Tumors In China Research Articles

The Effect of Magnetic Resonance Imaging Based Radiomics Models in Discriminating stage I-II and III-IVa Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a common tumor in China. Accurate stages of NPC are crucial for treatment. We therefore aim to develop radiomics models for discriminating early-stage (I-II) and advanced-stage (III-IVa) NPC based on MR images. 329 NPC patients were enrolled and randomly divided into a training cohort (n = 229) and a validation cohort (n = 100). Features were extracted based on axial contrast-enhanced T1-weighted images (CE-T1WI), T1WI, and T2-weighted images (T2WI). Least absolute shrinkage and selection operator (LASSO) was used to build radiomics signatures. Seven radiomics models were constructed with logistic regression. The AUC value was used to assess classification performance. The DeLong test was used to compare the AUCs of different radiomics models and visual assessment. Models A, B, C, D, E, F, and G were constructed with 13, 9, 7, 9, 10, 7, and 6 features, respectively. All radiomics models showed better classification performance than that of visual assessment. Model A (CE-T1WI + T1WI + T2WI) showed the best classification performance (AUC: 0.847) in the training cohort. CE-T1WI showed the greatest significance for staging NPC. Radiomics models can effectively distinguish early-stage from advanced-stage NPC patients, and Model A (CE-T1WI + T1WI + T2WI) showed the best classification performance.

Academic progress research on the prevention of surgical incision scar during surgical treatment of benign breast tumors

Objective: This article summarizes the progress of surgical treatment of benign breast tumors and the prevention of incision scars during surgery. Methods: In this paper, the relevant research literature on the surgical treatment of benign breast tumors in China and the world was consulted, analyzed, and summarized. Conclusion: Many methods in this article can be used for scar treatment during the recovery period of surgery, and the success rate of these methods varies with different body constitutions. Since no single treatment modality is ideal for scarring, clinical management varies from individual to individual. The point of view of this article is that based on the basic principles of wound care, doctors need to be familiar with the problems that should be paid attention to in the process, from incision to scar, and handle the details of the operation preparation stage, operation process, and operation recovery period, and strive for ideal wound surface during the operation recovery period.

Advantages of Combined Chinese and Western Medicine in Treating Liver Cancer

Primary liver cancer (abbreviated as hepatocellular carcinoma) is a malignant tumor occurring from intrahepatic bile duct cells or hepatocytes, which is one of the common malignant tumors in China. Early stage liver cancer is mainly treated by surgery, interventional therapy, local ablation therapy, immunotherapy, etc. However, most liver cancers are already in the middle and late stages when diagnosed, and western medical treatment has certain limitations; but at the same time, Chinese medicine treatment has certain advantages, which can improve postoperative status, enhance patients' immunity, improve patients' systemic symptoms, and help improve life quality. In this paper, we review the advantages of Western medical treatment combined with TCM in the treatment of primary hepatocellular carcinoma.

The Krüppel-like factor 6 represses proliferation and invasion ofcutaneous malignant melanoma.

Cutaneous carcinoma is one ofthemost common neoplasm tumors in theWest. Its incidence rate is one ofthefastest growing tumors in China. TheKrüppel-like factor 6 (KLF6) is alatent tumor suppressor. Decreased KLF6 is related to theoccurrence and progression ofmany cancers in human. Our previous studies have demonstrated that KLF6 was down-regulation in cutaneous malignant melanoma (CMM), and was significant correlated with ulcer, lymph node metastasis and clinical stage, suggesting that KLF6 loss is expected to become abiological indicator ofpoor prognosis in CMM patients. In this research, we would further study thefeatures ofKLF6 in themalignant progression ofCMM. Theexpression ofKLF6 was up-regulated by lentivirus infection containing KLF6, and short hairpin RNA (shRNA) was used for knockdown ofKLF6 in CMM cells. Western blot, RT-qpcr, CCK8 assay, transwell migration assays, wound healing assay and flow cytometry were used to test therole ofKLF6 in theCMM. We found that reduced expression ofKLF6 significantly enhanced proliferation, migration and invasion. Moreover, KLF6 induced CMM cell apoptosis and G1 cycle arrest. Thedecreased KLF6 expression is expected to be abiological indicator ofpoor prognosis in CMM patients.

Detection of nasopharyngeal cancer cells using the laser tweezer Raman spectroscopy technology.

Nasopharyngeal cancer (NPC), which arises from the nasopharyngeal epithelial lining, is one of the common malignant otorhinolaryngological tumors in China. Due to its insidious anatomical location and highly invasive and metastatic features, it is challenging to detect NPC at early stages. In this work, a rapid laser tweezer Raman spectroscopic (LTRS) system was built and used to trap and characterize single NPC cells. Using LTRS, high-quality Raman signals of the normal nasopharyngeal cell line (NP69) and NPC cells could be successfully obtained. By analysing the Raman peaks, some unique changes were found in components, such as DNA, amide I and amide III, in NPC cells compared with normal cells. In addition, we also used a multivariate statistical algorithm to establish a diagnostic model for identifying NPC cells with an accuracy of 90.0%. These results demonstrate that LTRS in combination with the multivariate statistical analysis is a convenient and high-efficiency cell identification technology, providing a novel and rapid methodology for NPC detection at the single cell level.

Upregulation of SCD1 by ErbB2 via LDHA promotes breast cancer cell migration and invasion.

The incidence of breast cancer ranks at the top of female malignant tumors in China. Metastasis remains the main cause of death among breast cancer patients. The overexpression of ErbB2 is closely related to the metastasis and poor prognosis of breast cancer patients. Therefore, ErbB2 is an important clinical therapeutic target of breast cancer. However, the molecular mechanism of ErbB2 promoting breast cancer metastasis has not been studied clearly. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in catalyzing the conversion of saturated fatty acids (SFAs) into monounsaturated fatty acids (MUFAs). SCD1 is overexpressed in breast cancer, and its overexpression is an indicator of poor prognosis in breast cancer patients. However, the role of SCD1 in ErbB2-overexpressing breast cancer metastasis has not been reported. In this study, we investigated the role of SCD1 in the migration and invasion of ErbB2-overexpressing breast cancer cells and its molecular mechanism. First, we demonstrated that ErbB2 upregulates the expression of SCD1. Second, we found that SCD1 and its catalytic product oleic acid played crucial roles in migration and invasion of ErbB2-overexpressing breast cancer cells. Finally, we found that in breast cancer cells, ErbB2 upregulated SCD1 through lactate dehydrogenase A (LDHA). To sum up, upregulation of SCD1 by ErbB2 via LDHA promotes the migration and invasion of breast cancer cells.

Targeting rare tumors: new focus for clinical research in China.

Rare tumor has a huge unmet medical need without standard regimens, calling for novel therapeutic interventions. The National Cancer Center of China identified a threshold of incidence for rare tumor as 2.5/100,000, based on the characteristics of Chinese population. Molecular profiles for rare tumor patients in China further provided prospects for precise and individualized targeted treatment. An ongoing phase II clinical trial, the PLATFORM study, is the first trial tailored for rare solid tumors in China, featured by molecule-guided therapeutics. With the promulgation of supportive policies to encourage the development of innovative drugs for rare tumors in China, opportunities will be provided for these patients and the gap will be filled in the treatment of rare tumors.

Cordycepin Inhibits the Growth of Hepatocellular Carcinoma by Regulating the Pathway of Aerobic Glycolysis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, with a high incidence and mortality rate. Glucose metabolism reprogramming is a major characteristic of tumor cells. Increasing evidence indicates that aerobic glycolysis is associated with tumor growth and insensitivity to chemotherapy. Cordycepin inhibits the growth of HCC cells, but the mechanism is yet to be elucidated. Herein, in vitro and in vivo methods were utilized to investigate the cordycepin-inhibited growth of HCC by regulating the metabolic pathway of aerobic glycolysis. In vitro analyses using colony formation and flow cytometry revealed that cordycepin inhibits HCC cells' proliferation and promotes apoptosis. In addition, cordycepin reduced the production of lactic acid and pyruvate, reduced the uptake of glucose, and decreased the extracellular acidification in HCC cells. Specifically, cordycepin inhibited the expression of HK2, LDHA, and PKM2 in aerobic glycolysis via the AMPK-Akt pathway. Taken together, these findings revealed that cordycepin reduces the tumor energy supply and decreases lactic acid production, thereby inhibiting the growth of HCC cells by regulating the metabolic pathway of aerobic glycolysis. These findings might provide novel insights into the mechanisms underlying cordycepin-mediated inhibition of tumor growth as well as a new treatment for HCC.

Triptonoterpene, a Natural Product from Celastrus orbiculatus Thunb, Has Biological Activity against the Metastasis of Gastric Cancer Cells.

Cancer is one of the greatest threats to human health. Gastric cancer (GC) is the fifth most common malignant tumor in the world. Invasion and metastasis are the major difficulties in the treatment of GC. Herbal medicines and their extracts have a lengthy history of being used to treat tumors in China. The anti-tumoral effects of the natural products derived from herbs have received a great deal of attention. Our previous studies have shown that the traditional Chinese herb Celastrus orbiculatus Thunb extract (COE) can inhibit the invasion and metastasis of GC cells, but the specific anti-cancer components of COE are still unclear. Dozens of natural products from COE have been isolated and identified by HPLC spectroscopy in our previous experiments. Triptonoterpene is one of the active ingredients in COE. In this study, we focused on revealing whether Triptonoterpene has an excellent anti-GC effect and can be used as an effective component of Celastrus orbiculatus Thunb in the treatment of tumors. We first observed that Triptonoterpene reduces GC cell proliferation through CCK-8 assays and colony formation experiments. The cell adhesion assays have shown that Triptonoterpene inhibits adhesion between cells and the cell matrix during tumor invasion. In addition, the cell migration assay has shown that Triptonoterpene inhibits the invasion and migration of GC cells. The high-connotation cell dynamic tracking experiment has also shown the same results. The effects of Triptonoterpene on epidermal mesenchymal transition (EMT)-related and matrix metalloproteinases (MMPs)-related proteins in gastric cancer cells were detected by Western blots. We found that Triptonoterpene could significantly inhibit the changes in EMT-related and invasion and metastasis-related proteins. Altogether, these results suggest that Triptonoterpene is capable of inhibiting the migration and invasion of GC cells. Triptonoterpene, as a natural product from Celastrus orbiculatus Thunb, has significant anti-gastric cancer effects, and is likely to be one of the major equivalent components of Celastrus orbiculatus Thunb.

Patients with non-functional metastatic G2 pancreatic neuroendocrine tumor benefit from palliative surgery: A 20-year single-center retrospective analysis.

Pancreatic neuroendocrine tumor (pNET) is the most common subset (31.5%) of gastroenteropancreatic neuroendocrine tumor in China. Based on real-world data from a single center, the present study aimed to evaluate the influence of clinical characteristics, medical treatment and surgery on the survival of non-functional metastatic G2 pNET. In total, 114 metastatic non-functional G2 pNET patients, who were treated and followed up in the Department of Medical Oncology, Peking Union Medical College Hospital (PUMCH) from 2001 until 2019, were analyzed retrospectively. The primary endpoint, overall survival (OS), was calculated from the date of diagnosis to the date of death. The second endpoint, progression-free survival (PFS), was calculated from the date of diagnosis to the date of disease progression. Statistical data were analyzed to evaluate the effects of a clinical characteristic, medical treatment and surgery on OS and PFS. Sixty-nine (60.5%) patients were male and 87 (76.3%) were aged < 60 years. The liver was the most common metastatic organ, with a total of 84 cases (73.7%). With respect to surgery, 32 (28.1%) patients underwentradical surgery and 37 (32.5%) underwent palliative surgery. Survival analysis showed that the 5-year and 10-year survival rates were 79.36% and 70.0%, respectively. Univariate and multivariate Cox regression analyses suggested that both radical (p < .001/.003) and palliative surgery (p < .001/.002) significantly prolonged OS, as revealed by the Kaplan-Meier test (p < .001). Subgroup analysis showed that palliative resection also significantly improves the prognosis in patients with multiple liver metastases. However, the first-line systemic anti-tumor therapy option showed no statistical differences in the present study. Overall, patients with non-functional metastatic G2 pNET receiving palliative or radical surgery demonstrated significantly better survival. Prospective clinical trials are suggested to validate our findings.

Novel long noncoding RNA LINC02820 augments TNF signaling pathway to remodel cytoskeleton and potentiate metastasis in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in China. However, there are no targets to treat ESCC because the molecular mechanism behind the cancer is still unclear. Here, we found a novel long noncoding RNA LINC02820 was upregulated in ESCC and associated with the ESCC clinicopathological stage. Through a series of functional experiments, we observed that LINC02820 only promoted the migration and invasion capabilities of ESCC cell lines. Mechanically, we found that LINC02820 may affect the cytoskeletal remodeling, interact with splice factor 3B subunit 3 (SF3B3), and cooperate with TNFα to amplify the NF-κB signaling pathway, which can lead to ESCC metastasis. Overall, our findings revealed that LINC02820 is a potential biomarker and therapeutic target for the diagnosis and treatment of ESCC.

HPV Vaccine Hesitancy and Influencing Factors among University Students in China: A Cross-Sectional Survey Based on the 3Cs Model.

The burden of disease caused by cervical cancer ranked second among female tumors in China. The HPV vaccine has been proven to be a cost-effective measure to prevent cervical cancer, but the vaccination rate remained low to date among university students. This study aimed to understand the status quo of HPV vaccine hesitancy among university students across China during the COVID-19 pandemics and systematically analyze determinants of HPV vaccine hesitancy based on the WHO 3Cs model. Cross-sectional data were collected using an online survey of female university students in four cities across China in June 2022. Multinomial logistic regression was adopted to determine factors influencing vaccine hesitancy based on the 3Cs model with three dimensions, namely complacency, convenience, and confidence. Among 1438 female university students surveyed in this study, 89.7% did not hesitate to vaccinate against HPV, only 8.9% hesitated to some extent, and 1.4% refused to vaccinate. The actual vaccination rate for the HPV vaccine was 34.2%. Based on the 3Cs model, this study found that the trust on the efficacy of vaccines, risk perception of being infected by HPV, price, and distance/time were influencing factors of vaccine hesitancy. Knowledge of the HPV vaccine and sociodemographic characteristics, such as education levels, were also statistically relevant. Therefore, it is recommended that relevant scientific knowledge on cervical cancer and the HPV vaccine should be spread on campus, the vaccination appointment procedure should be simplified, and the affordability of vaccination should be increased through strategic purchasing or providing subsidies, so as to reduce HPV vaccine hesitancy.

Exploring Effectiveness and Safety of Nimotuzumab in Recurrent or Metastatic Cervical Cancer

<h3>Purpose/Objective(s)</h3> Cervical cancer is the sixth most common malignant tumor in China lacks effective and safe treatment, especially in the recurrent or metastatic type. The study explores the effectiveness and safety of nimotuzumab in patients with recurrent or metastatic cervical cancer after failure of the first line of therapy. <h3>Materials/Methods</h3> The patients with recurrent or metastatic cervical cancer after failure of first-line of therapy received nimotuzumab (200mg, weekly, six weeks) at The First Affiliated Hospital of Xi'an Jiaotong University from the year 2019 to 2021 were retrospectively analyzed. The primary endpoint was the objective response rate (ORR). The secondary endpoints were disease control rate response (DCR), the median duration of response (DOR), progression-free survival (PFS), and the overall survival (OS) as well. <h3>Results</h3> A total of 20 eligible patients were analyzed with a median follow-up time of 7.8 months. 14 (70%) of 20 patients received chemotherapy, 5 (25%) of radiotherapy, 1 (5%) of chemoradiotherapy. 5 (25%) patients received paclitaxel plus carboplatin. The CR, ORR, and DCR in all the patients were 10%, 40%, and 60%, respectively. The median duration of response (DOR) was not reached. DOR rate of 6 months was 68.6%. The mPFS was 5.8 months (95 CI%, 3.0-13.4) and the mOS was not reached. Subgroup analysis was also included. ORR and DCR were 42.9%, 57.1%, respectively, in the nimotuzumab-chemotherapy group (n=14). CR, ORR and DCR were 20.0%, 20.0% and 60.0%, respectively, in nimotuzumab-radiotherapy group (n=5). The mPFS was 5.8 (95 CI%, 2.27-.) and 7.5 months (95 CI%, 1.97-12.0) in both groups, respectively. As for the nimotuzumab-chemotherapy group, the patients treated by nimotuzumab-platinum-paclitaxel (n=5) had a better response up to ORR 80% and with the highest overall mPFS 10.1 months (95% CI, 3.4-.). In patients who had failed first-line therapy (n=10) and second/third-line therapies (n=10), the mPFS was 13.4 months (95 CI%, 2.0-.) and 5.6 months (95 CI%, 1.5-12.0). Adverse reactions were mainly limited to grade 1 or 2, and no more serious adverse reactions occurred. <h3>Conclusion</h3> Nimotuzumab showed encouraging efficacy and safety for patients with recurrent or metastatic cervical cancer after failure of first-line of therapy, especially combined with platinum plus paclitaxel.

Meta-analysis of the efficacy and safety of sintilimab for treating advanced non-small cell lung cancer.

Lung cancer is the leading cause of death from malignant tumors in China, and non-small cell lung cancer (NSCLC) accounts for >80% of all types of lung cancer. Novel immunotherapeutic agents targeting programmed death protein-1 (PD-1) and its ligands [programmed death ligands (PD-L)1 and 2] have emerged as important therapeutic measures and trends in the treatment of advanced NSCLC. Sintilimab (trade name, Daboshu) is a humanized IgG4 monoclonal antibody targeting PD-1 that was developed by Innovent Biologics and Eli Lilly and Company. Studies have shown that sintilimab has the characteristics of high affinity, long-lasting stability and an increased target occupancy rate, and that it is a broad-spectrum drug. The present study uses a meta-analysis to evaluate the safety and efficacy of sintilimab in treating advanced NSCLC. The PubMed, Cochrane Library, Embase, Chinese Biomedical Literature, China National Knowledge Infrastructure, VIP Chinese Science and Technology Journal and Wanfang Medical databases were searched from their establishment until October 2021. Randomized controlled trials of patients with NSCLC who were treated with conventional chemotherapy (chemotherapy) plus sintilimab treatment or sintilimab alone, compared with a chemotherapy group, were included, and a meta-analysis was performed using RevMan 5.3 software. The findings revealed that there was no significant difference between the conventional chemotherapy group and the sintilimab group in terms of the overall incidence of adverse drug reactions (ADR) or grade 3–5 ADRs (risk ratio, 1.04; 95% confidence interval, 0.96-1.14; P=0.33), respectively. Sintilimab coupled with chemotherapy outperformed standard chemotherapy in treating advanced NSCLC. The ADRs did not differ considerably from those of conventional chemotherapy, which will help in the assessment of the clinical efficacy of sintilimab combined with chemotherapy and conventional chemotherapy in treating advanced NSCLC.

Use of Chinese Visible Human Images to Enhance the Interpretation of CT or MRI Images: Application to Nasopharyngeal Structures Segmentation in the Treatment Planning System

Background: With leading morbidity among malignant tumors in otorhinolaryngology, Nasopharyngeal carcinoma (NPC) is one of the most frequent malignant tumors in China. Objectives: This study aimed to help radiotherapy doctors recognize and segment nasopharyngeal organs at risk of NPC and make a radiotherapy plan. Methods: The authors used B-spline and mutual information to transform, register, and fuse Chinese Visible Human images with the volunteer’s personalized computed tomography (CT) images, and integrated them into the Treatment Planning System (TPS). Consequently, Three-Dimensional Visualization Treatment Planning System (3DV+TPS) was created. To verify it, 3DV+TPS was deployed to identify and segment the nasopharyngeal organs at risk of NPC, and a questionnaire was filled out by radiotherapy doctors. Results: Results showed that 3DV+TPS can finish the registration and fusion of four sets of sectional anatomical images and individual CT images of volunteers in approximately 3 min and 50 sec. Conclusion: The registered and fused images can accurately reflect the position, outline, and adjacent space of the nasopharyngeal structure which is not clear in CT images. Therefore, it is helpful for recognizing and segmenting neural, muscular, and glandular structures. Through automatically registering and fusing color and CT gray images, 3DV+TPS improves the accuracy and efficiency of recognizing nasopharyngeal structures in making radiotherapy plans. It is also useful to improve the teaching quality of tumor radiotherapy for medical students and interns as well.

Cysteinyl-tRNA Synthetase 1 Promotes Ferroptosis-Induced Cell Death via Regulating GPX4 Expression.

Esophageal squamous cell carcinoma (ESCC) has still been considered to be the most common malignant tumors in China. Emerging evidence indicates that cysteinyl-tRNA synthetase 1 (CARS1) has been considered as a ferroptosis-related gene in ESCC. However, the roles and molecular mechanisms of CARS1 in ferroptosis-induced cell death of ESCC are still largely unknown. In our study, we investigated an aberrantly upregulated gene in ESCC tumor tissues CARS1 significantly inhibited cell proliferation, and the ability of migration and invasion promoted the relative level of MDA and ROS and decreased GPX4 expression level in two ESCC cell lines. Mechanistically, both the ferroptosis inhibitor ferrostatin-1 and its inducer erastin were further used and indicated that CARS1 participated in the ferroptosis-induced cell death. Together, these results revealed that CARS1 has a critical function in the progression of ESCC by promoting ferroptosis-induced cell death.

Expert consensus on the diagnosis and treatment of NTRK gene fusion solid tumors in China.

Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase (NTRK) gene fusions are among the first "tumor agnostic" drugs approved for pan-cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second-generation drugs designed to overcome first-generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and (DNA and/or RNA-based) next-generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first- and second-generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.

Research advances of metabolomics in early diagnosis of hepatocellular carcinoma

Primary liver cancer is the second leading cause of death from malignant tumors in China, and hepatocellular carcinoma (HCC) is the main type. The disease stage at the time of HCC diagnosis largely determines the efficacy of subsequent treatment. Due to the HCC screening among high-risk population has not yet popularized, and the current diagnose method of early HCC is not satisfactory, the early HCC diagnosis rate is less than 30% in China. Metabolomics research emerging in recent years has promoted the research progress of HCC in many fields, such as elaborating the mechanism of occurrence and development, early prevention and diagnosis, exploring drug treatment targets. At the same time, a large number of serum metabolites with excellent sensitivity and specificity were discovered, which made up for the deficiency of traditional serological indicators and helped the early screening and early diagnosis of HCC. This review will summarize the studies on serum metabolomic markers of HCC in recent 5 years, explore the role of metabolomics in the early prediction and diagnosis of HCC and its application prospect.

CircARID1A binds to IGF2BP3 in gastric cancer and promotes cancer proliferation by forming a circARID1A-IGF2BP3-SLC7A5 RNA–protein ternary complex

BackgroundGastric cancer (GC) is one of the most common malignant tumors in China. Circular RNAs (circRNAs) are novel non-coding RNAs with important regulatory roles in cancer progression. IGF2BP3 has been found to play oncogenic roles in various cancers including GC, while the exact mechanism of IGF2BP3 is largely unknown.MethodsThe expression of IGF2BP3 in GC was evaluated by Western Blot and bioinformatics analysis. CircRNA expression profiles were screened via IGF2BP3 RIP-seq in GC. Sanger sequencing, RNase R digestion, nucleo-plasmic separation and RNA-FISH assays were used to detect the existence and expression of circARID1A. RNA ISH assay was employed to test the expression of circARID1A in paraffin-embedded GC tissues. Moreover, the function of circARID1A on cellular proliferation was assessed by CCK-8, plate colony formation, EdU assays and GC xenograft mouse model in vivo. Furthermore, the location or binding of circARID1A, IGF2BP3 protein and SLC7A5 in GC was evaluated by RNA-FISH/IF or RNA pull-down assays.ResultsWe identified a novel circRNA, circARID1A, that can bind to IGF2BP3 protein. CircARID1A was significantly upregulated in GC tissues compared with noncancerous tissues and positively correlated with tumor length, tumor volume, and TNM stage. CircARID1A knockdown inhibited the proliferation of GC cells in vitro and in vivo and circARID1A played an important role in the oncogenic function of IGF2BP3. Mechanistically, circARID1A served as a scaffold to facilitate the interaction between IGF2BP3 and SLC7A5 mRNA, finally increasing SLC7A5 mRNA stability. Additionally, circARID1A was able to directly bind SLC7A5 mRNA through complementary base-pairing and then formed the circARID1A-IGF2BP3-SLC7A5 RNA–protein ternary complex and promoted the proliferation of GC via regulating AKT/mTOR pathway.ConclusionsAltogether, our data suggest that circARID1A is involved in the function of IGF2BP3 and GC proliferation, and the circARID1A-IGF2BP3-SLC7A5 axis has the potential to serve as a novel therapeutic target for GC.

Investigation of the mechanism of the anti-cancer effects of Astragalus propinquus Schischkin and Pinellia pedatisecta Schott (A&P) on melanoma via network pharmacology and experimental verification.

Melanoma is a commonly malignant cutaneous tumor in China. Astragalus propinquus Schischkin and Pinellia pedatisecta Schott (A&P) have been clinically used as adjunctive drugs in the treatment of malignant melanoma. However, the effect and mechanism of A&P on melanoma have yet to be explored. The current investigation seeks to characterize the active components of A&P and their potential roles in treating malignant melanoma using network pharmacology and in vitro and in vivo experiments. We first used the traditional Chinese medicine systems pharmacology (TCMSP) database and high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) to identify a total of 13 effective compounds within A&P. 70 common genes were obtained by matching 487 potential genes of A&P with 464 melanoma-related genes, and then we built up protein-protein interaction (PPI) network of these 70 genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The results revealed that A&P might influence the pathobiology of melanoma through the PI3K/Akt pathway. Molecular docking also confirmed that higher content of ingredients in A&P, including hederagenin, quercetin, beta-sitosterol and stigmasterol, had a strong binding activity (affinity < −5 kcal/mol) with the core targets AKT1, MAPK3 and ESR1. Furthermore, we confirmed A&P could inhibit melanoma cells proliferation and induce cells apoptosis through suppressing the PI3K/Akt signaling pathway by in vitro and in vivo xenograft model experiments. These findings indicate that A&P may function as a useful therapy for melanoma through the PI3K/Akt pathway.