 diabetes mellitus patients. MicroRNA-7 is a significant microRNA in non-small cell lung cancer. Metformin has an inhibitory effect on lung cancer and regulates the expression of certain microRNAs, but there is no report connecting metformin with microRNA-7 in lung cancer. Thus, we used qPCR to measure microRNA-7 expression in A549 non-small cell lung cancer cells treated with metformin. We used CCK8, cell scratch, and Transwell assays to test the growth, migration, and invasion of A549 cells. Western blotting was used to measure the expression level of relevant proteins in A549 cells. We found that microRNA-7 was dramatically upregulated by metformin via AMPK in a dose- and time-dependent manner. Both metformin and microRNA-7 mimic reduced A549 cell growth, migration, and invasion. Metformin downregulated the levels of p-NF-κB p65, p-Erk1/2, p-AKT, and p-mTOR proteins. The treatment with the microRNA-7 mimic had the same result. The decrease of these proteins caused the inhibition of A549 cell growth, migration, and invasion. Our discovery revealed that metformin, via increasing the expression of microRNA-7 mediated by AMPK, regulates the AKT/mTOR, MAPK/Erk, and NF-κB signaling pathways, thereby suppressing A549 cell growth, migration, and invasion.