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Despite the remarkable progression in colon cancer treatment in recent years, the pathological mechanism underlying this disease remains unclear. This study aimed to discuss the potential of luteolin in the treatment of colon cancer, from the perspective of traditional Chinese medicine, with a particular focus on the tumor microenvironment.Reverse transcription quantitative polymerase chain reaction and western blot were used to analyze the effects of luteolin on interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3)/Phospho-STAT3. Enzyme-linked immunosorbent assay was used to analyze the protein secretion of IL-6. Proliferation and transwell assays were used to analyze the growth and migration of luteolin and IL-6 in colon cancer cells, respectively.Stimulation with lipopolysaccharides (LPS) promoted the M1 polarization of macrophages and increased the expression and secretion of IL-6. However, the presence of luteolin inhibited the effects of LPS. M1 polarization increased the proliferation rate, migration and invasion ability, and phosphorylation of STAT3 in colon cancer cells (SW620 and SW480). Luteolin inhibited these effects by reducing M1 polarization. To confirm that the action of luteolin is mediated by IL-6/STAT3 signaling, we treated SW620 and SW480 cells with recombinant IL-6 protein and anti-IL-6 antibody. IL-6 was observed to promote cell proliferation, enhance migration and invasion, and increase STAT3 phosphorylation. The opposite effect was observed with the anti-IL-6 antibody. In addition, IL-6 promoted LPS-induced M1 polarization, while the anti-IL-6 antibody enhanced the decrease in luteolin-induced M1 polarization.Luteolin suppressed the growth and migration/invasion potential of colon cancer cells by inhibiting the IL-6/STAT3 signaling pathway.

Purpose: To investigate the effect of curcumin on spinal cord injury (SCI) in a rat model. Methods: SCI was induced in the rats using mid thoracic spinal cord compression, after which curcumin was injected intraperitoneally. Western blotting was used for assay of expressions of apoptotic proteins, viz, IL-1β, NF-κB p65, TLR4, TNF-α, LC3, Bax and Bcl-2. Malondialdehyde (MDA) and myeloperoxidase were measured using standard methods. Neuronal loss in spinal cord tissues was determined with TUNEL staining and NeuN labelling. Results: Curcumin treatment significantly (p < 0.05) suppressed SCI-mediated upregulation of myeloperoxidase activity and increase in MDA level in rat spinal cord. The reduction of glutathione (GSH) and superoxide dismutase (SOD) activities in the spinal cord of SCI rats were suppressed by curcumin treatment. Curcumin treatment also led to a significant (p < 0.02) increase in the proportion of NeuN positive cells and marked reduction in TUNEL positive cells, but it decreased caspase-3 in the spinal cord tissues of SCI rats. Moreover, curcumin reversed the effect of SCI on protein expressions of Bax and Bcl 2 in a dose-based manner. There was marked curcumin-induced decline in CD11b and GFAP levels in the spinal cord tissues of the SCI rats. Conclusion: These results demonstrate that curcumin protects rats against SCI via inhibition of oxidative stress-mediated neuronal apoptosis. Therefore, curcumin may be useful for the development of an effective treatment for spinal cord injury.

Bus bunching is of particular concern and undesirable for both operators and passengers in high-frequency transit. In contrast to existing control methods, this paper proposes a novel control policy, namely, providing real-time bus crowding information (BCI) for passengers. It is believed that passengers would spontaneously distribute more evenly among buses and help to prevent bus bunching with the provision of BCI accompanying arrival time information due to the following mechanism. A proportion of passengers would be likely to wait a few more minutes for the next bus when the current bus is crowded and the next bus is more comfortable, and the boarding times of these passengers would make the next bus dwell longer and increase its headway from the previous bus. We formulate bus motion models incorporating passenger boarding choice under BCI to realize the policy in simulation experiments. The results demonstrate that the policy can reduce operation instability by approximately 20% in terms of bus headway and single-trip time. In addition, this policy can significantly reduce the in-vehicle crowdedness experienced by passengers by up to 25% at the cost of small increases in the mean journey time in some cases. The simulation experiments on a holding-controlled route also indicate that the proposed policy is able to coordinate with holding well. A sensitivity analysis further confirms that the policy’s performance is robust even if the passengers have low inclinations to choose the next bus. The policy of providing BCI in this paper is especially effective for bus routes with high passenger demand and may have great application potential in practice.

As the population worldwide continues to age, providing improved mobility services for older people becomes increasingly crucial. In recent years, the maturation of bike sharing has led older people to progressively incorporate it into their everyday lives. In this study, station-based bike sharing (SBBS) and dockless bike sharing (DBS) are investigated in relation to older population mobility. This research relies on the fusion of multiple data sources, including SBBS and DBS trip records, point of interest (POI), and meteorological conditions in Nanjing, China. A zero-inflated negative binomial regression model is used to compare the travel behaviors among various age groups with the exposure variable. SBBS outperforms DBS in relation to age equity, while diverse travel behavior patterns are exhibited between the age groups. Although younger users are the majority of users, older users travel more frequently than younger users in bike sharing services. Also, older users are more likely to use shared bikes near the religious and health POIs, as well as in higher population density areas. This study provides beneficial insights into the transport equity and service improvement of bike sharing systems.

Integration between bike sharing and rail transit provides users with a more flexible travel pattern in an effort to address the “first/last mile” problem. This study aims to examine the determinan...

Dockless bike-sharing (DBS) is a novel and prevalent bike-sharing system without stations or docks. DBS has the advantages of convenience and real-time positioning, whereas it brings about some problems such as bike over-supply, disordered parking, and inefficient rebalancing. Forecasting usage and bike distribution are critical in the rebalancing operation for maintaining DBS inventory. By dividing the virtual stations through K-means clustering and processing the four-week Mobike journey data of Nanjing, China, the data of usage and bike count in the 4000 virtual stations are identified. Random forest (RF) is developed to predict the real-time passenger departure, passenger arrival and bike count in the virtual stations. The operation analyses indicate that there is a positive correlation between bike count and usage. RF provides accurate predictions of usage and bike distribution, and almost outperforms five benchmark methods. Forecasting bike distribution is more challenging than forecasting usage because of the volatility of many factors. The results also suggest that bike distribution forecasting based on the usage gap prediction is better than that based on the departure and arrival prediction. This study can help DBS companies in dynamically rebalancing bikes from over-supply regions to over-demand regions in a better way.

Osteosarcoma (OS) is a common primary malignant bone tumor around the world. It has been reported that long noncoding RNAs (lncRNAs) take part in diverse pathological processes of OS; however, the mechanism remains unknown. This study aimed to uncover the profile of lncRNA small nucleolar RNA host gene 15 (SNHG15), its biological function, and its potential involvement in the mechanism of OS progression in vitro and in vivo. The expression of SNHG15 and TRAF4 was promoted in OS tissues opposite for that of miR-346. The silencing of SNHG15 limited the proliferation, invasion, and enhanced apoptosis of SaoS2 and HOS cells. Moreover, the putative binding sites between miR-346 and SNHG15 or TRAF4 were predicted by starBase and Targetscan software online, individually. Also, miR-346 deletion reversed the positive effects of SNHG15 elimination on proliferation, apoptosis, and invasion in cells. In addition, the upregulation of TRAF4 disrupted the biofunctional results from miR-346 promotion subsequently. Finally, SNHG15 knockdown repressed OS tumor growth in a xenograft tumor model. SNHG15 enhanced the progression of OS by regulating the miR-346/TRAF4 axis in vitro and in vivo.

In recent years, there has been a remarkable rebirth of the streetcar in China, with dozens of projects under consideration, in planning and construction, or already completed in cities throughout the country. The development of such a relatively mega-project often raises the question of “why Chinese cities develop their streetcar projects”. Building on insights into streetcar projects materials and in-depth interviews with elite figures, and together with relevant socioeconomic data comparisons, the paper sets out to reveal how the resurgence of the streetcar was facilitated and motivated, and why such urban mega-projects are so attractive to cities, and to further derive lessons to better inform policymakers, planners, and researchers in proposing, planning and implementing streetcars in China. Our findings revealed five major themes to motivate streetcars development in China, which unpacked the answer to the question into five aspects: rapid urbanization, supportive policy environment, less-restrictive approval mechanisms, goal-seeking for streetcar development, and potential inter-city competition. A discussion of these themes in the Chinese context leads us to the conclusion that the process of proposing, promoting, and approving streetcar projects is not only dependent on its expected achievements bring to the region but very much on the economic–political reasons and inter-city competition.

Study Design.In vitro laboratory studies.Objectives.To explore the effect of chondrocell-derived exosomes on intervertebral disc degeneration, and provide a new idea for IDD treatment.Summary of Background Data.The research of exosomes and their regenerative effects have been verified in the research of repair in other tissues and organs at our country and abroad, including osteoarthritis, cardiovascular disease, lung injury, fracture healing, central nervous system disease, cancer and other diseases treatment [1] . The aim of this study was to investigate whether exosomes derived from endplate cells could inhibit the degeneration of endplate and play an important role in the prevention and treatment of disc degeneration.Methods.EPCs-Exos derived from endplate chondrocytes were prepared and identified by Nanoparticle tracking analyzer, transmission electron microscope, and immunoblotting to detect surface markers, it was confirmed by immunofluorescence assay that it could be ingested by nucleus pulposus cells. The degeneration of cartilage endplates was evaluated by detecting the contents of Aggrecan, COL 1A, COL 2A and RNA by RT-PCR and WB.Results.EPCs-Exos can be ingested by nucleus pulposus cells and up-regulate the expression of Aggrecan, COL 2A and their mRNA, down-regulate the expression of COL 1A and their mRNA. Conclusion.EPCS-Exo can further inhibit the degeneration of intervertebral disc by acting on nucleus pulposus cells and thus the degeneration of cartilage endplate.

Objective. The safety and efficacy of Tripterygium glycosides (TG) were assessed for ankylosing spondylitis (AS) in accordance with the existing literatures. Materials and Methods. Electronic literature was searched from Chinese VIP databases, Cochrane Library, Chinese Biomedical Literature Database, Wanfang Web of Science, EMBASE, Chinese National Knowledge Infrastructure, and the PubMed for the studies with the publication from the beginning to December 2021. Randomized controlled trials (RCTs) were included only. The major variables of result comprised erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Spinal Pain Visual Analog Score (SP-VAS), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Moreover, the secondary variables of result covered the overall clinical effective rate following the adverse drug reaction (ADR). We carried out the meta-analysis with the use of STATA 12.0 and RevMan 5.3. We used GRADE pro3.6.1 software to assess the quality of evidence. Results. In general, we covered 15 randomized controlled trials with the focus of 1186 patients. As proven by our meta-analysis, TG as adjuvant therapy or monotherapy decreased the BASDAI, BASFI, SP-VAS, serum CRP, and ESR than control in patients suffering from AS. Additionally, TG treatment visibly improved the overall effective rate in AS. Nevertheless, TG was not found to significantly increase the rate of ADR in contrast to the control. Conclusion. As indicated by our result, TG may be an option to treat AS. In this paper, we recommended strict trials with high quality and large samples sizes for confirming the finding here.

Background Osteosarcoma (OS) is a very aggressive cancer. Nevertheless, how circular RNA (circRNA) contributes to OS progression remains unclear. Here, we aimed to research the functions of circMMP9 in OS progression. Methods Gene expression was determined via qRT-PCR. siRNA was used to knock down circMMP9. Proliferation was analyzed using CCK8 and colony formation assays. Migration and invasion were measured using Transwell assay. Results circMMP9 was overexpressed in cancer tissues. Overexpressed circMMP9 was correlated with advanced tumor stage and predicted poor prognosis. circMMP9 knockdown exhibited a tumor-suppressive phenotype via suppressing proliferation, migration and invasion. Besides, decreased circMMP9 level promoted OS cellular apoptosis. Mechanistically, circMMP9 was shown to be located in the cytoplasm and sponge miR-1265. Furthermore, miR-1265 directly targeted CHI3L1. CHI3L1 levels were modulated by circMMP9/miR-1265 axis. Rescue experiments indicated that circMMP9 contributes to OS development through the miR-1265/CHI3L1 pathway. Conclusion Our findings provide a novel insight about how circRNA regulates OS progression.

The application of travel demand models to transportation planning has triggered great interests in issues that potentially improve the accuracy of model forecasts. These forecasts, however, are su...

China has been witnessing prominent demographic ageing because of its sustained low fertility (one-child policy) and mortality rates. In 2017, nearly one in four elderly adults in the world live in China. The rapid increase of the elderly population is supposed to dramatically influence the urban and transportation system. Active travel plays an important role for the ageing Chinese population to sustain their mobility and wellbeing. To provide suitable policy implications for age-friendly travel environments in China, this study investigates how the built environment affects active travel behavior. Particularly, we explore the influences of built environment on daily active travel frequency and time expenditure while taking into account travel attitudes. A zero-inflated ordered probit model and a Cox proportional hazards model are respectively estimated based on the Nanjing Travel Survey data. Results show that the social and cultural contexts exert pronounced impacts on the travel pattern of Chinese older people. Specifically, it is found that the living pattern of co-residence, and the proximity to market, park/square, and chess/card room are influential in shaping active travel patterns. In addition, the built environment shows larger effects on the active travel behavior of older adults than on that of young people. Attitudes towards active travel are not significant in explaining the senior's travel behavior, indicating limited self-selection effects. The findings will offer insights to establish effective and appropriate land use strategies and public facility distribution for the elderly during the Chinese urban renewal process.

The analysis of travel mode choice is important in transportation planning and policy-making in order to understand and forecast travel demands. Research in the field of machine learning has been exploring the use of random forest as a framework within which many traffic and transport problems can be investigated. The random forest (RF) is a powerful method for constructing an ensemble of random decision trees. It de-correlates the decision trees in the ensemble via randomization that leads to an improvement of forecasting and reduces the variance when averaged over the trees. However, the usefulness of RF for travel mode choice behavior remains largely unexplored. This paper proposes a robust random forest method to analyze travel mode choices for examining the prediction capability and model interpretability. Using the travel diary data from Nanjing, China in 2013, enriched with variables on the built environment, the effects of different model parameters on the prediction performance are investigated. The comparison results show that the random forest method performs significantly better in travel mode choice prediction for higher accuracy and less computation cost. In addition, the proposed method estimates the relative importance of explanatory variables and how they relate to mode choices. This is fundamental for a better understanding and effective modeling of people’s travel behavior.

Health care accessibility is a vital indicator for evaluating areas where there are medical shortages. However, due to the lack of population data with a satisfactory spatial resolution, efforts to accurately measure health care accessibility among older individuals have been hampered to some extent. To address this issue, we attempt to measure accessibility to health care services for older bus passengers in Nanjing, China, using a finer spatial resolution. More specifically, based on one month's worth of bus smart card data, a framework for identifying the home stations (i.e., a passenger's preferred station near their residence) of older passengers is developed to measure the aggregate demand at the bus stop scale. On this basis, a measurement that integrates the Gaussian two-step floating catchment area (2SFCA) and the adjusted 2SFCA methods (referred to as the adjusted Gaussian 2SFCA method) is proposed to measure accessibility to health care services for older people. The results show that: (1) almost all home stations experience inflated demand, especially those located in the suburbs; (2) despite abundant health care resources, home stations in urban districts are rarely identified as high accessibility stations, due to high demand densities among the older population; and (3) more attention should be paid to two types of home stations – those with a medical institution and those with bed shortages, respectively. The first type is predominantly distributed in the periphery of the city, in the suburbs where the travel time required to access the nearest health care service by bus is longer. The second type is mostly located in the outskirts of urban districts and in the central area of one suburb. These findings could help policy makers to implement more appropriate measures to design and reallocate health care resources.

Dockless bike sharing (DBS), as an emerging bike sharing scheme, effectively promotes active travel and improves the mobility of users. Travel behavior analysis of DBS users is a key basis of service improvement, and the data sources include user surveys and trip records. User surveys are widely applied but have the drawback of perceptual errors. Thus, there is a compelling need for exploring travel behavior using automatically-collected trip records. This study examines DBS users' travel frequency and purpose with five semi-annual user surveys and trip record data in Nanjing, China. User surveys reflect user perception of travel behavior, while trip records can be used to calculate actual travel frequency and infer travel purpose. The results show that perceptual travel frequency based on user surveys has a central tendency, and actual travel frequency based on trip records follows a heavy-tailed distribution. Older people tend to underestimate their travel frequency, but other age groups tend to overestimate their frequency. In addition, a dockless bike sharing's travel purpose inferring (DBS-TPI) model is proposed to infer the travel purpose based on trip record data and points of interest data. The DBS-TPI model is reliable and transferable under different scenarios, which could complement user surveys. This study provides insights into improving data collection for better understanding of travel behaviors among DBS users.

This paper proposes a continuum approximation (CA) modeling framework to optimize the hybrid transit network designed with grids in the central district and hub-and-spoke structure in the periphery. Two CA models are formulated incorporating the local route service and the short-turn strategy respectively. The transit network configuration is optimized through minimizing the objective functions, which consider costs pertinent to passengers and operating agency. The decision variables include service boundary, spacings and headways of the regular service and the complementary services. Numerical experiments show that the performances of CA models with different complementary services are quite distinct under various demand scenarios.

In frequently serviced bus routes passengers are more concerned about bus headway regularity than actual punctuality to the schedule. The buses tend to bunch naturally partly because of the partici...

Bus stops provide accessibility to public transit service, whereas they also influence the efficiency of mobility due to the extra dwell time. The decision of bus stop locations is a tradeoff between access coverage and mobility. This paper formulates a biobjective optimization model of bus stop placement problem at the network level. Two objectives are pertinent to the improvement of mobility: minimization of total dwell time at stops and minimization of total number of bus stops. Access coverage is constrained to ensure a certain level of accessibility. The issue of stop congestion and its effect on road traffic flow is also considered in the model. The model is applied to a case study of the bus network in urban areas of Yancheng, China. The results show that the proposed model can be efficiently solved by CPLEX to obtain Pareto optimal solutions for real-case problems.

Smart card (SC) data has become one of the major data sources for transit passengers’ behavior analysis, network modeling, and control optimization. Origin–destination (O–D) estimation has been recognized as a requisite step before utilizing the smart card data to investigate transit passengers’ spatiotemporal dynamics or conduct other SC data-based transit modeling. In the recent decade, the extant literature has proposed various trip-chain-based methods for transit O-D estimation using SC data. However, one problem of the conventional trip-chaining estimation approach has been noticed but not paid enough attention to: O-D estimation of single transactions cannot be conducted since the trip-chain method generally requires at least two trip records per day to proceed with. Such a flaw in the classic trip-chain approach might lead to a considerable amount of data loss and inaccurate O-D estimation. This paper improved the existing trip-chain O-D estimation method by introducing a new framework based on the Minimum Entropy Rate (MER) criterion. The proposed MER-based method adopts a similar mechanism of noise reduction in information theory. The basic idea of our approach is to infer the alighting location of single trips using alternative stops that preserve passengers’ travel regularity exhibiting in their mobility sequences. Our enhanced approach can estimate alighting stops for single trips with decent accuracy, thus preventing a potential massive data loss. Moreover, the study also provides an in-depth insight into the relationship between entropy rates estimated using trip sequences and passengers’ travel regularity. The estimation results can further benefit future transit studies with reliable data sources.

Introduction Coronavirus disease 2019 (COVID-19) has triggered a worldwide outbreak of pandemic, and transportation services have played a key role in coronavirus transmission. Although not crowded in a confined space like a bus or a metro car, bike-sharing users are exposed to the bike surface and take the transmission risk. During the COVID-19 pandemic, how to meet user demand and avoid virus spreading has become an important issue for bike-sharing. Methods Based on the trip data of bike-sharing in Nanjing, China, this study analyzes the travel demand and operation management before and after the pandemic outbreak from the perspectives of stations, users, and bikes. Semi-logarithmic difference-in-differences model, visualization methods, and statistic indexes are applied to explore the transportation service and risk prevention of bike-sharing during the pandemic. Results Pandemic control strategies sharply reduced user demand, and commuting trips decreased more significantly. Some stations around health and religious places become more important. Men and older adults may be more dependent on bike-sharing systems. The declined trips reduce user contacts and transmission risk. Central urban areas have more user close contacts and higher transmission risk than suburban areas. Besides, a new concept of user distancing is proposed to decrease transmission risk and the number of idle bikes. Conclusions This paper is the first research focusing on both user demand and transmission risk of bike-sharing during the COVID-19 pandemic. This study evaluates the mobility role of bike-sharing during the COVID-19 pandemic, and also provides insights into curbing the viral transmission within the city.

Schizophrenic patients tend to have reduced incidence of some cancers due to the treatment of antipsychotic drugs with antitumor effects, such as chlorpromazine and trifluoperazine (TFP). Forkhead Box O1 (FOXO1) as tumor suppressor in many malignancies is often inactivated by nuclear export, which could be inhibited by TFP. However, the antitumor efficiency of TFP and related role of FOXO1 in hepatocellular carcinoma (HCC) are unclear. Thus, two HCC cell lines SMMC-7721 and Bel-7402 were treated with different concentrations of TFP and the IC50 was determined. We found that TFP could inhibit the vitality of two cell lines and induce cell cycle arrest at G0/G1. Meanwhile, the apoptosis was also increased and the ability of migration or invasion was found to be impaired by TFP. Interestingly, TFP reversed the cytoplasmic localization of FOXO1 to nuclear and increased its expression in nuclear, and increased the ratio of Bax/Bcl-2. However, knockdown of FOXO1 significantly abrogated the TFP-induced apoptosis by decreasing the Bcl-2 expression [corrected]. Furthermore, we found that TFP in vivo could effectively restrict the angiogenesis and tumor growth with reduced expression of VEGF, Bcl-2, and PCNA, and increased the nuclear localization of FOXO1, which indicated its antitumor role in HCC.

Low-income commuters have distinct activity-travel characteristics from non-low-income commuters. This study examines low-income commuters’ activity-travel pattern for a better understanding the me...

In China, low-income commuters are usually concentrated in peripheral settlements outside downtown areas, where travel services are inadequately provided. These commuters are dependent on fewer travel options, considering their affordability. Based on the recognition that public transit is an important mode to enhance low-income commuters’ travel mobility, a comprehensive attitude-based market segmentation analysis was performed to identify distinct market segments to best serve the needs of each segment and to develop plans to increase transit usage. First, a detailed household survey was conducted in Fushun, China, to obtain commuters’ attitudes toward daily travel. Then, factor analysis was utilized to explore latent attitudinal factors. The structural equation modeling investigated the correlations between attitudes and public transit usage. The k-means clustering was then employed to partition the transit market into several subgroups. Finally, five segments of transit market with distinct attitudes were identified by three dividing variables, namely, the desire for comfort, the need for reliability, and environmental awareness. Low-income commuters in the same segment share homogeneous travel preferences while those in other segments possess different attitudes. The attitudinal characteristics, socioeconomic profile, and mode choice behavior in each segment were examined and discussed. Policies that best meet the needs of each submarket were proposed. These transit-related strategies included building a reliable operation environment, improving the level of service of existing facilities, implementing demand-response transit services, and providing public propaganda and education toward environmental protection.

Low-income residents can depend on fewer travel options and have restricted mobility. This paper analyzes low-income commuters’ mode choice behavior by using data from an activity-based travel survey in Fushun, China. An integrated choice and latent variable model is presented. The model uses the following latent attitudes: comfort, convenience, reliability, flexibility, safety, and environmental preferences. The inclusion of attitudes captures unobserved heterogeneity of the choice process with a better understanding of travel demands. Postestimation of the integrated model is applied to assess the responsiveness of preferences for various transportation modes to changes in policy-relevant variables. This assessment is done by calculating the elasticity and marginal effects of choice probabilities for the relevant attributes of travel preferences. The analysis indicates that individuals with high comfort preferences care more about walking environment, and they need solutions to enhance their walking experience. However, travelers preferring reliability are more likely to travel by public transit, and measures to inform commuters of real-time bus operation information were proposed. Commuters who emphasize environmental preference are more apt to cycle; therefore, probike strategies are recommended. Results of the analysis indicate that different actions should be taken to serve different preferences. The findings should be useful information for policy makers and transportation planners wanting to improve low-income commuters’ travel quality.

Osteosarcoma (OS) is a common primary malignant bone tumor around the world. It has been reported that long noncoding RNAs (lncRNAs) take part in diverse pathological processes of OS; however, the mechanism remains unknown. This study aimed to uncover the profile of lncRNA small nucleolar RNA host gene 15 (SNHG15), its biological function, and its potential involvement in the mechanism of OS progression in vitro and in vivo. The expression of SNHG15 and TRAF4 was promoted in OS tissues opposite for that of miR-346. The silencing of SNHG15 limited the proliferation, invasion, and enhanced apoptosis of SaoS2 and HOS cells. Moreover, the putative binding sites between miR-346 and SNHG15 or TRAF4 were predicted by starBase and Targetscan software online, individually. Also, miR-346 deletion reversed the positive effects of SNHG15 elimination on proliferation, apoptosis, and invasion in cells. In addition, the upregulation of TRAF4 disrupted the biofunctional results from miR-346 promotion subsequently. Finally, SNHG15 knockdown repressed OS tumor growth in a xenograft tumor model. SNHG15 enhanced the progression of OS by regulating the miR-346/TRAF4 axis in vitro and in vivo.

Background Osteosarcoma (OS) is a very aggressive cancer. Nevertheless, how circular RNA (circRNA) contributes to OS progression remains unclear. Here, we aimed to research the functions of circMMP9 in OS progression. Methods Gene expression was determined via qRT-PCR. siRNA was used to knock down circMMP9. Proliferation was analyzed using CCK8 and colony formation assays. Migration and invasion were measured using Transwell assay. Results circMMP9 was overexpressed in cancer tissues. Overexpressed circMMP9 was correlated with advanced tumor stage and predicted poor prognosis. circMMP9 knockdown exhibited a tumor-suppressive phenotype via suppressing proliferation, migration and invasion. Besides, decreased circMMP9 level promoted OS cellular apoptosis. Mechanistically, circMMP9 was shown to be located in the cytoplasm and sponge miR-1265. Furthermore, miR-1265 directly targeted CHI3L1. CHI3L1 levels were modulated by circMMP9/miR-1265 axis. Rescue experiments indicated that circMMP9 contributes to OS development through the miR-1265/CHI3L1 pathway. Conclusion Our findings provide a novel insight about how circRNA regulates OS progression.